CGI-58 knockdown sequesters diacylglycerols in lipid droplets/ER-preventing diacylglycerol-mediated hepatic insulin resistance

Proceedings of the National Academy of Sciences of the United States of America

Volumn 110, Issue 5, 2013, Pages 1869-1874

  Cantley, Jennifer L ^a,b   Yoshimura, Toru ^b   Camporez, Joao Paulo G ^b   Zhang, Dongyan ^a,b   Jornayvaz, Francois R ^b   Kumashiro, Naoki ^a,b   Guebre Egziabher, Fitsum ^b   Jurczak, Michael J ^b   Kahn, Mario ^a,b   Guigni, Blas A ^a,b   Serr, Julie ^b   Hankin, Joseph ^c   Murphy, Robert C ^c   Cline, Gary W ^a,b   Bhanot, Sanjay ^d   Manchem, Vara Prasad ^d   Brown, J Mark ^e   Samuel, Varman T ^b   Shulman, Gerald I ^a,b  

^a HOWARD HUGHES MEDICAL INSTITUTE   (United States)

^b YALE UNIVERSITY SCHOOL OF MEDICINE   (United States)

^c UNIVERSITY OF COLORADO SCHOOL OF MEDICINE   (United States)

^d ISIS PHARMACEUTICALS   (United States)

^e WAKE FOREST SCHOOL OF MEDICINE   (United States)

Author keywords

Nonalcoholic fatty liver disease; Type 2 diabetes

Indexed keywords

ANTISENSE OLIGONUCLEOTIDE; CERAMIDE; COMPARATIVE GENE IDENTIFICATION 58 PROTEIN; DIACYLGLYCEROL; FAT DROPLET; INSULIN; LIPOPROTEIN; MEMBRANE LIPID; PROTEIN KINASE C EPSILON; TRIACYLGLYCEROL; UNCLASSIFIED DRUG;

ADIPOCYTE; ADIPOSE TISSUE; ANIMAL CELL; ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; ARTICLE; BIOSYNTHESIS; CELL COMPARTMENTALIZATION; CELL FUNCTION; CONTROLLED STUDY; ENDOPLASMIC RETICULUM; GENE EXPRESSION; HYPERINSULINEMIA; INSULIN RESISTANCE; INSULIN SENSITIVITY; LIPID DIET; LIPID LIVER LEVEL; LIPID STORAGE; LIPOTOXICITY; LIVER PROTECTION; MOUSE; NONHUMAN; PRIORITY JOURNAL; SIGNAL TRANSDUCTION; WEIGHT GAIN;

1-ACYLGLYCEROL-3-PHOSPHATE O-ACYLTRANSFERASE; ADIPOSE TISSUE, WHITE; ANIMALS; CELL MEMBRANE; DIET, HIGH-FAT; DIGLYCERIDES; ENDOPLASMIC RETICULUM; GENE EXPRESSION; GENE KNOCKDOWN TECHNIQUES; HUMANS; IMMUNOBLOTTING; INJECTIONS, INTRAPERITONEAL; INSULIN RESISTANCE; LIPIDS; LIVER; MALE; MICE; MICE, INBRED C57BL; OLIGONUCLEOTIDES, ANTISENSE; PROTEIN KINASE C-EPSILON; PROTEIN TRANSPORT; REVERSE TRANSCRIPTASE POLYMERASE CHAIN REACTION;

EID: 84873178604     PISSN: 00278424     EISSN: 10916490     Source Type: Journal    
DOI: 10.1073/pnas.1219456110     Document Type: Article

References (35)

1. Cheung O, Sanyal AJ (2010) Recent advances in nonalcoholic fatty liver disease. Curr Opin Gastroenterol 26(3):202-208.
2. Samuel VT, Shulman GI (2012) Mechanisms for insulin resistance: Common threads and missing links. Cell 148(5):852-871.
3. Neschen S, et al. (2007) n-3 Fatty acids preserve insulin sensitivity in vivo in a peroxisome proliferator-activated receptor-alpha-dependent manner. Diabetes 56(4):1034-1041. (Pubitemid 46525082)
4. Shulman GI (2000) Cellular mechanisms of insulin resistance. J Clin Invest 106(2):171-176. (Pubitemid 30483118)
5. Bikman BT, Summers SA (2011) Ceramides as modulators of cellular and whole-body metabolism. J Clin Invest 121(11):4222-4230.
6. Jornayvaz FR, Shulman GI (2012) Diacylglycerol activation of protein kinase Ce and hepatic insulin resistance. Cell Metab 15(5):574-584.
7. Samuel VT, Petersen KF, Shulman GI (2010) Lipid-induced insulin resistance: Unravelling the mechanism. Lancet 375(9733):2267-2277.
8. Samuel VT, et al. (2004) Mechanism of hepatic insulin resistance in non-alcoholic fatty liver disease. J Biol Chem 279(31):32345-32353. (Pubitemid 39014687)
9. Samuel VT, et al. (2007) Inhibition of protein kinase Cepsilon prevents hepatic insulin resistance in nonalcoholic fatty liver disease. J Clin Invest 117(3):739-745. (Pubitemid 46348532)
10. Griffin ME, et al. (1999) Free fatty acid-induced insulin resistance is associated with activation of protein kinase C theta and alterations in the insulin signaling cascade. Diabetes 48(6):1270-1274. (Pubitemid 29241025)
11. Li Y, et al. (2004) Protein kinase C Theta inhibits insulin signaling by phosphorylating IRS1 at Ser (1101). J Biol Chem 279(44):45304-45307. (Pubitemid 39491511)
12. Yu C, et al. (2002) Mechanism by which fatty acids inhibit insulin activation of insulin receptor substrate-1(IRS-1)-associated phosphatidylinositol 3-kinase activity in muscle. J Biol Chem 277 (52):50230-50236. (Pubitemid 36042170)
13. Chavez JA, Summers SA (2012) A ceramide-centric view of insulin resistance. Cell Metab 15(5):585-594.
14. Holland WL, et al. (2007) Inhibition of ceramide synthesis ameliorates glucocorticoid-, saturated-fat-, and obesity-induced insulin resistance. Cell Metab 5(3):167-179.
15. Schmitz-Peiffer C (2010) Targeting ceramide synthesis to reverse insulin resistance. Diabetes 59(10):2351-2353.
16. Kumashiro N, et al. (2011) Cellular mechanism of insulin resistance in nonalcoholic fatty liver disease. Proc Natl Acad Sci USA 108(39):16381-16385.
17. Bergman BC, Hunerdosse DM, Kerege A, Playdon MC, Perreault L (2012) Localisation and composition of skeletal muscle diacylglycerol predicts insulin resistance in humans. Diabetologia 55(4):1140-1150.
18. Anstee QM, Goldin RD (2006) Mouse models in non-alcoholic fatty liver disease and steatohepatitis research. Int J Exp Pathol 87(1):1-16.
19. Benhamed F, et al. (2012) The lipogenic transcription factor ChREBP dissociates hepatic steatosis from insulin resistance in mice and humans. J Clin Invest 122(6):2176-2194.
20. Brown JM, et al. (2010) CGI-58 knockdown in mice causes hepatic steatosis but prevents diet-induced obesity and glucose intolerance. J Lipid Res 51(11):3306-3315.
21. Sun Z, et al. (2012) Hepatic Hdac3 promotes gluconeogenesis by repressing lipid synthesis and sequestration. Nat Med 18(6):934-942.
22. Lass A, et al. (2006) Adipose triglyceride lipase-mediated lipolysis of cellular fat stores is activated by CGI-58 and defective in Chanarin-Dorfman Syndrome. Cell Metab 3(5):309-319.
23. Lu X, Yang X, Liu J (2010) Differential control of ATGL-mediated lipid droplet degradation by CGI-58 and G0S2. Cell Cycle 9(14):2719-2725.
24. Haemmerle G, et al. (2006) Defective lipolysis and altered energy metabolism in mice lacking adipose triglyceride lipase. Science 312(5774):734-737.
25. Wang S, et al. (2008) Lipolysis and the integrated physiology of lipid energy metabolism. Mol Genet Metab 95(3):117-126.
26. Guilherme A, Virbasius JV, Puri V, Czech MP (2008) Adipocyte dysfunctions linking obesity to insulin resistance and type 2 diabetes. Nat Rev Mol Cell Biol 9(5):367-377. (Pubitemid 351574198)
27. Christianson JL, Boutet E, Puri V, Chawla A, Czech MP (2010) Identification of the lipid droplet targeting domain of the Cidea protein. J Lipid Res 51(12):3455-3462.
28. Lord CC, et al. (2012) CGI-58/ABHD5-derived signaling lipids regulate systemic inflammation and insulin action. Diabetes 61(2):355-363.
29. Rabe K, Lehrke M, Parhofer KG, Broedl UC (2008) Adipokines and insulin resistance. Mol Med 14(11-12):741-751.
30. Rasouli N, Kern PA (2008) Adipocytokines and the metabolic complications of obesity. J Clin Endocrinol Metab 93(11):Suppl 1): S64-S73.
31. Martin S, Parton RG (2006) Lipid droplets: A unified view of a dynamic organelle. Nat Rev Mol Cell Biol 7(5):373-378.
32. Wolins NE, Brasaemle DL, Bickel PE (2006) A proposed model of fat packaging by exchangeable lipid droplet proteins. FEBS Lett 580(23):5484-5491. (Pubitemid 44465908)
33. Kienesberger PC, et al. (2009) Adipose triglyceride lipase deficiency causes tissuespecific changes in insulin signaling. J Biol Chem 284(44):30218-30229.
34. Radner FP, et al. (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 (10):7300-7311.
35. Eichmann TO, et al. (2012) Studies on the substrate and stereo/regioselectivity of adipose triglyceride lipase, hormone-sensitive lipase, and diacylglycerol-O-acyltransferases. J Biol Chem 287(49):41446-41457.