CoChat
Sign Up
Cited by 45

The DOI matches its Crossref record; 6 of the 6 references it cites were found in a registry or an index.

CGI-58/ABHD5-Derived Signaling Lipids Regulate Systemic Inflammation and Insulin Action

Lord, Caleb C., Betters, Jenna L., Ivanova, Pavlina T., Milne, Stephen B., Myers, David S., Madenspacher, Jennifer, Thomas, Gwynneth, Chung, Soonkyu, Liu, Mingxia, Davis, Matthew A., Lee, Richard G., Crooke, Rosanne M., Graham, Mark J., Parks, John S., Brasaemle, Dawn L., Fessler, Michael B., Brown, H. Alex, Brown, J. Mark·2012·Diabetes
DOI 10.2337/db11-0994PMC PMC3266405
Open this paper in CoChat — free account

Abstract

Mutations of comparative gene identification 58 (CGI-58) in humans cause Chanarin-Dorfman syndrome, a rare autosomal recessive disease in which excess triacylglycerol (TAG) accumulates in multiple tissues. CGI-58 recently has been ascribed two distinct biochemical activities, including coactivation of adipose triglyceride lipase and acylation of lysophosphatidic acid (LPA). It is noteworthy that both the substrate (LPA) and the product (phosphatidic acid) of the LPA acyltransferase reaction are well-known signaling lipids. Therefore, we hypothesized that CGI-58 is involved in generating lipid mediators that regulate TAG metabolism and insulin sensitivity. Here, we show that CGI-58 is required for the generation of signaling lipids in response to inflammatory stimuli and that lipid second messengers generated by CGI-58 play a critical role in maintaining the balance between inflammation and insulin action. Furthermore, we show that CGI-58 is necessary for maximal TH1 cytokine signaling in the liver. This novel role for CGI-58 in cytokine signaling may explain why diminished CGI-58 expression causes severe hepatic lipid accumulation yet paradoxically improves hepatic insulin action. Collectively, these findings establish that CGI-58 provides a novel source of signaling lipids. These findings contribute insight into the basic mechanisms linking TH1 cytokine signaling to nutrient metabolism.

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/db11-0994

Cites

6 of 6 references verified0 citation errors · 0 not checkable

Statistics

Figures

FIG. 1. CGI-58 KD dissociates hepatic steatosis from insulin resistance. A: Photographs depicting hepatic steatosis and adiposity in C57BL/6N mice fed either a chow or HFD for 10 weeks in conjunction with biweekly injections (25 mg/kg) of either a nontargeting control ASO or ASO targeting KD of CGI-58 (CGI-58 ASO). B–G: Despite hepatic lipid insult, KD of CGI-58 enhances insulin signaling. Mice were fed either a chow or HFD and treated with ASOs for 8 weeks. Mice were fasted for 10 h before saline or insulin injection into the portal vein. Exactly 5 min later, tissues were excised and immediately snap-frozen in liquid nitrogen. Protein extracts from the liver (B), skeletal muscle (C), and adipose tissue (D) were analyzed by Western blotting for total Akt, phospho (p)-Akt (Ser473 and Thr308), and phospho (p)-FoxO1 (Ser256); three representative animals are shown for each group. E–G: Densitometric analyses of insulin signaling: Phospho-Akt protein levels were normalized to total Akt in liver (E), skeletal muscle (F), and adipose tissue (G). □, control ASO; ■, CGI-58 ASO. Data represent the mean ± SEM from three mice per group, and values not sharing a common superscript letter differ significantly (P < 0.05). AU, arbitrary unit. (A high-quality digital representation of this figure is available in the online issue.)
FIG. 1. CGI-58 KD dissociates hepatic steatosis from insulin resistance. A: Photographs depicting hepatic steatosis and adiposity in C57BL/6N mice fed either a chow or HFD for 10 weeks in conjunction with biweekly injections (25 mg/kg) of either a nontargeting control ASO or ASO targeting KD of CGI-58 (CGI-58 ASO). B–G: Despite hepatic lipid insult, KD of CGI-58 enhances insulin signaling. Mice were fed either a chow or HFD and treated with ASOs for 8 weeks. Mice were fasted for 10 h before saline or insulin injection into the portal vein. Exactly 5 min later, tissues were excised and immediately snap-frozen in liquid nitrogen. Protein extracts from the liver (B), skeletal muscle (C), and adipose tissue (D) were analyzed by Western blotting for total Akt, phospho (p)-Akt (Ser473 and Thr308), and phospho (p)-FoxO1 (Ser256); three representative animals are shown for each group. E–G: Densitometric analyses of insulin signaling: Phospho-Akt protein levels were normalized to total Akt in liver (E), skeletal muscle (F), and adipose tissue (G). □, control ASO; ■, CGI-58 ASO. Data represent the mean ± SEM from three mice per group, and values not sharing a common superscript letter differ significantly (P < 0.05). AU, arbitrary unit. (A high-quality digital representation of this figure is available in the online issue.)CC BY-NC-ND · PubMed Central
FIG. 2. CGI-58 KD alters HFD-induced inflammation: Evidence of hepatic cytokine resistance. C57BL/6N mice were fed either a standard chow or HFD in conjunction with biweekly injections of either a nontargeting control ASO (□) or ASO targeting KD of CGI-58 (CGI-58 ASO; ■) for 10 weeks. A: Plasma levels of proinflammatory cytokines, including IL-6 and IL-12p40; monocyte chemoattractant protein-1 (MCP-1); macrophage inflammatory protein-2 (MIP-2); CXCL1 (KC); and regulated upon activation, normal T-cell expressed, and RANTES. Data represent the mean ± SEM from five mice per group, and values not sharing a common superscript letter differ significantly (P < 0.05). ND, levels below limit of detection. B and C: HFD-induced stress kinase activation. Representative immunoblots from liver (B) or epididymal adipose tissue (C) are shown for phospho-IκB kinase α/β (p-IKKα/β; Ser176/180), phospho-mTOR (p-mTOR; Ser2448), and phospho-S6 ribosomal protein (p-S6; Ser235/236). Membranes were probed for β-actin and CGI-58 to serve as loading controls; data from four representative animals are shown for each group.
FIG. 2. CGI-58 KD alters HFD-induced inflammation: Evidence of hepatic cytokine resistance. C57BL/6N mice were fed either a standard chow or HFD in conjunction with biweekly injections of either a nontargeting control ASO (□) or ASO targeting KD of CGI-58 (CGI-58 ASO; ■) for 10 weeks. A: Plasma levels of proinflammatory cytokines, including IL-6 and IL-12p40; monocyte chemoattractant protein-1 (MCP-1); macrophage inflammatory protein-2 (MIP-2); CXCL1 (KC); and regulated upon activation, normal T-cell expressed, and RANTES. Data represent the mean ± SEM from five mice per group, and values not sharing a common superscript letter differ significantly (P < 0.05). ND, levels below limit of detection. B and C: HFD-induced stress kinase activation. Representative immunoblots from liver (B) or epididymal adipose tissue (C) are shown for phospho-IκB kinase α/β (p-IKKα/β; Ser176/180), phospho-mTOR (p-mTOR; Ser2448), and phospho-S6 ribosomal protein (p-S6; Ser235/236). Membranes were probed for β-actin and CGI-58 to serve as loading controls; data from four representative animals are shown for each group.CC BY-NC-ND · PubMed Central
FIG. 3. CGI-58–generated signaling lipids are necessary for maximal TNFα signaling in the liver. A–C: Mice were maintained on a chow diet for 4 weeks in conjunction with biweekly injections (25 mg/kg) of either a nontargeting control ASO (□) or ASO targeting knockdown of CGI-58 (CGI-58 ASO; ■). Mice were fasted for 10 h before injection of saline or TNFα (10 ng) into the portal vein. Exactly 5 min later, the liver was excised and immediately snap-frozen in liquid nitrogen for signaling analyses. A: Hepatic levels of PA and phosphatidylglycerol (PG) were analyzed by mass spectrometry. B: Total hepatic LPAAT activity. Data in A and B represent the mean ± SEM from four mice per group, and values not sharing a common superscript letter differ significantly (P < 0.05). C: Protein extracts from the liver were analyzed for total IκB α (IκBα) and phospho-IκBα (p-IκBα; Ser32); data from four representative animals are shown for each group. D–F: Acute stress kinase activation in primary hepatocytes. Following 4 weeks of ASO treatment, hepatocytes were isolated from control and CGI-58 ASO-treated mice by collagenase perfusion. Freshly isolated hepatocytes were stimulated for 15 min (15’) or 1 h with 100 ng/mL TNFα (D), 10 ng/mL IL-1β (E), or 10 ng/mL IL-6 (F). Downstream signaling was analyzed by immunoblotting for p-JNK (Thr183/Tyr185), phospho-S6 ribosomal protein (p-S6; Ser235/236), and β-actin. Data in D–F represent responses of hepatocytes isolated from three individual mice per condition.
FIG. 3. CGI-58–generated signaling lipids are necessary for maximal TNFα signaling in the liver. A–C: Mice were maintained on a chow diet for 4 weeks in conjunction with biweekly injections (25 mg/kg) of either a nontargeting control ASO (□) or ASO targeting knockdown of CGI-58 (CGI-58 ASO; ■). Mice were fasted for 10 h before injection of saline or TNFα (10 ng) into the portal vein. Exactly 5 min later, the liver was excised and immediately snap-frozen in liquid nitrogen for signaling analyses. A: Hepatic levels of PA and phosphatidylglycerol (PG) were analyzed by mass spectrometry. B: Total hepatic LPAAT activity. Data in A and B represent the mean ± SEM from four mice per group, and values not sharing a common superscript letter differ significantly (P < 0.05). C: Protein extracts from the liver were analyzed for total IκB α (IκBα) and phospho-IκBα (p-IκBα; Ser32); data from four representative animals are shown for each group. D–F: Acute stress kinase activation in primary hepatocytes. Following 4 weeks of ASO treatment, hepatocytes were isolated from control and CGI-58 ASO-treated mice by collagenase perfusion. Freshly isolated hepatocytes were stimulated for 15 min (15’) or 1 h with 100 ng/mL TNFα (D), 10 ng/mL IL-1β (E), or 10 ng/mL IL-6 (F). Downstream signaling was analyzed by immunoblotting for p-JNK (Thr183/Tyr185), phospho-S6 ribosomal protein (p-S6; Ser235/236), and β-actin. Data in D–F represent responses of hepatocytes isolated from three individual mice per condition.CC BY-NC-ND · PubMed Central
FIG. 4. CGI-58 KD alters the systemic inflammatory and metabolic response to endotoxin. C57BL/6N mice were fed a standard chow diet in conjunction with biweekly injections of a nontargeting control ASO (□) or CGI-58 ASO (■) for 4 weeks. Thereafter, mice received a single intraperitoneal injection of either saline or LPS (5 μg/mouse) and were necropsied 6 h after injection. A: Plasma cytokine and acute-phase response protein levels were measured at 1 h (for TNFα only) and 6 h after injection (for IL-6 and IL-12p40 and for SAA and haptoglobin). ND, levels below limit of detection. B and C: qPCR analyses of hepatic (B) and epididymal adipose tissue (C) gene expression. SAP, serum amyloid P-component. WAT, white adipose tissue. D: Hepatic TAG levels. E: Plasma TAG levels at 6 h after injection. Data in A, D, and E represent the mean ± SEM (n = 6), and qPCR data in B and C represent the mean ± SEM (n = 5). Within each panel, values not sharing a common superscript letter differ significantly (P < 0.05). AU, arbitrary unit.
FIG. 4. CGI-58 KD alters the systemic inflammatory and metabolic response to endotoxin. C57BL/6N mice were fed a standard chow diet in conjunction with biweekly injections of a nontargeting control ASO (□) or CGI-58 ASO (■) for 4 weeks. Thereafter, mice received a single intraperitoneal injection of either saline or LPS (5 μg/mouse) and were necropsied 6 h after injection. A: Plasma cytokine and acute-phase response protein levels were measured at 1 h (for TNFα only) and 6 h after injection (for IL-6 and IL-12p40 and for SAA and haptoglobin). ND, levels below limit of detection. B and C: qPCR analyses of hepatic (B) and epididymal adipose tissue (C) gene expression. SAP, serum amyloid P-component. WAT, white adipose tissue. D: Hepatic TAG levels. E: Plasma TAG levels at 6 h after injection. Data in A, D, and E represent the mean ± SEM (n = 6), and qPCR data in B and C represent the mean ± SEM (n = 5). Within each panel, values not sharing a common superscript letter differ significantly (P < 0.05). AU, arbitrary unit.CC BY-NC-ND · PubMed Central
FIG. 5. Proposed model for CGI-58’s integrated role in inflammatory responses and insulin action in the liver. In response to inflammatory stimuli, such as an HFD or LPS, plasma levels of inflammatory cytokines, such TNFα, IL-1β, and IL-6, are increased. These inflammatory cytokines normally signal through their membrane-bound receptors (TNF-R, IL-6-R, and IL-1-R) to promote CGI-58–driven generation of signaling lipids either directly from LPAAT activity or indirectly by coactivating ATGL to generate lipid signals from TAG hydrolysis. CGI-58–generated PA, and likely other signaling lipids, can subsequently act as a critical second messenger to promote the activation of inflammatory stress kinases, such as IKK-β, S6K1, and mTOR. Collectively, these activated stress kinases (IKK-β, S6K1, and mTOR) can facilitate serine phosphorylation (pS) of critical serine residues (Ser307, Ser612, Ser632, and Ser1101) on IRS-1, thereby dampening hepatic insulin signaling. Knocking down CGI-58 diminishes this potent negative regulatory loop, thereby improving hepatic insulin action. IR, insulin receptor. TNF-R, TNF receptor.
FIG. 5. Proposed model for CGI-58’s integrated role in inflammatory responses and insulin action in the liver. In response to inflammatory stimuli, such as an HFD or LPS, plasma levels of inflammatory cytokines, such TNFα, IL-1β, and IL-6, are increased. These inflammatory cytokines normally signal through their membrane-bound receptors (TNF-R, IL-6-R, and IL-1-R) to promote CGI-58–driven generation of signaling lipids either directly from LPAAT activity or indirectly by coactivating ATGL to generate lipid signals from TAG hydrolysis. CGI-58–generated PA, and likely other signaling lipids, can subsequently act as a critical second messenger to promote the activation of inflammatory stress kinases, such as IKK-β, S6K1, and mTOR. Collectively, these activated stress kinases (IKK-β, S6K1, and mTOR) can facilitate serine phosphorylation (pS) of critical serine residues (Ser307, Ser612, Ser632, and Ser1101) on IRS-1, thereby dampening hepatic insulin signaling. Knocking down CGI-58 diminishes this potent negative regulatory loop, thereby improving hepatic insulin action. IR, insulin receptor. TNF-R, TNF receptor.CC BY-NC-ND · PubMed Central

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?

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

Research works printed but not linked: 44

  1. Lass, 2006, Adipose triglyceride lipase-mediated lipolysis of cellular fat stores is activated by CGI-58 and defective in Chanarin-Dorfman Syndrome, Cell Metab, 3, 309, 10.1016/j.cmet.2006.03.005 · DOI
  2. Brown, 2010, CGI-58 knockdown in mice causes hepatic steatosis but prevents diet-induced obesity and glucose intolerance, J Lipid Res, 51, 3306, 10.1194/jlr.M010256 · DOI
  3. Montero-Moran, 2010, CGI-58/ABHD5 is a coenzyme A-dependent lysophosphatidic acid acyltransferase, J Lipid Res, 51, 709, 10.1194/jlr.M001917 · DOI
  4. Ghosh, 2008, CGI-58, the causative gene for Chanarin-Dorfman syndrome, mediates acylation of lysophosphatidic acid, J Biol Chem, 283, 24525, 10.1074/jbc.M801783200 · DOI
  5. Lefèvre, 2001, Mutations in CGI-58, the gene encoding a new protein of the esterase/lipase/thioesterase subfamily, in Chanarin-Dorfman syndrome, Am J Hum Genet, 69, 1002, 10.1086/324121 · DOI
  6. Radner, 2010, Growth retardation, impaired triacylglycerol catabolism, hepatic steatosis, and lethal skin barrier defect in mice lacking comparative gene identification-58 (CGI-58), J Biol Chem, 285, 7300, 10.1074/jbc.M109.081877 · DOI
  7. Wymann, 2008, Lipid signalling in disease, Nat Rev Mol Cell Biol, 9, 162, 10.1038/nrm2335 · DOI
  8. Hla, 2001, Lysophospholipids: receptor revelations, Science, 294, 1875, 10.1126/science.1065323 · DOI
  9. Igal, 1996, Acylglycerol recycling from triacylglycerol to phospholipid, not lipase activity, is defective in neutral lipid storage disease fibroblasts, J Biol Chem, 271, 16644, 10.1074/jbc.271.28.16644 · DOI
  10. Williams, 1991, Neutral lipid storage disease: a possible functional defect in phospholipid-linked triacylglycerol metabolism, Biochim Biophys Acta, 1096, 162, 10.1016/0925-4439(91)90055-E · DOI
  11. Crooke, 2005, An apolipoprotein B antisense oligonucleotide lowers LDL cholesterol in hyperlipidemic mice without causing hepatic steatosis, J Lipid Res, 46, 872, 10.1194/jlr.M400492-JLR200 · DOI
  12. Brown, 2004, Conjugated linoleic acid induces human adipocyte delipidation: autocrine/paracrine regulation of MEK/ERK signaling by adipocytokines, J Biol Chem, 279, 26735, 10.1074/jbc.M401766200 · DOI
  13. Brown, 2008, Inhibition of stearoyl-coenzyme A desaturase 1 dissociates insulin resistance and obesity from atherosclerosis, Circulation, 118, 1467, 10.1161/CIRCULATIONAHA.108.793182 · DOI
  14. Brown, 2008, Targeted depletion of hepatic ACAT2-driven cholesterol esterification reveals a non-biliary route for fecal neutral sterol loss, J Biol Chem, 283, 10522, 10.1074/jbc.M707659200 · DOI
  15. Ivanova, 2007, Glycerophospholipid identification and quantitation by electrospray ionization mass spectrometry, Methods Enzymol, 432, 21, 10.1016/S0076-6879(07)32002-8 · DOI
  16. Chung, 2010, Targeted deletion of hepatocyte ABCA1 leads to very low density lipoprotein triglyceride overproduction and low density lipoprotein hypercatabolism, J Biol Chem, 285, 12197, 10.1074/jbc.M109.096933 · DOI · Paper page
  17. Draper, 2010, ATP-binding cassette transporter G1 deficiency dysregulates host defense in the lung, Am J Respir Crit Care Med, 182, 404, 10.1164/rccm.200910-1580OC · DOI
  18. Lowry, 1951, Protein measurement with the Folin phenol reagent, J Biol Chem, 193, 265, 10.1016/S0021-9258(19)52451-6 · DOI
  19. Callender, 2007, Quantification of diacylglycerol species from cellular extracts by electrospray ionization mass spectrometry using a linear regression algorithm, Anal Chem, 79, 263, 10.1021/ac061083q · DOI
  20. Erion, 2010, Diacylglycerol-mediated insulin resistance, Nat Med, 16, 400, 10.1038/nm0410-400 · DOI
  21. Hotamisligil, 1996, IRS-1-mediated inhibition of insulin receptor tyrosine kinase activity in TNF-alpha- and obesity-induced insulin resistance, Science, 271, 665, 10.1126/science.271.5249.665 · DOI · Paper page
  22. Fingar, 2004, Target of rapamycin (TOR): an integrator of nutrient and growth factor signals and coordinator of cell growth and cell cycle progression, Oncogene, 23, 3151, 10.1038/sj.onc.1207542 · DOI
  23. Hirosumi, 2002, A central role for JNK in obesity and insulin resistance, Nature, 420, 333, 10.1038/nature01137 · DOI · Paper page
  24. Tong, 1999, Involvement of lipid mediators on cytokine signaling and induction of secretory phospholipase A2 in immortalized astrocytes (DITNC), J Mol Neurosci, 12, 89, 10.1007/BF02736923 · DOI
  25. Bursten, 1991, Interleukin-1 rapidly stimulates lysophosphatidate acyltransferase and phosphatidate phosphohydrolase activities in human mesangial cells, J Biol Chem, 266, 20732, 10.1016/S0021-9258(18)54770-0 · DOI
  26. Bursten, 1992, Lipid A activation of glomerular mesangial cells: mimicry of the bioactive lipid, phosphatidic acid, Am J Physiol, 262, C328, 10.1152/ajpcell.1992.262.2.C328 · DOI
  27. Rice, 1994, Protection from endotoxic shock in mice by pharmacologic inhibition of phosphatidic acid, Proc Natl Acad Sci USA, 91, 3857, 10.1073/pnas.91.9.3857 · DOI
  28. Abraham, 1995, Phosphatidic acid signaling mediates lung cytokine expression and lung inflammatory injury after hemorrhage in mice, J Exp Med, 181, 569, 10.1084/jem.181.2.569 · DOI
  29. Hardardóttir, 1994, Effects of endotoxin and cytokines on lipid metabolism, Curr Opin Lipidol, 5, 207, 10.1097/00041433-199405030-00008 · DOI
  30. Shindou, 2009, Recent progress on acyl CoA: lysophospholipid acyltransferase research, J Lipid Res, 50, S46, 10.1194/jlr.R800035-JLR200 · DOI
  31. Nathan, 2002, Points of control in inflammation, Nature, 420, 846, 10.1038/nature01320 · DOI · Paper page
  32. Williams, 1988, Neutral lipid storage disease with ichthyosis: lipid content and metabolism of fibroblasts, J Inherit Metab Dis, 11, 131, 10.1007/BF01799862 · DOI
  33. Hilaire, 1993, Cytoplasmic triacylglycerols and cholesteryl esters are degraded in two separate catabolic pools in cultured human fibroblasts, FEBS Lett, 328, 230, 10.1016/0014-5793(93)80933-L · DOI
  34. Hilaire, 1994, Cellular uptake and catabolism of high-density-lipoprotein triacylglycerols in human cultured fibroblasts: degradation block in neutral lipid storage disease, Biochem J, 297, 467, 10.1042/bj2970467 · DOI
  35. Hilaire, 1995, The turnover of cytoplasmic triacylglycerols in human fibroblasts involves two separate acyl chain length-dependent degradation pathways, J Biol Chem, 270, 27027, 10.1074/jbc.270.45.27027 · DOI
  36. Brown, 2007, CGI-58 facilitates the mobilization of cytoplasmic triglyceride for lipoprotein secretion in hepatoma cells, J Lipid Res, 48, 2295, 10.1194/jlr.M700279-JLR200 · DOI
  37. Subramanian, 2004, Perilipin A mediates the reversible binding of CGI-58 to lipid droplets in 3T3-L1 adipocytes, J Biol Chem, 279, 42062, 10.1074/jbc.M407462200 · DOI
  38. Yamaguchi, 2004, CGI-58 interacts with perilipin and is localized to lipid droplets: possible involvement of CGI-58 mislocalization in Chanarin-Dorfman syndrome, J Biol Chem, 279, 30490, 10.1074/jbc.M403920200 · DOI
  39. Jenkins, 2005, Phospholipase D: a lipid centric review, Cell Mol Life Sci, 62, 2305, 10.1007/s00018-005-5195-z · DOI
  40. Andresen, 2002, The role of phosphatidic acid in the regulation of the Ras/MEK/Erk signaling cascade, FEBS Lett, 531, 65, 10.1016/S0014-5793(02)03483-X · DOI
  41. Exton, 1997, Phospholipase D: enzymology, mechanisms of regulation, and function, Physiol Rev, 77, 303, 10.1152/physrev.1997.77.2.303 · DOI
  42. Topham, 2009, Mammalian diacylglycerol kinases: molecular interactions and biological functions of selected isoforms, 416
  43. Bleich, 1996, Lisofylline, an inhibitor of unsaturated phosphatidic acid generation, ameliorates interleukin-1 beta-induced dysfunction in cultured rat islets, Endocrinology, 137, 4871, 10.1210/endo.137.11.8895359 · DOI
  44. Guidot, 1997, Modulating phosphatidic acid metabolism decreases oxidative injury in rat lungs, Am J Physiol, 273, L957

Cited by

Sorted by citations

See all 45

Metadata

Authors
Lord, C. C., Betters, J. L., Ivanova, P. T., Milne, S. B., Myers, D. S., Madenspacher, J., Thomas, G., Chung, S., Liu, M., Davis, M. A., Lee, R. G., Crooke, R. M., Graham, M. J., Parks, J. S., Brasaemle, D. L., Fessler, M. B., Brown, H. A., & Brown, J. M.
Affiliations
  • Department of Pathology, Section on Lipid Sciences, Wake Forest University School of Medicine, Winston-Salem, North Carolina
  • Department of Pharmacology, Vanderbilt University School of Medicine, Nashville, Tennessee
  • Laboratory of Respiratory Biology, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina
  • Cardiovascular Group, Antisense Drug Discovery, Isis Pharmaceuticals, Carlsbad, California
  • Department of Nutritional Sciences, Rutgers, The State University of New Jersey, New Brunswick, New Jersey
Venue
Diabetes
Publisher
American Diabetes Association
Published
2012-01-17
Volume
61
Issue
2
Pages
355-363
ISSN
  • 0012-1797
  • 1939-327X
DOI
10.2337/db11-0994
PMC
PMC3266405
Cited by
45
References
6
Language
en
Licence
creativecommons.org/licenses/by-nc-nd/3.0/ (vor, 3510 d)

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