The DOI matches its Crossref record; 37 of the 38 references it cites were found in a registry or an index; 31 of the 69 sources its claims cite were checked for support.
miR-33a/b contribute to the regulation of fatty acid metabolism and insulin signaling
Open accessAbstract
Cellular imbalances of cholesterol and fatty acid metabolism result in pathological processes, including atherosclerosis and metabolic syndrome. Recent work from our group and others has shown that the intronic microRNAs hsa-miR-33a and hsa-miR-33b are located within the sterol regulatory element-binding protein-2 and -1 genes, respectively, and regulate cholesterol homeostasis in concert with their host genes. Here, we show that miR-33a and -b also regulate genes involved in fatty acid metabolism and insulin signaling. miR-33a and -b target key enzymes involved in the regulation of fatty acid oxidation, including carnitine O -octaniltransferase, carnitine palmitoyltransferase 1A, hydroxyacyl-CoA-dehydrogenase, Sirtuin 6 (SIRT6), and AMP kinase subunit-α. Moreover, miR-33a and -b also target the insulin receptor substrate 2, an essential component of the insulin-signaling pathway in the liver. Overexpression of miR-33a and -b reduces both fatty acid oxidation and insulin signaling in hepatic cell lines, whereas inhibition of endogenous miR-33a and -b increases these two metabolic pathways. Together, these data establish that miR-33a and -b regulate pathways controlling three of the risk factors of metabolic syndrome, namely levels of HDL, triglycerides, and insulin signaling, and suggest that inhibitors of miR-33a and -b may be useful in the treatment of this growing health concern.
Overview
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Written from the paper’s full text.
TL;DR
miR-33a and miR-33b, intronic miRNAs of SREBP-2 and SREBP-1, directly target genes involved in fatty acid oxidation and insulin signaling, including CROT, CPT1a, HADHB, AMPKα, SIRT6, and IRS2. Overexpression reduces fatty acid oxidation and insulin signaling in hepatic cells, whereas inhibition increases them, suggesting miR-33 antagonism as a possible therapeutic strategy for metabolic syndrome.
Key findings
- miR-33b repressed luciferase reporters containing the 3′ UTRs of Crot, Cpt1a, Hadhb, Ampkα, Irs2, and Sirt6; mutation of miR-33 target sites relieved repression. In Huh7 cells, miR-33b transfection (32-fold increase) inhibited CROT, CPT1a, HADHB, AMPKα, and IRS2 mRNA, while anti-miR-33b (threefold decrease) increased CROT, CPT1a, AMPKα, and IRS2 mRNA.
- miR-33b overexpression (27-fold increase) reduced [14C]-oleate oxidation in Huh7 cells; anti-miR-33 (2.6-fold increase) increased fatty acid β-oxidation. miR-33b–transfected cells accumulated more triglycerides in larger lipid droplets without changes in basal or insulin-induced triglyceride synthesis. Drosophila fat body miR-33 overexpression caused large lipid droplets and increased TAG upon starvation.
- miR-33b reduced insulin-stimulated AKT and ERK phosphorylation, in vitro AKT kinase activation, and 2-deoxyglucose uptake; IRS2 cDNA lacking the 3′ UTR rescued AKT activation and FoxO1 cytoplasmic translocation. miR-33a and -b differ by 2 nt of 19 nt of the mature RNA but showed similar targeting effects.
- In mice, lentiviral miR-33 reduced hepatic CROT, HADHB, CPT1a, IRS2, and ABCA1 mRNA; anti-miR-33 produced modest increases in CROT, CPT1a, IRS2, and ABCA1 that were not statistically significant.
Methods
- Cell-based assays in Huh7 and HepG2 hepatic cells: luciferase reporter constructs containing wild-type or mutated 3′ UTRs of predicted targets; transfection with miR-33a, miR-33b, anti-miR-33, or controls; mRNA/protein expression and 84-gene arrays for fatty acid and insulin-related genes.
- Metabolic and signaling assays: fatty acid β-oxidation measured by release of [14C]-CO2 from [14C]-oleate; Bodipy staining and triglyceride measurement; insulin-stimulated AKT/ERK phosphorylation, AKT kinase assay, 2-deoxyglucose uptake, and FoxO1-GFP localization.
- In vivo models: mouse lentiviral delivery of premiR-33, anti-miR-33, or control; Drosophila transgenic fat body overexpression of miR-33 with starvation, Bodipy staining, and TAG measurement. Detailed procedures are in SI Materials and Methods.
Limitations
- The paper states that additional experiments, including RIPseq and proteomics, are warranted to understand the miR-33 regulatory network and its implications in lipid and carbohydrate metabolism.
- The paper states that the functional relevance of the miR-33b/SREBP-1 association cannot easily be determined using traditional models of insulin resistance such as rats or mice, because their Srebp1 genes lack miR-33b; it also states that additional research and specialty clinical trials are needed to translate these therapies into clinical practice.
- Evident from the text: much of the mechanistic evidence comes from hepatic cell lines and Drosophila, and the in vivo mouse anti-miR-33 effects on CROT, CPT1a, IRS2, and ABCA1 were modest and not statistically significant.
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Claims the paper makes
48 Own result · 15 Own interpretation · 10 Partly supported · 6 Not checked yet · 4 Supported · 4 Supported so far · 2 No full text of the sources · 2 Own method · 1 No basis given · accuracy not yet measured
Every source the paper cites for this claim was checked and supports it.
In the paper
“In addition to IRS2 and FRS2, our bioinformatic analysis identified a third miR-33 predicted target involved in glucose homeostasis: the histone deacetylase SIRT6 (25, 26).”
What the sources say
- Supportedcites [25] Xiao C, et al. SIRT6 deficiency results in severe hypoglycemia by enhancing both basal and insulin-stimulated glucose uptake in mice. J Biol Chem. 2010;285:36776–36784. doi: 10.1074/jbc.M110.168039. [DOI] [PMC free article] [PubMed] [Google Scholar] source
The Discussion (page not specified) reports that SIRT6 modulates glucose homeostasis: SIRT6-deficient mice had enhanced glucose uptake and severe hypoglycemia. The cited paper supports SIRT6’s role in glucose homeostasis; the miR-33 target prediction is explicitly attributed to the citing authors’ own bioinformatic analysis. (LLM, conf=0.90)
- Supportedcites [26] Zhong L, et al. The histone deacetylase Sirt6 regulates glucose homeostasis via Hif1alpha. Cell. 2010;140:280–293. doi: 10.1016/j.cell.2009.12.041. [DOI] [PMC free article] [PubMed] [Google Scholar] source
The Introduction and Discussion identify SIRT6 as a histone deacetylase that regulates glucose homeostasis. The bioinformatic prediction that SIRT6 is a miR-33 target is the citing authors’ own finding, not a finding attributed to this source. (LLM, conf=0.92)
plaincorrelational- Asserted: passes — The authors put it forward as true.
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In the paper
“Although our previous work in mice supports this contention by showing that inhibition of miR-33a and -b effectively increases HDL (14)”
What the sources say
- Partly supportedcites [14] Rayner KJ, et al. MiR-33 contributes to the regulation of cholesterol homeostasis. Science. 2010;328:1570–1573. doi: 10.1126/science.1189862. [DOI] [PMC free article] [PubMed] [Google Scholar] sourceExperimental — accuracy not yet measured
The passage on the mouse experiment (indexed under Abstract; page unavailable) reports that anti-miR-33 increased plasma HDL by 25% after six days. The paper identifies the studied mouse miR-33 as the homolog of human miR-33a; our copy does not show that inhibition of miR-33b was tested in mice. (LLM, conf=0.89)
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- Partly supported
The sources with a verdict support this claim; the rest weren’t checked yet, have no full text we could read, or their verdicts aren’t rated yet.
In the paper
“Importantly, these pathways regulate circulating HDL levels through their roles in HDL biogenesis and cellular cholesterol efflux (12–14).”
What the sources say
- Not checked — no full text of the sourcecites [12] Marquart TJ, Allen RM, Ory DS, Baldán A. miR-33 links SREBP-2 induction to repression of sterol transporters. Proc Natl Acad Sci USA. 2010;107:12228–12232. doi: 10.1073/pnas.1005191107. [DOI] [PMC free article] [PubMed] [Google Scholar] source
- Supportedcites [13] Najafi-Shoushtari SH, et al. MicroRNA-33 and the SREBP host genes cooperate to control cholesterol homeostasis. Science. 2010;328:1566–1569. doi: 10.1126/science.1189123. [DOI] [PMC free article] [PubMed] [Google Scholar] source
The Results report that inhibiting miR-33 increased cholesterol efflux from macrophages and significantly raised plasma HDL-cholesterol in mice. They also describe ABCA1-dependent cholesterol efflux and HDL biogenesis as parts of the miR-33/SREBP/ABCA1 regulatory circuit. (LLM, conf=0.90)
- Supportedcites [14] Rayner KJ, et al. MiR-33 contributes to the regulation of cholesterol homeostasis. Science. 2010;328:1570–1573. doi: 10.1126/science.1189862. [DOI] [PMC free article] [PubMed] [Google Scholar] source
The passage labeled Abstract explicitly identifies HDL biogenesis in the liver and cellular cholesterol efflux as two pathways that control HDL cholesterol. It also reports that manipulating miR-33 changes circulating HDL levels in mice. (LLM, conf=0.94)
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A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“miR-33a and -b target key enzymes involved in the regulation of fatty acid oxidation, including carnitine O-octaniltransferase, carnitine palmitoyltransferase 1A, hydroxyacyl-CoA-dehydrogenase, Sirtuin 6 (SIRT6), and AMP kinase subunit-α.”
plaindirect- Asserted: passes — The authors put it forward as true.
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None of the sources cited for this claim have been checked yet.
In the paper
“As shown in Fig. S2 (red box), several genes involved in fatty acid β-oxidation have predicted targets for miR-33, including CROT, CPT1a, HADHB and AMPKα (17–20).”
What the sources say
- Not checked yetcites [17] Brady PS, Ramsay RR, Brady LJ. Regulation of the long-chain carnitine acyltransferases. FASEB J. 1993;7:1039–1044. doi: 10.1096/fasebj.7.11.8370473. [DOI] [PubMed] [Google Scholar]
- Not checked — no full text of the sourcecites [18] Eaton S, et al. The mitochondrial trifunctional protein: Centre of a beta-oxidation metabolon? Biochem Soc Trans. 2000;28:177–182. doi: 10.1042/bst0280177. [DOI] [PubMed] [Google Scholar] source
- Not checked — no full text of the sourcecites [19] Mannaerts GP, Van Veldhoven PP, Casteels M. Peroxisomal lipid degradation via beta- and alpha-oxidation in mammals. Cell Biochem Biophys. 2000;32:73–87. doi: 10.1385/cbb:32:1-3:73. [DOI] [PubMed] [Google Scholar] source
- Not checked yetcites [20] Ramsay RR, Gandour RD. Selective modulation of carnitine long-chain acyltransferase activities. Kinetics, inhibitors, and active sites of COT and CPT-II. Adv Exp Med Biol. 1999;466:103–109. [PubMed] [Google Scholar]
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In the paper
“Here, we show that miR-33a and -b also regulate genes involved in fatty acid metabolism and insulin signaling.”
- Also stated in: § Abstract · plain
“In addition to this role in maintaining cholesterol homeostasis, we now show that miR-33a and -b also regulate fatty acid metabolism and insulin signaling.”
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- Rests on an assumption: IRS2 is an essential component of the insulin-signaling pathway in the liver.
- Also stated in: § Abstract · plain
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In the paper
“Kinetic analysis of miR-33b induction revealed a concomitant increase in miR-33b and SREBP-1c expression, consistent with their coregulation.”
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“As shown in Fig. S1 A and B, miR-33b is synchronously expressed with SREBP-1c in human hepatic Huh7 cells treated with an agonist of the liver X receptor (LXR), a transcriptional regulator of Srebp-1c expression.”
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“Moreover, miR-33a and -b also target the insulin receptor substrate 2, an essential component of the insulin-signaling pathway in the liver.”
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“Notably, we show that miR-33a and miR-33b have overlapping gene targets”
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In the paper
“As seen in Fig. 3F, miR-33b overexpression reduced insulin-induced 2-deoxyglucose (2-DOG) uptake in Huh7 cells.”
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“We now show that a second member of the miR-33 family, miR-33b, is coregulated with the human Srebp1 gene and targets genes involved in fatty acid oxidation and insulin signaling.”
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“Conversely, mice expressing anti–miR-33 showed a modest increase of CROT, CPT1a, IRS2, and ABCA1 mRNA expression, although the effect was not statistically significant (Fig. S4).”
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“As expected, IRS2 was down-regulated in Huh7 cells transfected with miR-33b (Fig. 3D).”
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“In agreement with the reduced fatty acid β-oxidation rates observed in hepatic cells overexpressing miR-33b, Huh7 cells transfected with miR-33b accumulated more triglycerides (TAG) in larger lipid droplets (Fig. 2 C and D).”
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“As seen in Fig. 2E, miR-33 expression did not alter basal and insulin-induced triglyceride synthesis.”
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“Similarly, flies overexpressing miR-33 accumulated more TAG upon starvation (Fig. 2H), indicating that the function of miR-33 in regulating fatty acid oxidation is conserved from Drosophila to humans.”
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“We now show that a second member of the miR-33 family, miR-33b, is coregulated with the human Srebp1 gene and targets genes involved in fatty acid oxidation and insulin signaling.”
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“Consistent with our in vitro results, miR-33 reduced hepatic CROT, HADHB, CPT1a, IRS2, and ABCA1 mRNA expression (Fig. S4).”
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“miR-33b markedly repressed the 3′ UTR activity of Sirt6 (Fig. S8A)”
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“mutation of the miR-33 target sites in the 3′ UTR relieved miR-33b repression of Sirt6”
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“Furthermore, miR-33b overexpression significantly inhibited the SIRT6 mRNA and protein levels in Huh7 cells (Fig. S8 B and C)”
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“Interestingly, IRS2 overexpression rescued the effect of miR-33 overexpression on FoxO1 intracellular localization (Fig. S7 C and D).”
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“miR-33b overexpression (27-fold increase) markedly reduced the fatty acid β-oxidation in Huh7 (Fig. 2A) cells.”
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“In addition, both miR-33a and -b significantly inhibited the 3′ UTR activity of Crot, Cpt1a, Hadhb, Ampkα, and Irs2 with only modest differences, indicating that the 2-nt variation in the mature forms of miR-33a and -b does not appreciably affect the gene targeting by these miRNAs.”
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“As seen in Fig. S6, miR-33a and -b inhibited CROT, CPT1a, HADHB, AMPKα, SIRT6, and IRS2 protein expression to a similar extent.”
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“As seen in Fig. 3 D and E, IRS2 expression rescued the AKT activation on insulin stimulation in miR-33b–overexpressing cells.”
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“Mutation of both miR-33 sites in the 3′ UTR of Crot was necessary to completely reverse the inhibitory effects of miR-33 (Fig. S3).”
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“As seen in Fig. 3 A and B, Huh7 cells transfected with miR-33b showed reduced AKT and ERK phosphorylation after insulin stimulation”
- Also stated in: § Results · plain
“Similar results were observed when we analyzed the AKT activation using an in vitro kinase assay (Fig. 3C).”
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“Transfection of Huh7 cells with miR-33b (32-fold increase expression) significantly inhibited the mRNA levels of CROT, CPT1a, HADHB, AMPKα, and IRS2 (Fig. 1A).”
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“Notably, inhibition of endogenous miR-33b using anti–miR-33b oligonucleotides (threefold decrease expression) increased the mRNA expression of CROT, CPT1a, AMPKα, and IRS2 in Huh7 cells (Fig. 1B), consistent with a physiological role for miR-33b in regulating the expression of these genes.”
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“miR-33b markedly repressed the activity of the Crot, Cpt1a, Hadhb, Ampkα, and Irs2 3′ UTR luciferase constructs (Fig. S3).”
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“Accordingly, fat bodies from starved miR-33 transgenic flies, dissected and stained with Bodipy, showed large lipid droplets in many cells compared with control flies (Fig. 2G).”
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“because inhibition of SIRT6 expression by siRNA only modestly decreased fatty acid β-oxidation (Fig. S8D).”
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“As seen in Fig. 3 A and B, Huh7 cells transfected with miR-33b showed reduced AKT and ERK phosphorylation after insulin stimulation”
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“Conversely, inhibition of endogenous miR-33b expression using anti–miR-33 (2.6-fold increase) increased the rate of fatty acid β-oxidation (Fig. 2B).”
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“whereas inhibition of endogenous miR-33b by anti–miR-33 increased the expression of SIRT6 (Fig. S8 B and C).”
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A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“The increase in triglyceride content was independent of changes in triglyceride synthesis rates.”
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Finally, we show that miR-33 transgenic flies show increased lipid accumulation in tissues”
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Importantly, we show that miR-33 overexpression reduces fatty acid oxidation in hepatic cell lines.”
boosteddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“our bioinformatic analysis of miR-33a and -b target genes revealed an enrichment of genes involved in fatty acid metabolism.”
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“We identify herein six miR-33 target genes that regulate fatty acid metabolism and insulin signaling, including CPT1a, CROT, HADHB, AMPKα, SIRT6, and IRS2.”
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
None of the sources cited for this claim have been checked yet.
In the paper
“Together, these data establish that miR-33a and -b regulate pathways controlling three of the risk factors of metabolic syndrome, namely levels of HDL, triglycerides, and insulin signaling”
- Also stated in: § Abstract · hedged
“Together, these data suggest that feedback loops involving SREBPs and miR-33a and -b balance cholesterol metabolism, fatty acid oxidation, and insulin signaling, three of the major risk factors of metabolic syndrome (1, 3, 15).”
What the sources say
- Not checked — no full text of the sourcecites [1] Alberti KG, Zimmet P, Shaw J. Metabolic syndrome—a new world-wide definition. A Consensus Statement from the International Diabetes Federation. Diabet Med. 2006;23:469–480. doi: 10.1111/j.1464-5491.2006.01858.x. [DOI] [PubMed] [Google Scholar] source
- Not checked yetcites [3] Hotamisligil GS. Inflammation and metabolic disorders. Nature. 2006;444:860–867. doi: 10.1038/nature05485. [DOI] [PubMed] [Google Scholar]
- Not checked — no full text of the sourcecites [15] Terán-García M, Bouchard C. Genetics of the metabolic syndrome. Appl Physiol Nutr Metab. 2007;32:89–114. doi: 10.1139/h06-102. [DOI] [PubMed] [Google Scholar] source
boosteddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Rests on an assumption: IRS2 is an essential component of the insulin-signaling pathway in the liver.
- Also stated in: § Abstract · hedged
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Together, these results suggest a paradigm in which miR-33a and miR-33b act in concert with their host genes, Srebp-2 and Srebp-1, to boost intracellular cholesterol and fatty acid levels by balancing transcriptional induction and posttranscriptional repression of lipid metabolism genes.”
hedgeddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Together, these experiments identify miR-33 as an important regulator of the insulin-signaling pathways.”
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“consistent with a direct interaction of miR-33b with these sites (Fig. S8A)”
hedgedcorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“indicating that the function of miR-33 in regulating fatty acid oxidation is conserved from Drosophila to humans.”
hedgeddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“this is unlikely to contribute to the regulation of fatty acid metabolism by miR-33b”
hedged- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“As seen in Fig. 3 A and B, Huh7 cells transfected with miR-33b showed reduced AKT and ERK phosphorylation after insulin stimulation, indicative of reduced IRS2 function.”
hedgeddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“indicating that the 2-nt variation in the mature forms of miR-33a and -b does not appreciably affect the gene targeting by these miRNAs.”
hedged- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Our data indicate that miR-33a and -b impact pathways influencing three of the primary risk factors in this disease, namely insulin resistance, low HDL, and high triglycerides/VLDL.”
hedgeddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“suggesting that miR-33 regulation of fatty acid metabolism pathways is evolutionarily conserved.”
hedgeddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“By inhibiting expression of IRS2 in hepatic cells, miR-33a and -b reduce the activation of downstream insulin signaling pathways, including AKT and ERK.”
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Our results suggest that antagonism of endogenous miR-33 may be useful as a therapeutic strategy for treating metabolic syndrome and nonalcoholic fatty liver disease (NAFLD)”
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“this establishes a model of reciprocal regulation of cholesterol and fatty acid metabolism by SREBPs (Fig. 4).”
boosteddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“suggesting that cotranscription of Srebp-2 and miR-33a or Srebp-1 and miR-33b would be predicted to regulate both cholesterol metabolism and fatty acid oxidation”
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Our work also identifies miR-33a and -b as regulators of insulin signaling.”
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Probably not a substantial claim. 23
- It may state two separate claims as one. 20
The sources with a verdict support this claim; the rest weren’t checked yet, have no full text we could read, or their verdicts aren’t rated yet.
In the paper
“a class of noncoding RNAs, termed microRNAs (miRNAs), has emerged as critical regulators of gene expression acting predominantly at the posttranscriptional level (8–10).”
What the sources say
- Not checked — no full text of the sourcecites [8] Ambros V. The functions of animal microRNAs. Nature. 2004;431:350–355. doi: 10.1038/nature02871. [DOI] [PubMed] [Google Scholar] source
- Supportedcites [9] Bartel DP. MicroRNAs: Target recognition and regulatory functions. Cell. 2009;136:215–233. doi: 10.1016/j.cell.2009.01.002. [DOI] [PMC free article] [PubMed] [Google Scholar] source
The Abstract describes miRNAs as having important gene-regulatory roles through posttranscriptional repression of mRNAs. The section “The miRNAs” further explains that they commonly repress translation, destabilize mRNAs, or both. (LLM, conf=0.94)
- Not checked — no full text of the sourcecites [10] Filipowicz W, Bhattacharyya SN, Sonenberg N. Mechanisms of post-transcriptional regulation by microRNAs: Are the answers in sight? Nat Rev Genet. 2008;9:102–114. doi: 10.1038/nrg2290. [DOI] [PubMed] [Google Scholar] source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“In mice, however, there is only one miR-33 gene, which is conserved with human miR-33a and located within intron 15 of the mouse Srebp-2 gene.”
What the sources say
- Partly supportedcites [11] Gerin I, et al. Expression of miR-33 from an SREBP2 intron inhibits cholesterol export and fatty acid oxidation. J Biol Chem. 2010;285:33652–33661. doi: 10.1074/jbc.M110.152090. [DOI] [PMC free article] [PubMed] [Google Scholar] sourceExperimental — accuracy not yet measured
The section “miR-33a Is Produced from an Intron of the SREBP2 Gene” says that mice possess miR-33a in SREBP2 but lack miR-33b, and describes miR-33a as highly conserved. It does not specify that the mouse sequence is in intron 15, so that part of the claim is unsupported by our copy. (LLM, conf=0.88)
- Not checked — no full text of the sourcecites [12] Marquart TJ, Allen RM, Ory DS, Baldán A. miR-33 links SREBP-2 induction to repression of sterol transporters. Proc Natl Acad Sci USA. 2010;107:12228–12232. doi: 10.1073/pnas.1005191107. [DOI] [PMC free article] [PubMed] [Google Scholar] source
- Supportedcites [13] Najafi-Shoushtari SH, et al. MicroRNA-33 and the SREBP host genes cooperate to control cholesterol homeostasis. Science. 2010;328:1566–1569. doi: 10.1126/science.1189123. [DOI] [PMC free article] [PubMed] [Google Scholar] source
The Results passage [1] explicitly says that mice have only one miR-33 isoform, conserved with human miR-33a, located in intron 15 of the mouse SREBP-2 gene. This matches the attributed claim. (LLM, conf=0.95)
- Partly supportedcites [14] Rayner KJ, et al. MiR-33 contributes to the regulation of cholesterol homeostasis. Science. 2010;328:1570–1573. doi: 10.1126/science.1189862. [DOI] [PMC free article] [PubMed] [Google Scholar] sourceExperimental — accuracy not yet measured
The sequence-alignment passage (indexed under Abstract; page unavailable) identifies mouse mmu-miR-33 as the homolog of human miR-33a and places it in SREBF2. It specifies intron 16, not intron 15, and does not establish that mice have only one miR-33 gene. (LLM, conf=0.90)
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
- Partly supported
The sources with a verdict support this claim; the rest weren’t checked yet, have no full text we could read, or their verdicts aren’t rated yet.
In the paper
“SREBP-1c regulates the transcription of genes involved in fatty acid metabolism, such as fatty acid synthase (FASN) (5–7).”
What the sources say
- Not checked — no full text of the sourcecites [5] Brown MS, Goldstein JL. The SREBP pathway: Regulation of cholesterol metabolism by proteolysis of a membrane-bound transcription factor. Cell. 1997;89:331–340. doi: 10.1016/s0092-8674(00)80213-5. [DOI] [PubMed] [Google Scholar] source
- Supportedcites [6] Horton JD, Goldstein JL, Brown MS. SREBPs: Activators of the complete program of cholesterol and fatty acid synthesis in the liver. J Clin Invest. 2002;109:1125–1131. doi: 10.1172/JCI15593. [DOI] [PMC free article] [PubMed] [Google Scholar] source
The section “SREBPs: two genes, three proteins” identifies fatty acid synthase (FASN) among SREBP-1c-responsive genes in the fatty acid biosynthetic pathway. The “SREBPs in liver: unanswered questions” section also discusses transcriptional activation of FASN in concert with SREBPs. (LLM, conf=0.94)
- Supportedcites [7] Osborne TF. Sterol regulatory element-binding proteins (SREBPs): Key regulators of nutritional homeostasis and insulin action. J Biol Chem. 2000;275:32379–32382. doi: 10.1074/jbc.R000017200. [DOI] [PubMed] [Google Scholar] source
In “Key Role for SREBPs in Insulin Action and Lipogenesis” (page not available), the paper calls SREBP-1c a key transcriptional activator of lipogenesis and reports that blocking it prevented induction of FAS mRNA. This supports the claim that SREBP-1c regulates expression of fatty-acid-metabolism genes, including fatty acid synthase. (LLM, conf=0.92)
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“SREBP-2 regulates the transcription of cholesterol-related genes, such as 3-hydroxy-3-methylglutaryl CoA reductase (HMGCR), which catalyzes a rate-limiting step in cholesterol biosynthesis, and the low-density lipoprotein receptor (LDLr), which imports cholesterol from the blood (5–7).”
What the sources say
- Not checked — no full text of the sourcecites [5] Brown MS, Goldstein JL. The SREBP pathway: Regulation of cholesterol metabolism by proteolysis of a membrane-bound transcription factor. Cell. 1997;89:331–340. doi: 10.1016/s0092-8674(00)80213-5. [DOI] [PubMed] [Google Scholar] source
- Supportedcites [6] Horton JD, Goldstein JL, Brown MS. SREBPs: Activators of the complete program of cholesterol and fatty acid synthesis in the liver. J Clin Invest. 2002;109:1125–1131. doi: 10.1172/JCI15593. [DOI] [PMC free article] [PubMed] [Google Scholar] source
In “SREBPs: two genes, three proteins,” the review identifies HMG-CoA reductase as an SREBP-2-responsive cholesterol-biosynthesis gene. “Function of individual SREBP isoforms in vivo” states that SREBP-2 preferentially activates the LDL receptor gene and genes required for cholesterol synthesis. Page numbers are not provided in our copy. (LLM, conf=0.94)
- Partly supportedcites [7] Osborne TF. Sterol regulatory element-binding proteins (SREBPs): Key regulators of nutritional homeostasis and insulin action. J Biol Chem. 2000;275:32379–32382. doi: 10.1074/jbc.R000017200. [DOI] [PubMed] [Google Scholar] sourceExperimental — accuracy not yet measured
The section “Selective Roles for Individual SREBP Isoforms in Either Cholesterol or Fatty Acid Metabolism” says SREBP-2 may preferentially activate genes involved in cholesterol homeostasis, supporting the general point. The passages do not identify HMGCR or LDLr as SREBP-2 transcriptional targets; the specific LDL-receptor expression example instead concerns SREBP-1a. Page numbers are unavailable in our copy. (LLM, conf=0.84)
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“We and others provided identification of a highly conserved miRNA family, miR-33, within the intronic sequences of the Srebp genes in organisms ranging from Drosophila to humans (11–14).”
What the sources say
- Supportedcites [11] Gerin I, et al. Expression of miR-33 from an SREBP2 intron inhibits cholesterol export and fatty acid oxidation. J Biol Chem. 2010;285:33652–33661. doi: 10.1074/jbc.M110.152090. [DOI] [PMC free article] [PubMed] [Google Scholar] source
The section “miR-33a Is Produced from an Intron of the SREBP2 Gene” places miR-33a and miR-33b in introns of the human SREBP genes and says the family's location and sequence are highly conserved down to insects. The section on Drosophila CPT1 explicitly identifies miR-33 as highly conserved in Drosophila. (LLM, conf=0.93)
- Not checked — no full text of the sourcecites [12] Marquart TJ, Allen RM, Ory DS, Baldán A. miR-33 links SREBP-2 induction to repression of sterol transporters. Proc Natl Acad Sci USA. 2010;107:12228–12232. doi: 10.1073/pnas.1005191107. [DOI] [PMC free article] [PubMed] [Google Scholar] source
- Supportedcites [13] Najafi-Shoushtari SH, et al. MicroRNA-33 and the SREBP host genes cooperate to control cholesterol homeostasis. Science. 2010;328:1566–1569. doi: 10.1126/science.1189123. [DOI] [PMC free article] [PubMed] [Google Scholar] source
The Results passage states that the authors noted a highly conserved miR-33 family within intronic sequences of SREBP genes in organisms from Drosophila to humans. It also identifies the introns containing the two human isoforms. (LLM, conf=0.95)
- Partly supportedcites [14] Rayner KJ, et al. MiR-33 contributes to the regulation of cholesterol homeostasis. Science. 2010;328:1570–1573. doi: 10.1126/science.1189862. [DOI] [PMC free article] [PubMed] [Google Scholar] sourceExperimental — accuracy not yet measured
The passage on sequence alignment (section labeled Abstract; page unavailable) identifies human and mouse miR-33 within an intron of SREBF2 and says its precursor is highly conserved in mammals. Our copy does not establish a miR-33 family within Srebp genes across organisms ranging from Drosophila to humans. (LLM, conf=0.87)
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
- Supported
The sources with a verdict support this claim; the rest weren’t checked yet, have no full text we could read, or their verdicts aren’t rated yet.
In the paper
“miRNA targeting of mRNAs inhibits their expression through mRNA destabilization, repression of translation, or a combination of both processes (8–10).”
What the sources say
- Not checked — no full text of the sourcecites [8] Ambros V. The functions of animal microRNAs. Nature. 2004;431:350–355. doi: 10.1038/nature02871. [DOI] [PubMed] [Google Scholar] source
- Supportedcites [9] Bartel DP. MicroRNAs: Target recognition and regulatory functions. Cell. 2009;136:215–233. doi: 10.1016/j.cell.2009.01.002. [DOI] [PMC free article] [PubMed] [Google Scholar] source
The section “The miRNAs” directly states that miRNAs pair with mRNAs to direct posttranscriptional repression and, more commonly, cause translational repression, mRNA destabilization, or both. This matches the claim. (LLM, conf=0.95)
- Not checked — no full text of the sourcecites [10] Filipowicz W, Bhattacharyya SN, Sonenberg N. Mechanisms of post-transcriptional regulation by microRNAs: Are the answers in sight? Nat Rev Genet. 2008;9:102–114. doi: 10.1038/nrg2290. [DOI] [PubMed] [Google Scholar] source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“We recently showed that miR-33a is cotranscribed with its host gene Srebp-2 like many intronic miRNAs, and it targets genes involved in cholesterol export, including the adenosine triphosphate binding cassette (ABC) transporters ABCA1 and ABCG1 and the endolysosomal transport protein Niemann-Pick C1 (NPC1) (14).”
What the sources say
- Partly supportedcites [14] Rayner KJ, et al. MiR-33 contributes to the regulation of cholesterol homeostasis. Science. 2010;328:1570–1573. doi: 10.1126/science.1189862. [DOI] [PMC free article] [PubMed] [Google Scholar] sourceExperimental — accuracy not yet measured
The copy identifies hsa-miR-33a within an intron of SREBF2 and describes coincident transcription of SREBF2 and miR-33 (passages 8 and 7, labeled Abstract). It supports ABCA1 and NPC1 as targets, but explicitly limits ABCG1 targeting to mice; the unqualified claim that miR-33a targets ABCG1 omits that species restriction (passages 3–4, labeled Abstract). (LLM, conf=0.87)
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Partly supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“Two miR-33 genes are present in humans: miR-33b, which is present in intron 17 of the Srebp-1 gene on chromosome 17, and miR-33a, which is located in intron 16 of the Srebp-2 gene on chromosome 22.”
What the sources say
- Partly supportedcites [11] Gerin I, et al. Expression of miR-33 from an SREBP2 intron inhibits cholesterol export and fatty acid oxidation. J Biol Chem. 2010;285:33652–33661. doi: 10.1074/jbc.M110.152090. [DOI] [PMC free article] [PubMed] [Google Scholar] sourceExperimental — accuracy not yet measured
The section “miR-33a Is Produced from an Intron of the SREBP2 Gene” states that human miR-33a and miR-33b lie in introns of SREBP2 and SREBP1, respectively. Our copy does not give the claimed intron numbers or chromosome numbers, so those details are not supported by this source. (LLM, conf=0.86)
- Not checked — no full text of the sourcecites [12] Marquart TJ, Allen RM, Ory DS, Baldán A. miR-33 links SREBP-2 induction to repression of sterol transporters. Proc Natl Acad Sci USA. 2010;107:12228–12232. doi: 10.1073/pnas.1005191107. [DOI] [PMC free article] [PubMed] [Google Scholar] source
- Partly supportedcites [13] Najafi-Shoushtari SH, et al. MicroRNA-33 and the SREBP host genes cooperate to control cholesterol homeostasis. Science. 2010;328:1566–1569. doi: 10.1126/science.1189123. [DOI] [PMC free article] [PubMed] [Google Scholar] sourceExperimental — accuracy not yet measured
The Results identify two human miR-33 isoforms and place miR-33b in intron 17 of SREBP-1 on chromosome 17. They place miR-33a in intron 15 of SREBP-2 on chromosome 22, not intron 16 as the citing sentence states. (LLM, conf=0.95)
- Partly supportedcites [14] Rayner KJ, et al. MiR-33 contributes to the regulation of cholesterol homeostasis. Science. 2010;328:1570–1573. doi: 10.1126/science.1189862. [DOI] [PMC free article] [PubMed] [Google Scholar] sourceExperimental — accuracy not yet measured
The passage labeled Abstract (page not supplied) identifies human miR-33a within intron 16 of SREBF2. Our copy does not state the chromosome 22 location or identify miR-33b in SREBF1 on chromosome 17, so it supports only part of the attributed sentence. (LLM, conf=0.87)
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
- Partly supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“SIRT6-deficient mice develop normally but succumb to lethal hypoglycemia early in life, suggesting an important role of SIRT6 in regulating glucose metabolism (25, 26).”
What the sources say
- Partly supportedcites [25] Xiao C, et al. SIRT6 deficiency results in severe hypoglycemia by enhancing both basal and insulin-stimulated glucose uptake in mice. J Biol Chem. 2010;285:36776–36784. doi: 10.1074/jbc.M110.168039. [DOI] [PMC free article] [PubMed] [Google Scholar] sourceExperimental — accuracy not yet measured
The Results section reports that SIRT6-deficient mice were born without obvious defects, but weighed less from postnatal day 3 and developed other abnormalities; it does not support saying they developed normally. The Abstract and Results support early hypoglycemia-related deaths in many mutants and a role for SIRT6 in glucose metabolism, although some survived beyond the early post-weaning period. Page numbers are unavailable in our copy. (LLM, conf=0.88)
- Supportedcites [26] Zhong L, et al. The histone deacetylase Sirt6 regulates glucose homeostasis via Hif1alpha. Cell. 2010;140:280–293. doi: 10.1016/j.cell.2009.12.041. [DOI] [PMC free article] [PubMed] [Google Scholar] source
The Abstract (page unavailable) states that SIRT6-deficient mice develop normally but die from lethal hypoglycemia early in life. The Results section on glucose uptake and the Discussion (pages unavailable) also describe the lethal hypoglycemia and SIRT6’s role in glucose homeostasis. (LLM, conf=0.95)
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. It may state two separate claims as one.
- Partly supported
Every source the paper cites for this claim was checked and supports it.
In the paper
“Interestingly, it has also been recently reported that hepatic-specific disruption of SIRT6 in mice results in fatty liver formation because of enhanced glycolysis and triglyceride synthesis (27).”
What the sources say
- Supportedcites [27] Kim HS, et al. Hepatic-specific disruption of SIRT6 in mice results in fatty liver formation due to enhanced glycolysis and triglyceride synthesis. Cell Metab. 2010;12:224–236. doi: 10.1016/j.cmet.2010.06.009. [DOI] [PMC free article] [PubMed] [Google Scholar] source
The Abstract states that liver-specific deletion of SIRT6 in mice increases glycolysis and triglyceride synthesis and leads to fatty liver formation. The Discussion likewise identifies these changes as contributors to fatty liver, alongside other metabolic changes. (LLM, conf=0.95)
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
- Supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“IRS2 is a cytoplasmic signaling molecule that mediates the effects of insulin, insulin-like growth factor 1, and other cytokines by acting as a molecular adaptor between receptor tyrosine kinases and downstream effectors (21–23).”
What the sources say
- Partly supportedcites [21] Haeusler RA, Accili D. The double life of Irs. Cell Metab. 2008;8:7–9. doi: 10.1016/j.cmet.2008.06.010. [DOI] [PMC free article] [PubMed] [Google Scholar] sourceExperimental — accuracy not yet measured
The paper’s opening passage describes Irs1 and Irs2 as insulin-signaling adaptors that act downstream of insulin and IGF receptors to engage other signaling components. The Liver Conundrum section also describes Irs2 mediating insulin action. Our copy does not establish the claim’s additional assertion that Irs2 mediates the effects of other cytokines. (LLM, conf=0.86)
- Not checked — no full text of the sourcecites [22] Thirone AC, Huang C, Klip A. Tissue-specific roles of IRS proteins in insulin signaling and glucose transport. Trends Endocrinol Metab. 2006;17:72–78. doi: 10.1016/j.tem.2006.01.005. [DOI] [PubMed] [Google Scholar] source
- Not checked — no full text of the sourcecites [23] White MF. IRS proteins and the common path to diabetes. Am J Physiol Endocrinol Metab. 2002;283:E413–E422. doi: 10.1152/ajpendo.00514.2001. [DOI] [PubMed] [Google Scholar] source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim.
- Partly supported
Every source the paper cites for this claim was checked and supports it.
In the paper
“Although our previous work established that miR-33a and Srebp-2 are cotranscribed during states of cholesterol depletion (14)”
What the sources say
- Supportedcites [14] Rayner KJ, et al. MiR-33 contributes to the regulation of cholesterol homeostasis. Science. 2010;328:1570–1573. doi: 10.1126/science.1189862. [DOI] [PMC free article] [PubMed] [Google Scholar] source
The paper identifies miR-33a as the human homolog of the mouse miR-33 it studies. It reports that cholesterol-depleted macrophages up-regulate both miR-33 and SREBF2, and explicitly describes their coincident transcription under low-sterol conditions (passages labeled Abstract; no page numbers supplied). (LLM, conf=0.93)
boostedcorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
- Supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“We and others have recently established that, during sterol-limited states, miR-33a is coincidentally generated with Srebp-2 transcription and works to increase cellular cholesterol levels by limiting cholesterol export through the down-regulation of ABC transporters, ABCA1 and ABCG1 (12–14).”
What the sources say
- Not checked — no full text of the sourcecites [12] Marquart TJ, Allen RM, Ory DS, Baldán A. miR-33 links SREBP-2 induction to repression of sterol transporters. Proc Natl Acad Sci USA. 2010;107:12228–12232. doi: 10.1073/pnas.1005191107. [DOI] [PMC free article] [PubMed] [Google Scholar] source
- Partly supportedcites [13] Najafi-Shoushtari SH, et al. MicroRNA-33 and the SREBP host genes cooperate to control cholesterol homeostasis. Science. 2010;328:1566–1569. doi: 10.1126/science.1189123. [DOI] [PMC free article] [PubMed] [Google Scholar] sourceExperimental — accuracy not yet measured
The Results report that cholesterol depletion increased both miR-33a and its SREBP-2 host gene in mouse macrophages, while reducing ABCA1 protein. They also show that miR-33a reduced cholesterol efflux and promoted intracellular cholesterol retention through ABCA1 repression. The passages do not support the additional claim that miR-33a down-regulates ABCG1. (LLM, conf=0.88)
- Partly supportedcites [14] Rayner KJ, et al. MiR-33 contributes to the regulation of cholesterol homeostasis. Science. 2010;328:1570–1573. doi: 10.1126/science.1189862. [DOI] [PMC free article] [PubMed] [Google Scholar] sourceExperimental — accuracy not yet measured
The passages labeled Abstract report that miR-33 rises alongside SREBF2 during cholesterol depletion and represses cholesterol export through ABCA1. They also show ABCG1 repression in mouse cells, but state that human ABCG1 lacks miR-33 binding sites. The claim does not qualify its ABCG1 statement by species, despite referring specifically to miR-33a. (LLM, conf=0.88)
boosteddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
Every source the paper cites for this claim was checked and supports it.
In the paper
“Although our previous work established that miR-33a and Srebp-2 are cotranscribed during states of cholesterol depletion (14), the changes in Srebp-2 and miR-33a transcription were quite small in this setting.”
What the sources say
- Supportedcites [14] Rayner KJ, et al. MiR-33 contributes to the regulation of cholesterol homeostasis. Science. 2010;328:1570–1573. doi: 10.1126/science.1189862. [DOI] [PMC free article] [PubMed] [Google Scholar] source
The citation is attached to the statement that miR-33a and SREBF2 are cotranscribed during cholesterol depletion, not to the subsequent statement that their transcriptional changes were small. The passage labeled Abstract reports concomitant induction under cholesterol depletion, consistent with coregulation; it describes that increase as robust. The citing authors’ characterization of the changes as small is therefore not supported by this source, but is not the claim the citation is attached to. (LLM, conf=0.91)
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
- Supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“By contrast, Srebp-1c is transcribed at extremely high levels in response to insulin (6, 28)”
What the sources say
- Partly supportedcites [6] Horton JD, Goldstein JL, Brown MS. SREBPs: Activators of the complete program of cholesterol and fatty acid synthesis in the liver. J Clin Invest. 2002;109:1125–1131. doi: 10.1172/JCI15593. [DOI] [PMC free article] [PubMed] [Google Scholar] sourceExperimental — accuracy not yet measured
The sections “Transcriptional regulation of SREBP genes” and “SREBP-1c and the insulin/glucagon ratio” say that insulin regulates SREBP-1c transcription and increases its mRNA in rat hepatocytes. They do not establish that it is transcribed at “extremely high levels”; no page number is available in our copy. (LLM, conf=0.86)
- Supportedcites [28] Brown MS, Ye J, Goldstein JL. Medicine. HDL miR-ed down by SREBP introns. Science. 2010;328:1495–1496. doi: 10.1126/science.1192409. [DOI] [PMC free article] [PubMed] [Google Scholar] source
The passage labeled Abstract states that insulin enhances SREBP-1c transcription in the liver and that, when insulin levels are high, it is transcribed at extremely high levels. This directly supports the attributed claim in its hepatic context. (LLM, conf=0.94)
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
- Partly supported
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Overexpression of miR-33a and -b reduces both fatty acid oxidation and insulin signaling in hepatic cell lines”
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Rests on an assumption: IRS2 is an essential component of the insulin-signaling pathway in the liver.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“whereas inhibition of endogenous miR-33a and -b increases these two metabolic pathways.”
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Rests on an assumption: IRS2 is an essential component of the insulin-signaling pathway in the liver.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Similar regulation of these genes by miR-33b was also seen at the protein level (Fig. 1 C and D).”
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Whereas CROT, CPT1a, and AMPKα were predictably down-regulated by miR-33, we did not observe changes in the expression of non–miR-33 targets (Fig. 1E).”
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Interestingly, FRS2 is also a predicted target of miR-33a and -b.”
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Moreover, glucokinase (GCK), fibroblast growth factor receptor substrate 2 (FRS2), acetyl-CoA carboxylase-α (ACACA), and peroxisome proliferator-activated–γ (PPARG) were also inhibited (Fig. 3D).”
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Furthermore, other genes containing putative miR-33 binding sites such as citrate synthase (CS) and HMGCR were not affected either at the mRNA level (Fig. S5A) or by 3′ UTR activity (Fig. S5B).”
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Furthermore, mutation of the miR-33 target sites in these constructs relieved miR-33b repression of the 3′ UTR of Crot, Cpt1a, Hadhb, Ampkα, and Irs2, consistent with a direct interaction of miR-33b with these sites (Fig. S3).”
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Treatment with insulin induced FoxO1-GFP translocation from the nucleus to the cytoplasm in Con-miR–transfected cells (Fig. S7A Lower), whereas cells transfected with miR-33b had the cellular distribution reversed (Fig. S7B Lower).”
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Importantly, we show that antagonism of endogenous miR-33a and -b up-regulates fatty acid oxidation and response to insulin in hepatocytes”
boosteddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“FoxO1 is a well-defined target downstream of the conserved insulin/target of rapamycin (TOR) signaling network that has important roles in the regulation of processes as diverse as cellular growth, stress resistance, and energy homeostasis (24).”
What the sources say
- Not checked — no full text of the sourcecites [24] Accili D, Arden KC. FoxOs at the crossroads of cellular metabolism, differentiation, and transformation. Cell. 2004;117:421–426. doi: 10.1016/s0092-8674(04)00452-0. [DOI] [PubMed] [Google Scholar] source
boosteddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“CROT, a carnitine acyltransferase that catalyzes the reversible transfer of fatty acyl between CoA and carnitine, provides a crucial step in the transport of medium and long-chain acyl-CoA out of the mammalian peroxisome to the cytosol and mitochondria (17–20).”
What the sources say
- Not checked — no full text of the sourcecites [17] Brady PS, Ramsay RR, Brady LJ. Regulation of the long-chain carnitine acyltransferases. FASEB J. 1993;7:1039–1044. doi: 10.1096/fasebj.7.11.8370473. [DOI] [PubMed] [Google Scholar] source
- Not checked — no full text of the sourcecites [18] Eaton S, et al. The mitochondrial trifunctional protein: Centre of a beta-oxidation metabolon? Biochem Soc Trans. 2000;28:177–182. doi: 10.1042/bst0280177. [DOI] [PubMed] [Google Scholar] source
- Not checked — no full text of the sourcecites [19] Mannaerts GP, Van Veldhoven PP, Casteels M. Peroxisomal lipid degradation via beta- and alpha-oxidation in mammals. Cell Biochem Biophys. 2000;32:73–87. doi: 10.1385/cbb:32:1-3:73. [DOI] [PubMed] [Google Scholar] source
- Not checked yetcites [20] Ramsay RR, Gandour RD. Selective modulation of carnitine long-chain acyltransferase activities. Kinetics, inhibitors, and active sites of COT and CPT-II. Adv Exp Med Biol. 1999;466:103–109. [PubMed] [Google Scholar]
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“AMPKα stimulates hepatic fatty acid oxidation and ketogenesis (17–20).”
What the sources say
- Not checked — no full text of the sourcecites [17] Brady PS, Ramsay RR, Brady LJ. Regulation of the long-chain carnitine acyltransferases. FASEB J. 1993;7:1039–1044. doi: 10.1096/fasebj.7.11.8370473. [DOI] [PubMed] [Google Scholar] source
- Not checked — no full text of the sourcecites [18] Eaton S, et al. The mitochondrial trifunctional protein: Centre of a beta-oxidation metabolon? Biochem Soc Trans. 2000;28:177–182. doi: 10.1042/bst0280177. [DOI] [PubMed] [Google Scholar] source
- Not checked — no full text of the sourcecites [19] Mannaerts GP, Van Veldhoven PP, Casteels M. Peroxisomal lipid degradation via beta- and alpha-oxidation in mammals. Cell Biochem Biophys. 2000;32:73–87. doi: 10.1385/cbb:32:1-3:73. [DOI] [PubMed] [Google Scholar] source
- Not checked yetcites [20] Ramsay RR, Gandour RD. Selective modulation of carnitine long-chain acyltransferase activities. Kinetics, inhibitors, and active sites of COT and CPT-II. Adv Exp Med Biol. 1999;466:103–109. [PubMed] [Google Scholar]
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
In the paper
“SREBP in flies regulates fatty acid metabolism (16), which is reminiscent of the function of the Srebp-1 gene in mammals (6).”
What the sources say
- Not checked — no full text of the sourcecites [16] Rawson RB. The SREBP pathway—insights from Insigs and insects. Nat Rev Mol Cell Biol. 2003;4:631–640. doi: 10.1038/nrm1174. [DOI] [PubMed] [Google Scholar] source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
None of the sources cited for this claim have been checked yet.
In the paper
“CPT1a is a mitochondrial enzyme that mediates the transport of long fatty acids across the membrane by binding them to carnitine, and it is the rate-limiting enzyme that regulates fatty acid oxidation (17–20).”
What the sources say
- Not checked — no full text of the sourcecites [17] Brady PS, Ramsay RR, Brady LJ. Regulation of the long-chain carnitine acyltransferases. FASEB J. 1993;7:1039–1044. doi: 10.1096/fasebj.7.11.8370473. [DOI] [PubMed] [Google Scholar] source
- Not checked — no full text of the sourcecites [18] Eaton S, et al. The mitochondrial trifunctional protein: Centre of a beta-oxidation metabolon? Biochem Soc Trans. 2000;28:177–182. doi: 10.1042/bst0280177. [DOI] [PubMed] [Google Scholar] source
- Not checked — no full text of the sourcecites [19] Mannaerts GP, Van Veldhoven PP, Casteels M. Peroxisomal lipid degradation via beta- and alpha-oxidation in mammals. Cell Biochem Biophys. 2000;32:73–87. doi: 10.1385/cbb:32:1-3:73. [DOI] [PubMed] [Google Scholar] source
- Not checked yetcites [20] Ramsay RR, Gandour RD. Selective modulation of carnitine long-chain acyltransferase activities. Kinetics, inhibitors, and active sites of COT and CPT-II. Adv Exp Med Biol. 1999;466:103–109. [PubMed] [Google Scholar]
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“HADHB is the β-subunit of the mitochondrial trifunctional protein, which catalyzes the last three steps of mitochondrial β-oxidation of long-chain fatty acids”
What the sources say
- Not checked — no full text of the sourcecites [17] Brady PS, Ramsay RR, Brady LJ. Regulation of the long-chain carnitine acyltransferases. FASEB J. 1993;7:1039–1044. doi: 10.1096/fasebj.7.11.8370473. [DOI] [PubMed] [Google Scholar] source
- Not checked — no full text of the sourcecites [18] Eaton S, et al. The mitochondrial trifunctional protein: Centre of a beta-oxidation metabolon? Biochem Soc Trans. 2000;28:177–182. doi: 10.1042/bst0280177. [DOI] [PubMed] [Google Scholar] source
- Not checked — no full text of the sourcecites [19] Mannaerts GP, Van Veldhoven PP, Casteels M. Peroxisomal lipid degradation via beta- and alpha-oxidation in mammals. Cell Biochem Biophys. 2000;32:73–87. doi: 10.1385/cbb:32:1-3:73. [DOI] [PubMed] [Google Scholar] source
- Not checked yetcites [20] Ramsay RR, Gandour RD. Selective modulation of carnitine long-chain acyltransferase activities. Kinetics, inhibitors, and active sites of COT and CPT-II. Adv Exp Med Biol. 1999;466:103–109. [PubMed] [Google Scholar]
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“miR-33a and -b have identical seed sequences but differ in 2 of 19 nt of the mature RNA (Fig. S1C).”
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“All quantitative values represent averages from at least 30 cells per well.”
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“Data are the mean ± SEM and are representative of three independent experiments.”
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“suggesting that miR-33a and -b may be an attractive therapeutic target for metabolic syndrome.”
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: fails — It may be too vague to check against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. It may be too vague to check against evidence.
The paper relies on this without support.
IRS2 is an essential component of the insulin-signaling pathway in the liver.
“Moreover, miR-33a and -b also target the insulin receptor substrate 2, an essential component of the insulin-signaling pathway in the liver.”
The paper relies on this without support.
The Srebp1 genes of rats and mice lack miR-33b.
“because the Srebp1 genes of these animal models lack miR-33b.”
The paper relies on this without support.
AKT/PKB phosphorylates FoxO in three conserved sites, leading to FoxO cytoplasmic retention and transcriptional inactivation.
“One of the best documented is the AKT/protein kinase B (PKB) kinase, which phosphorylates FoxO in three conserved sites, leading to FoxO cytoplasmatic retention and transcriptional inactivation.”
The paper relies on this without support.
The Srebp gene of Drosophila controls fatty acid production.
“Interestingly, the Srebp gene of Drosophila controls fatty acid production”
The paper relies on this without support.
Drosophila neither synthesizes sterols nor expresses ABCA1.
“because Drosophila neither synthesizes sterols nor expresses ABCA1.”
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
The source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“It represses insulin receptor substrate 2 (IRS2), protein kinase AMP-activated catalytic subunit a1 (PRKAA1), and sirtuin 6 (SIRT6) 34 , 35) , genes that are important for the maintenance of insulin sensitivity, cellular energy balance, and the mitochondrial function.”
From Critical Role of microRNA-33a/b in Cardiovascular and Metabolic Disease: Molecular Mechanisms and Therapeutic Perspectives (2026) · cites this paper as [34]
Experimental — accuracy not yet measuredThe cited source says what the claim attributes to it.
In the citing paper
“This work led to the demonstration that miR-33a and miR-33b are co-transcribed along with SREBP-2 and SREBP-1, and work in concert with their host genes to help maintain proper lipid levels within the cell (Davalos et al., 2011; Marquart et al., 2010; Najafi-Shoushtari et al., 2010; Rayner et al., 2010).”
From Genetic dissection of the impact of miR-33a and miR-33b during the progression of atherosclerosis (2017) · cites this paper as Davalos et al., 2011
The cited source says what the claim attributes to it.
In the citing paper
“miR-33a and miR-33b help prevent further loss of lipids by targeting genes involved in cholesterol trafficking and efflux”
From Genetic dissection of the impact of miR-33a and miR-33b during the progression of atherosclerosis (2017) · cites this paper as Davalos et al., 2011
The cited source says what the claim attributes to it.
In the citing paper
“MiR-33 suppresses genes involved in mitochondrial β-oxidation, such as carnitine palmitoyltransferase 1A (CPT1A), hydroxyacyl-CoA dehydrogenase trifunctional multienzyme complex subunit b (HADHB), and carnitine O-octanoyltransferase (CROT) 15 , 17 , 34 , 35) .”
From Critical Role of microRNA-33a/b in Cardiovascular and Metabolic Disease: Molecular Mechanisms and Therapeutic Perspectives (2026) · cites this paper as [34]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
Each contradiction between two passages listed here was confirmed by an independent check.
Rated major: it would touch a result — a value a result rests on, reported and recomputed p-values on opposite sides of the significance level, two passages that conflict with no sign which is right, or a cited work retracted before this paper was published.
In the paper
§ Results
“We next evaluated the accumulation of neutral lipids and lipid droplet formation in Huh7 cells incubated with oleate for 24 h and then starved for the next 24 h.”
§ Materials and Methods
“Huh7 cells were transfected with miR-33 or Con-miR as described above and incubated with 1 mM oleate for 12 h. Then, cells were washed two times with cold PBS and starved for the next 24 h.”
Citations
Cites
MicroRNAs: Target Recognition and Regulatory Functions
Bartel, D. P. (2009) · Cell · doi:10.1016/j.cell.2009.01.002 · Cited by 20,068
The functions of animal microRNAs
Ambros, V. (2004) · Nature · doi:10.1038/nature02871 · Cited by 10,728
The metabolic syndrome—a new worldwide definition
Alberti, K. G. M., Zimmet, P., & Shaw, J. (2005) · The Lancet · doi:10.1016/s0140-6736(05)67402-8 · Cited by 9,352
Inflammation and metabolic disorders
Hotamisligil, G. S. (2006) · Nature · doi:10.1038/nature05485 · Cited by 9,199
Alberti, K. G. M. M., Zimmet, P., & Shaw, J. (2006) · Diabetic Medicine · doi:10.1111/j.1464-5491.2006.01858.x · Cited by 6,597
(2008) · doi:10.1038/nrg2290 · Cited by 5,199
Lusis, A. J. (2000) · Nature · doi:10.1038/35025203 · Cited by 4,880
SREBPs: activators of the complete program of cholesterol and fatty acid synthesis in the liver
Horton, J. D., Goldstein, J. L., & Brown, M. S. (2002) · Journal of Clinical Investigation · doi:10.1172/jci15593 · Cited by 4,794
SREBPs: activators of the complete program of cholesterol and fatty acid synthesis in the liver
Horton, J. D., Goldstein, J. L., & Brown, M. S. (2002) · Journal of Clinical Investigation · doi:10.1172/jci0215593 · Cited by 4,092
Silencing of microRNAs in vivo with ‘antagomirs’
Krützfeldt, J., Rajewsky, N., Braich, R., Rajeev, K. G., Tuschl, T., Manoharan, M., & Stoffel, M. (2005) · Nature · doi:10.1038/nature04303 · Cited by 3,949
Cited by
Sorted by citations
MicroRNA therapeutics: towards a new era for the management of cancer and other diseases
Rupaimoole, R., & Slack, F. J. (2017) · Nature Reviews Drug Discovery · doi:10.1038/nrd.2016.246 · Cited by 4,741
MicroRNAs in metabolism and metabolic disorders
Rottiers, V., & Näär, A. M. (2012) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm3313 · Cited by 1,156
“In humans, mir-33a and mir-33b seem to be extensively co-expressed with their host genes in many cells and tissue”
Wang (2012) · doi:10.1161/circresaha.111.261388 · Cited by 957
In vivo delivery of miRNAs for cancer therapy: Challenges and strategies
Chen, Y., Gao, D.-Y., & Huang, L. (2014) · Advanced Drug Delivery Reviews · doi:10.1016/j.addr.2014.05.009 · Cited by 693
Inhibition of miR-33a/b in non-human primates raises plasma HDL and lowers VLDL triglycerides
Rayner, K. J., Esau, C. C., Hussain, F. N., McDaniel, A. L., Marshall, S. M., van Gils, J. M., Ray, T. D., Sheedy, F. J., Goedeke, L., Liu, X., et al. (2011) · Nature · doi:10.1038/nature10486 · Cited by 706
Self-citation
Metadata
- Authors
- Dávalos, A., Goedeke, L., Smibert, P., Ramírez, C. M., Warrier, N. P., Andreo, U., Cirera-Salinas, D., Rayner, K., Suresh, U., Pastor-Pareja, J. C., Esplugues, E., Fisher, E. A., Penalva, L. O. F., Moore, K. J., Suárez, Y., Lai, E. C., & Fernández-Hernando, C.
- Affiliations
- NYU Langone Health (US)
- Department of Developmental Biology, Sloan–Kettering Institute, New York, NY 10065;
- Departments of Medicine and Cell Biology, Leon H. Charney Division of Cardiology and the Marc and Ruti Bell Vascular Biology and Disease Program, New York University School of Medicine, New York, NY 10016;
- The University of Texas at San Antonio Health Science Center (US)
- Yale University (US)
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 2011-05-16
- Volume
- 108
- Issue
- 22
- Pages
- 9232-9237
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC3107310
- OpenAlex
- W2030354790
- Semantic Scholar
- 4a7c3442c0dc1e42524b4ece3797a409b5d0dd26
- Cited by
- 670
- References
- 38
- Citations by year
- 2026: 15 · 2025: 23 · 2024: 24 · 2023: 46 · 2022: 35 · 2021: 48 · 2020: 49 · 2019: 32 · 2018: 45 · 2017: 39 · 2016: 64 · 2015: 56 · 2014: 71 · 2013: 60 · 2012: 52
- FWCI
- 19.00
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (submittedVersion)
- Funders
- American Heart Association
- Deutsche Forschungsgemeinschaft (EXC257)
- National Institutes of Health (5r01ag020255-10, 2r01gm083300-18)
- National Institute on Aging (R01AG20255, R01-AG020255)
- National Heart, Lung, and Blood Institute (R01 HL58541, R01HL16063, P30HL101270, R01HL058541, R01HL107953)
- National Institute of General Medical Sciences (R01-GM083300)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › MicroRNA in disease regulation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Cholesterol and Lipid Metabolism
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Lipid metabolism and disorders
- Keywords
- miR-33a, miR-33b, microRNA, fatty acid oxidation, insulin signaling, insulin receptor substrate 2, SIRT6, AMPK, CPT1A, hydroxyacyl-CoA dehydrogenase, SREBP, cholesterol homeostasis, metabolic syndrome, atherosclerosis, HDL cholesterol, triglycerides, liver, miRNA inhibitors
- MeSH terms
- Animals, Cardiovascular Diseases, Cholesterol, Cytoplasm, Drosophila melanogaster, Fatty Acids, Homeostasis, Humans, Immunohistochemistry, Insulin, Lipids, Phosphorylation, RNA Processing, Post-Transcriptional, Signal Transduction, MicroRNAs
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
A language model drew the claims from the paper on 2026-10-21, under version 3 of the claim definition (model deepseek-v4.1-flash, prompt extract-v3).
A second model labelled each claim on 2026-10-21 (model jev-1.13-20260917, definition revision gold-guideline-v0.2).
Cited sources are checked with a language model’s help (gpt-6-sol).
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
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