CoChat
Sign Up
Cited by 12

The DOI matches its Crossref record; 2 of the 2 references it cites were found in a registry or an index.

A Novel Function of Hepatic FOG2 in Insulin Sensitivity and Lipid Metabolism Through PPARα

Guo, Yajie, Yu, Junjie, Deng, Jiali, Liu, Bin, Xiao, Yuzhong, Li, Kai, Xiao, Fei, Yuan, Feixiang, Liu, Yong, Chen, Shanghai, Guo, Feifan·2016·Diabetes
DOI 10.2337/db15-1565
Open this paper in CoChat — free account

Abstract

Friend of GATA 2 (FOG2) is a transcriptional cofactor involved mostly in cardiac function. The aim of this study was to investigate the role of hepatic FOG2 in insulin sensitivity and lipid accumulation. FOG2 overexpression by adenovirus-expressing FOG2 (Ad-FOG2) significantly attenuates insulin signaling in hepatocytes in vitro. Opposite effects were observed when FOG2 was knocked down through adenovirus-expressing small hairpin RNA for FOG2 (Ad-shFOG2). Furthermore, FOG2 knockdown by Ad-shFOG2 ameliorated insulin resistance in leptin receptor–mutated (db/db) mice, and FOG2 overexpression by Ad-FOG2 attenuated insulin sensitivity in C57BL/6J wild-type (WT) mice. In addition, Ad-FOG2 reduced, whereas Ad-shFOG2 promoted, hepatic triglyceride (TG) accumulation in WT mice under fed or fasted conditions, which was associated with increased or decreased hepatic peroxisome proliferator–activated receptor α (PPARα) expression, respectively. Moreover, the improved insulin sensitivity and increased hepatic TG accumulation by Ad-shFOG2 were largely reversed by adenovirus-expressing PPARα (Ad-PPARα) in WT mice. Finally, we generated FOG2 liver-specific knockout mice and found that they exhibit enhanced insulin sensitivity and elevated hepatic TG accumulation, which were also reversed by Ad-PPARα. Taken together, the results demonstrate a novel function of hepatic FOG2 in insulin sensitivity and lipid metabolism through PPARα.

Overview

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Integrity signals

Registry

Crossref · 10.2337/db15-1565

Cites

2 of 2 references verified0 citation errors · 0 not checkable

Statistics

Verification

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

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?

  • RNAscope smFISH validated increased expression of GRAMD1B, VEGFB, and NR2F2 in mutant MAPT R406W HNOs compared to isogenic controls.

    “RNAscope smFISH validated the increased expression of GRAMD1B, VEGFB, and NR2F2 in mutant MAPT R406W HNOs compared to isogenic controls.”

    From GRAMD1B is a regulator of lipid homeostasis, autophagic flux and phosphorylated tau (2025) · cites this paper as [71]

  • Using scRNA-seq, genes (e.g., GRAMD1B, VEGFB, MIAT, COMT, NRP1, DSEL, NR2F2, HMGCS1, and LDLR) and biological pathways related to lipid metabolism are increased in excitatory neurons of MAPT R406W mutant HNOs compared to isogenic control HNOs.

    “Using scRNA-seq, we found that genes (e.g., GRAMD1B, VEGFB, MIAT, COMT, NRP1, DSEL, NR2F2, HMGCS1, and LDLR)9,58,66,69–71 and biological pathways related to lipid metabolism are increased in excitatory neurons of MAPT R406W mutant HNOs compared to isogenic control HNOs (Fig. 4a, b and Supplementary Fig. 2a–c).”

    From GRAMD1B is a regulator of lipid homeostasis, autophagic flux and phosphorylated tau (2025) · cites this paper as [71]

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

Citations

Cites

Flagged first, then by citations

Research works printed but not linked: 41

  1. Birkenfeld, 2014, Nonalcoholic fatty liver disease, hepatic insulin resistance, and type 2 diabetes, Hepatology, 59, 713, 10.1002/hep.26672 · DOI
  2. Kumashiro, 2011, Cellular mechanism of insulin resistance in nonalcoholic fatty liver disease, Proc Natl Acad Sci U S A, 108, 16381, 10.1073/pnas.1113359108 · DOI · Paper page
  3. Savage, 2007, Disordered lipid metabolism and the pathogenesis of insulin resistance, Physiol Rev, 87, 507, 10.1152/physrev.00024.2006 · DOI · Paper page
  4. Matsumoto, 2006, Dual role of transcription factor FoxO1 in controlling hepatic insulin sensitivity and lipid metabolism, J Clin Invest, 116, 2464
  5. Liu, 2014, Hepatic miR-378 targets p110α and controls glucose and lipid homeostasis by modulating hepatic insulin signalling, Nat Commun, 5, 5684, 10.1038/ncomms6684 · DOI
  6. Matsusue, 2003, Liver-specific disruption of PPARgamma in leptin-deficient mice improves fatty liver but aggravates diabetic phenotypes, J Clin Invest, 111, 737, 10.1172/JCI200317223 · DOI · Paper page
  7. Tevosian, 1999, FOG-2: A novel GATA-family cofactor related to multitype zinc-finger proteins friend of GATA-1 and U-shaped, Proc Natl Acad Sci U S A, 96, 950, 10.1073/pnas.96.3.950 · DOI
  8. Svensson, 1999, Molecular cloning of FOG-2: a modulator of transcription factor GATA-4 in cardiomyocytes, Proc Natl Acad Sci U S A, 96, 956, 10.1073/pnas.96.3.956 · DOI
  9. Lu, 1999, FOG-2, a heart- and brain-enriched cofactor for GATA transcription factors, Mol Cell Biol, 19, 4495, 10.1128/MCB.19.6.4495 · DOI
  10. Zhou, 2009, Fog2 is critical for cardiac function and maintenance of coronary vasculature in the adult mouse heart, J Clin Invest, 119, 1462, 10.1172/JCI38723 · DOI
  11. Tevosian, 2000, FOG-2, a cofactor for GATA transcription factors, is essential for heart morphogenesis and development of coronary vessels from epicardium, Cell, 101, 729, 10.1016/S0092-8674(00)80885-5 · DOI
  12. Manuylov, 2007, Fog2 excision in mice leads to premature mammary gland involution and reduced Esr1 gene expression, Oncogene, 26, 5204, 10.1038/sj.onc.1210333 · DOI
  13. Hyun, 2009, Conserved MicroRNA miR-8/miR-200 and its target USH/FOG2 control growth by regulating PI3K, Cell, 139, 1096, 10.1016/j.cell.2009.11.020 · DOI
  14. Dou, 2013, miR-200s contribute to interleukin-6 (IL-6)-induced insulin resistance in hepatocytes, J Biol Chem, 288, 22596, 10.1074/jbc.M112.423145 · DOI
  15. Jack, 2010, GATA proteins work together with friend of GATA (FOG) and C-terminal binding protein (CTBP) co-regulators to control adipogenesis, J Biol Chem, 285, 32405, 10.1074/jbc.M110.141317 · DOI
  16. Settembre, 2014, Lysosome: regulator of lipid degradation pathways, Trends Cell Biol, 24, 743, 10.1016/j.tcb.2014.06.006 · DOI
  17. Yu, 2015, Hepatic phosphoserine aminotransferase 1 regulates insulin sensitivity in mice via tribbles homolog 3, Diabetes, 64, 1591, 10.2337/db14-1368 · DOI
  18. Xiao, 2014, A novel function of microRNA 130a-3p in hepatic insulin sensitivity and liver steatosis, Diabetes, 63, 2631, 10.2337/db13-1689 · DOI
  19. Taniguchi, 2006, Critical nodes in signalling pathways: insights into insulin action, Nat Rev Mol Cell Biol, 7, 85, 10.1038/nrm1837 · DOI · Paper page
  20. Rui, 2014, Energy metabolism in the liver, Compr Physiol, 4, 177, 10.1002/cphy.c130024 · DOI
  21. Guo, 2007, The GCN2 eIF2alpha kinase regulates fatty-acid homeostasis in the liver during deprivation of an essential amino acid, Cell Metab, 5, 103, 10.1016/j.cmet.2007.01.001 · DOI
  22. Clemenz, 2008, Liver-specific peroxisome proliferator-activated receptor alpha target gene regulation by the angiotensin type 1 receptor blocker telmisartan, Diabetes, 57, 1405, 10.2337/db07-0839 · DOI
  23. Xiao, 2016, Activation of ERK1/2 ameliorates liver steatosis in leptin receptor-deficient (db/db) mice via stimulating ATG7-dependent autophagy, Diabetes, 65, 393, 10.2337/db15-1024 · DOI
  24. Kersten, 1999, Peroxisome proliferator-activated receptor alpha mediates the adaptive response to fasting, J Clin Invest, 103, 1489, 10.1172/JCI6223 · DOI · Paper page
  25. Fang, 2012, Identification of a binding motif specific to HNF4 by comparative analysis of multiple nuclear receptors, Nucleic Acids Res, 40, 5343, 10.1093/nar/gks190 · DOI
  26. Huggins, 2001, Friend of GATA 2 physically interacts with chicken ovalbumin upstream promoter-TF2 (COUP-TF2) and COUP-TF3 and represses COUP-TF2-dependent activation of the atrial natriuretic factor promoter, J Biol Chem, 276, 28029, 10.1074/jbc.M103577200 · DOI
  27. Shibata, 2003, Regulation of differential COUP-TF-coregulator interactions in adrenal cortical steroidogenesis, J Steroid Biochem Mol Biol, 85, 449, 10.1016/S0960-0760(03)00217-6 · DOI
  28. Leone, 1999, A critical role for the peroxisome proliferator-activated receptor alpha (PPARalpha) in the cellular fasting response: the PPARalpha-null mouse as a model of fatty acid oxidation disorders, Proc Natl Acad Sci U S A, 96, 7473, 10.1073/pnas.96.13.7473 · DOI · Paper page
  29. Du, 2003, TRB3: a tribbles homolog that inhibits Akt/PKB activation by insulin in liver, Science, 300, 1574, 10.1126/science.1079817 · DOI · Paper page
  30. Aasum, 2002, Cardiac function and metabolism in type 2 diabetic mice after treatment with BM 17.0744, a novel PPAR-alpha activator, Am J Physiol Heart Circ Physiol, 283, H949, 10.1152/ajpheart.00226.2001 · DOI · Paper page
  31. Chou, 2002, WY14,643, a peroxisome proliferator-activated receptor alpha (PPARalpha ) agonist, improves hepatic and muscle steatosis and reverses insulin resistance in lipoatrophic A-ZIP/F-1 mice, J Biol Chem, 277, 24484, 10.1074/jbc.M202449200 · DOI
  32. Koh, 2003, Peroxisome proliferator-activated receptor (PPAR)-alpha activation prevents diabetes in OLETF rats: comparison with PPAR-gamma activation, Diabetes, 52, 2331, 10.2337/diabetes.52.9.2331 · DOI
  33. Panz, 1997, Improved glucose tolerance after effective lipid-lowering therapy with bezafibrate in a patient with lipoatrophic diabetes mellitus: a putative role for Randle’s cycle in its pathogenesis, Clin Endocrinol (Oxf), 46, 365, 10.1046/j.1365-2265.1997.970912.x · DOI
  34. Ye, 2001, Peroxisome proliferator-activated receptor (PPAR)-alpha activation lowers muscle lipids and improves insulin sensitivity in high fat-fed rats: comparison with PPAR-gamma activation, Diabetes, 50, 411, 10.2337/diabetes.50.2.411 · DOI
  35. Bernal-Mizrachi, 2007, An afferent vagal nerve pathway links hepatic PPARalpha activation to glucocorticoid-induced insulin resistance and hypertension, Cell Metab, 5, 91, 10.1016/j.cmet.2006.12.010 · DOI
  36. Tordjman, 2001, PPARalpha deficiency reduces insulin resistance and atherosclerosis in apoE-null mice, J Clin Invest, 107, 1025, 10.1172/JCI11497 · DOI
  37. Bernal-Mizrachi, 2003, Dexamethasone induction of hypertension and diabetes is PPAR-alpha dependent in LDL receptor-null mice, Nat Med, 9, 1069, 10.1038/nm898 · DOI
  38. Pineda Torra, 2002, Characterization of the human PPARalpha promoter: identification of a functional nuclear receptor response element, Mol Endocrinol, 16, 1013
  39. Li, 2009, The nuclear orphan receptor COUP-TFII plays an essential role in adipogenesis, glucose homeostasis, and energy metabolism, Cell Metab, 9, 77, 10.1016/j.cmet.2008.12.002 · DOI · Paper page
  40. Pereira, 1999, The orphan nuclear receptor COUP-TFII is required for angiogenesis and heart development, Genes Dev, 13, 1037, 10.1101/gad.13.8.1037 · DOI
  41. Park, 2013, FOG2 protein down-regulation by transforming growth factor-β1-induced microRNA-200b/c leads to Akt kinase activation and glomerular mesangial hypertrophy related to diabetic nephropathy, J Biol Chem, 288, 22469, 10.1074/jbc.M113.453043 · DOI

Cited by

Sorted by citations

Metadata

Authors
Guo, Y., Yu, J., Deng, J., Liu, B., Xiao, Y., Li, K., Xiao, F., Yuan, F., Liu, Y., Chen, S., & Guo, F.
Affiliations
Key Laboratory of Nutrition and Metabolism, Institute for Nutritional Sciences, Shanghai Institute for Biological Sciences, Chinese Academy of Sciences, Graduate School of the Chinese Academy of Sciences, Shanghai, China
Venue
Diabetes
Publisher
American Diabetes Association
Published
2016-05-03
Volume
65
Issue
8
Pages
2151-2163
ISSN
  • 0012-1797
  • 1939-327X
DOI
10.2337/db15-1565
Cited by
12
References
2
Language
en
Licence
www.diabetesjournals.org/site/license (vor, 274 d)
Funders
National Natural Science Foundation of China (81130076, 81325005, 31271269, 81390350, 81300659)

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.

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.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review