DGAT1-dependent triacylglycerol storage by macrophages protects mice from diet-induced insulin resistance and inflammation

Journal of Clinical Investigation

Volumn 120, Issue 3, 2010, Pages 756-767

  Koliwad, Suneil K ^a,b   Streeper, Ryan S ^a   Monetti, Mara ^a   Cornelissen, Ivo ^b   Chan, Liana ^a   Terayama, Koji ^c   Naylor, Stephen ^b   Rao, Meghana ^a   Hubbard, Brian ^d   Farese Jr , Robert V ^a,b  

^a GLADSTONE INSTITUTE OF CARDIOVASCULAR DISEASE   (United States)

^b UNIVERSITY OF CALIFORNIA   (United States)

^c DAIICHI SANKYO CO   (Japan)

^d MERCK RESEARCH LABORATORIES   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

DIACYLGLYCEROL ACYLTRANSFERASE 1; MESSENGER RNA; PEROXISOME PROLIFERATOR ACTIVATED RECEPTOR GAMMA AGONIST; SATURATED FATTY ACID; TRIACYLGLYCEROL;

ADIPOCYTE; ANIMAL CELL; ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; ARTICLE; BONE MARROW TRANSPLANTATION; CELL ISOLATION; CELL METABOLISM; CELL PROTECTION; CONTROLLED STUDY; DIET INDUCED OBESITY; INFLAMMATION; INSULIN RESISTANCE; LIPID STORAGE; MACROPHAGE ACTIVATION; MOUSE; NONHUMAN; OBESITY; PHENOTYPE; PRIORITY JOURNAL; PROTEIN EXPRESSION; WHITE ADIPOSE TISSUE; WILD TYPE;

ADIPOCYTES; ADIPOSE TISSUE, WHITE; ANIMALS; DIACYLGLYCEROL O-ACYLTRANSFERASE; DIET; FATTY ACIDS; GENE EXPRESSION REGULATION, ENZYMOLOGIC; INFLAMMATION; INSULIN RESISTANCE; MACROPHAGES; MICE; MICE, KNOCKOUT; OBESITY; PPAR GAMMA; TRIGLYCERIDES;

EID: 77949690002     PISSN: 00219738     EISSN: 15588238     Source Type: Journal    
DOI: 10.1172/JCI36066     Document Type: Article

References (60)

1. Lumeng CN, Bodzin JL, Saltiel AR. Obesity induces a phenotypic switch in adipose tissue macrophage polarization. J Clin Invest. 2007;117(1):175-184.
2. Xu H, et al. Chronic inflammation in fat plays a crucial role in the development of obesity-related insulin resistance. J Clin Invest. 2003;112(12):1821-1830.
3. Wellen K, Hotamisligil G. Obesity-induced inflammatory changes in adipose tissue. J Clin Invest. 2003;112(12):1785-1788.
4. Cinti S, et al. Adipocyte death defines macrophage localization and function in adipose tissue of obese mice and humans. J Lipid Res. 2005;46(11):2347-2355.
5. Weisberg SP, et al. Obesity is associated with macrophage accumulation in adipose tissue. J Clin Invest. 2003;112(12):1796-1808.
6. Hotamisligil GS. Inflammation and metabolic disorders. Nature. 2006;444(7121):860-867.
7. Sartipy P, Loskutoff D. Monocyte chemoattractant protein 1 in obesity and insulin resistance. Proc Natl Acad Sci U S A. 2003;100(12):7265-7270.
8. Shoelson S, Lee J, Goldfine A. Inflammation and insulin resistance. J Clin Invest. 2006;116(7):1793-1801.
9. Linton M, Fazio S. Macrophages, inflammation, and atherosclerosis. Int J Obes Relat Metab Disord. 2003;27(Suppl 3):S35-S40.
10. Boden G. Interaction between free fatty acids and glucose metabolism. Curr Opin Clin Nutr Metab Care. 2002;5(5):545-549.
11. Kim J. Fat uses a TOLL-road to connect inflammation and diabetes. Cell Metab. 2006;4(6):417-419.
12. Laine PS, et al. Palmitic acid induces IP-10 expression in human macrophages via NF-kappaB activation. Biochem Biophys Res Commun. 2007;358(1):150-155.
13. Nguyen MT, et al. A subpopulation of macrophages infiltrates hypertrophic adipose tissue and is activated by free fatty acids via toll-like receptors 2 and 4 and JNK-dependent pathways. J Biol Chem. 2007;282(48):35279-35292.
14. Suganami T, et al. Role of the Toll-like receptor 4/NF-kappaB pathway in saturated fatty acid-induced inflammatory changes in the interaction between adipocytes and macrophages. Arterioscler Thromb Vasc Biol. 2007;27(1):84-91.
15. Shi H, Mokoeva MV, Inouye K, Tzameie I, Yin H, Flier JS. TLR4 links innate immunity and fatty acid-induced insulin resistance. J Clin Invest. 2006;116(11):3015-3025.
16. Hirosumi J, et al. A central role for JNK in obesity and insulin resistance. Nature. 2002;420(6913):333-336.
17. Lee JY, et al. Saturated fatty acid activates but poly-unsaturated fatty acid inhibits Toll-like receptor 2 dimerized with Toll-like receptor 6 or 1. J Biol Chem. 2004;279(17):16971-16979.
18. Xu H, et al. Molecular recognition of fatty acids by peroxisome proliferator-activated receptors. Mol Cell. 1999;3(3):397-403.
19. Ricote M, Li AC, Willson TM, Kelly CJ, Glass CK. The peroxisome proliferator-activated receptor-γ is a negative regulator of macrophage activation. Nature. 1998;391(6662):79-82.
20. Martins de Lima T, et al. Mechanisms by which fatty acids regulate leucocyte function. Clin Sci. 2007;113(2):65-77.
21. Fueller M, Wang D, Tigyi G, Siess W. Activation of human monocytic cells by lysophosphatidic acid and sphingosine-1-phosphate. Cell Signal. 2003;15(4):367-375.
22. Hammarstrom S, et al. Novel eicosanoid activators of PPAR gamma formed by RAW 264.7 macrophage cultures. Adv Exp Med Biol. 2002;507:343-349.
23. Yen CL, Stone SJ, Koliwad S, Harris C, Farese RV Jr. Thematic review series: glycerolipids. DGAT enzymes and triacylglycerol biosynthesis. J Lipid Res. 2008;49(11):2283-2301.
24. Chen HC, Stone SJ, Zhou P, Buhman KK, Farese RV Jr. Dissociation of obesity and impaired glucose disposal in mice overexpressing acyl coenzyme a: diacylglycerol acyltransferase 1 in white adipose tissue. Diabetes. 2002;51(11):3189-3195.
25. Levin MC, et al. Increased lipid accumulation and insulin resistance in transgenic mice expressing DGAT2 in glycolytic (type II) muscle. Am J Physiol Endocrinol Metab. 2007;293(6):E1772-E1781.
26. Monetti M, et al. Dissociation of hepatic steatosis and insulin resistance in mice overexpressing DGAT in the liver. Cell Metab. 2007;6(1):69-78.
27. Listenberger LL, et al. Triglyceride accumulation protects against fatty acid-induced lipotoxicity. Proc Natl Acad Sci U S A. 2003;100(6):3077- 3082.
28. Ruan H, Pownall H, Lodish H. Troglitazone antagonizes tumor necrosis factor-alpha-induced reprogramming of adipocyte gene expression by inhibiting the transcriptional regulatory functions of NF-kappaB. J Biol Chem. 2003;278(30):28181-28192.
29. Kim JY, et al. Obesity-associated improvements in metabolic profile through expansion of adipose tissue. J Clin Invest. 2007;117(9):2621- 2637.
30. Ranganathan G, et al. The lipogenic enzymes DGAT1, FAS, and LPL in adipose tissue: effects of obesity, insulin resistance, and TZD treatment. J Lipid Res. 2006;47(11):2444-2450.
31. Hevener A, et al. Macrophage PPAR gamma is required for normal skeletal muscle and hepatic insulin sensitivity and full antidiabetic effects of thiazolidinediones. J Clin Invest. 2007;117(6):1658-1669.
32. Odegaard JI, et al. Macrophage-specific PPARgamma controls alternative activation and improves insulin resistance. Nature. 2007;447(7148):1116- 1120.
33. Mohanty P, et al. Evidence for a potent anti-inflammatory effect of rosiglitazone. J Clin Endocrinol Metab. 2004;89(6):2728-2735.
34. Makowski L, et al. Lack of macrophage fatty-acid-binding protein aP2 protects mice deficient in apolipoprotein E against atherosclerosis. Nat Med. 2001;7(6):699-705.
35. Rolph MS, et al. Regulation of dendritic cell function and T cell priming by the fatty acid-binding protein aP2. J Immunol. 2006;177(11):7794- 7801.
36. Steppan CM, et al. The hormone resistin links obesity to diabetes. Nature. 2001;409(6818):307-312.
37. Pajvani U, et al. Complex distribution, not absolute amount of adiponectin, correlates with thiazolidinedione-mediated improvement in insulin sensitivity. J Biol Chem. 2004;279(13):12152-12162.
38. Maeda N, et al. Diet-induced insulin resistance in mice lacking adiponectin/ACRP30. Nat Med. 2002;8(7):731-737.
39. Streeper RS, Koliwad SK, Villanueva CJ, Farese RV Jr. Effects of DGAT1 deficiency on energy and glucose metabolism are independent of adiponectin. Am J Physiol Endocrinol Metab. 2006; 291(2):E388-E394.
40. Yamauchi T, et al. The fat-derived hormone adiponectin reverses insulin resistance associated with both lipoatrophy and obesity. Nat Med. 2001;7(8):941-946.
41. Okamoto Y, et al. Adiponectin inhibits the production of CXC receptor 3 chemokine ligands in macrophages and reduces T-lymphocyte recruitment in atherogenesis. Circ Res. 2008;102(2):218-225.
42. Takemura Y, et al. Adiponectin modulates inflammatory reactions via calreticulin receptor-dependent clearance of early apoptotic bodies. J Clin Invest. 2007;117(2):375-386.
43. Furuhashi M, Fucho R, Görgün CZ, Tuncman G, Cao H, Hotamisligil GS. Adipocyte/macrophage fatty acid-binding proteins contribute to metabolic deterioration through actions in both macrophages and adipocytes in mice. J Clin Invest. 2008;118(7):2640-2650.
44. Krieger M, Herz J. Structures and functions of multiligand lipoprotein receptors: Macrophage scavenger receptors and LDL receptor-related protein (LRP). Ann Rev Biochem. 1994;63:601-637.
45. Brown GO, Gordon S. Immune recognition. A new receptor for beta-glucans. Nature. 2001;413(6851):36-37.
46. Li Y, et al. Extracellular Nampt promotes macrophage survival via a nonenzymatic interleukin-6/STAT3 signaling mechanism. J Biol Chem. 2008;283(50):34833-34843.
47. Kang K, et al. Adipocyte-derived Th2 cytokines and myeloid PPARdelta regulate macrophage polarization and insulin sensitivity. Cell Metab. 2008;7(6):485-495.
48. Chen N, Liu L, Zhang Y, Ginsberg HN, Yu YH. Whole-body insulin resistance in the absence of obesity in FVB mice with overexpression of Dgat1 in adipose tissue. Diabetes. 2005;54(12):3379-3386.
49. Suganami T, et al. Activating transcription factor 3 constitutes a negative feedback mechanism that attenuates saturated Fatty acid/toll-like receptor 4 signaling and macrophage activation in obese adipose tissue. Circ Res. 2009;105(1):25-32.
50. Boradaile NM, et al. A critical role for eukaryotic elongation factor 1A-1 in lipotoxic cell death. Mol Biol Cell. 2006;17(2):770-778.
51. Cunha DA, et al. Initiation and execution of lipotoxic ER stress in pancreatic beta-cells. J Cell Sci. 2008;121(Pt 14):2308-2318.
52. Guo W, Wong S, Xie W, Lei T, Luo Z. Palmitate modulates intracellular signaling, induces endoplasmic reticulum stress, and causes apoptosis in mouse 3T3-L1 and rat primary preadipocytes. Am J Physiol Endocrinol Metab. 2007;293(2):E576-E586.
53. Ron D, Walter P. Signal integration in the endoplasmic reticulum unfolded protein response. Nat Rev Mol Cell Biol. 2007;8(7):519-529.
54. Mills CD, Kincaid K, Alt JM, Heilman MJ, Hill AM. M-1/M-2 macrophages and the Th1/Th2 paradigm. J Immunol. 2000;164(12):6166-6173.
55. Pascual G, et al. A SUMOylation-dependent pathway mediates transrepression of inflammatory response genes by PPAR-gamma. Nature. 2005;437(7059):759-763.
56. Chen HC, et al. Increased insulin and leptin sensitivity in mice lacking acyl CoA:diacylglycerol acyltransferase 1. J Clin Invest. 2002;109(8):1049-1055.
57. Buhman KK, et al. DGAT1 is not essential for intestinal triacylglycerol absorption or chylomicron synthesis. J Biol Chem. 2002;277(28):25474- 25479.
58. Zhao G, et al. Validation of diacyl glycerolacyltransferase I as a novel target for the treatment of obesity and dyslipidemia using a potent and selective small molecule inhibitor. J Med Chem. 2008;51(3):380-383.
59. Snyder F, Stephens NA. A simplified spectrophotometric determination of ester groups in lipids. Biochim Biophys Acta. 1959;34:244-245.
60. Lee S, et al. Comparison between surrogate indexes of insulin sensitivity and resistance and hyperinsulinemic euglycemic clamp estimates in mice. Am J Physiol Endocrinol Metab. 2008;294(2):E261-E270.