Role of metabolic lipases and lipolytic metabolites in the pathogenesis of NAFLD

Trends in Endocrinology and Metabolism

Volumn 25, Issue 11, 2014, Pages 576-585

  Fuchs, Claudia D ^a   Claudel, Thierry ^a   Trauner, Michael ^a  

^a MEDICAL UNIVERSITY OF VIENNA   (Austria)

Author keywords

[No Author keywords available]

Indexed keywords

CELL NUCLEUS RECEPTOR; FARNESOID X RECEPTOR; FATTY ACID; LIVER X RECEPTOR; PEROXISOME PROLIFERATOR ACTIVATED RECEPTOR; TRIACYLGLYCEROL LIPASE; CELL RECEPTOR; CHOLESTEROL ESTERASE; FARNESOID X-ACTIVATED RECEPTOR; PNPLA2 PROTEIN, HUMAN;

DISEASE COURSE; GENE; GENETIC POLYMORPHISM; HUMAN; INFLAMMATION; LIPOLYSIS; LIVER FIBROSIS; LIVER INJURY; METABOLITE; NONALCOHOLIC FATTY LIVER; NONHUMAN; PATHOGENESIS; PNPLA3 GENE; PRIORITY JOURNAL; REVIEW; SIGNAL TRANSDUCTION; TISSUE SPECIFICITY; ANIMAL; ENZYMOLOGY; GENETICS; LIVER; METABOLISM; NON-ALCOHOLIC FATTY LIVER DISEASE; PHYSIOLOGY;

ANIMALS; DISEASE PROGRESSION; HUMANS; LIPASE; LIPOLYSIS; LIVER; NON-ALCOHOLIC FATTY LIVER DISEASE; RECEPTORS, CYTOPLASMIC AND NUCLEAR; STEROL ESTERASE;

EID: 84927671391     PISSN: 10432760     EISSN: 18793061     Source Type: Journal    
DOI: 10.1016/j.tem.2014.08.001     Document Type: Review

References (107)

1. Cohen J.C., et al. Human fatty liver disease: old questions and new insights. Science 2011, 332:1519-1523.
2. Trauner M., et al. Fatty liver and lipotoxicity. Biochim. Biophys. Acta 2010, 1801:299-310.
3. Stefan N., et al. Dissociation between fatty liver and insulin resistance: the role of adipose triacylglycerol lipase. Diabetologia 2011, 54:7-9.
4. Utzschneider K.M., Kahn S.E. The role of insulin resistance in nonalcoholic fatty liver disease. J. Clin. Endocrinol. Metab. 2006, 91:4753-4761.
5. Bertolani C., Marra F. The role of adipokines in liver fibrosis. Pathophysiology 2008, 15:91-101.
6. Anderson N., Borlak J. Molecular mechanisms and therapeutic targets in steatosis and steatohepatitis. Pharmacol. Rev. 2008, 60:311-357.
7. Postic C., Girard J. Contribution of de novo fatty acid synthesis to hepatic steatosis and insulin resistance: lessons from genetically engineered mice. J. Clin. Invest. 2008, 118:829-838.
8. Tilg H., Moschen A.R. Evolution of inflammation in nonalcoholic fatty liver disease: the multiple parallel hits hypothesis. Hepatology 2010, 52:1836-1846.
9. Neuschwander-Tetri B.A. Hepatic lipotoxicity and the pathogenesis of nonalcoholic steatohepatitis: the central role of nontriglyceride fatty acid metabolites. Hepatology 2010, 52:774-788.
10. Evans R.M., Mangelsdorf D.J. Nuclear receptors, RXR, and the big bang. Cell 2014, 157:255-266.
11. Bookout A.L., et al. Anatomical profiling of nuclear receptor expression reveals a hierarchical transcriptional network. Cell 2006, 126:789-799.
12. Fuchs C., et al. Bile acid-mediated control of liver triglycerides. Semin. Liver Dis. 2013, 33:330-432.
13. Browning J.D., Horton J.D. Molecular mediators of hepatic steatosis and liver injury. J. Clin. Invest. 2004, 114:147-152.
14. Snel M., et al. Ectopic fat and insulin resistance: pathophysiology and effect of diet and lifestyle interventions. Int. J. Endocrinol. 2012, 2012:983814.
15. Samuel V.T., Shulman G.I. Mechanisms for insulin resistance: common threads and missing links. Cell 2012, 148:852-871.
16. Romeo S., et al. Genetic variation in PNPLA3 confers susceptibility to nonalcoholic fatty liver disease. Nat. Genet. 2008, 40:1461-1465.
17. Sevastianova K., et al. Genetic variation in PNPLA3 (adiponutrin) confers sensitivity to weight loss-induced decrease in liver fat in humans. Am. J. Clin. Nutr. 2011, 94:104-111.
18. Hyysalo J., et al. Genetic variation in PNPLA3 but not APOC3 influences liver fat in non-alcoholic fatty liver disease. J. Gastroenterol. Hepatol. 2012, 27:951-956.
19. Sookoian S., Pirola C.J. Meta-analysis of the influence of I148M variant of patatin-like phospholipase domain containing 3 gene (PNPLA3) on the susceptibility and histological severity of nonalcoholic fatty liver disease. Hepatology 2011, 53:1883-1894.
20. Kantartzis K., et al. Dissociation between fatty liver and insulin resistance in humans carrying a variant of the patatin-like phospholipase 3 gene. Diabetes 2009, 58:2616-2623.
21. Kotronen A., et al. A common variant in PNPLA3, which encodes adiponutrin, is associated with liver fat content in humans. Diabetologia 2009, 52:1056-1060.
22. Speliotes E.K., et al. PNPLA3 variants specifically confer increased risk for histologic nonalcoholic fatty liver disease but not metabolic disease. Hepatology 2010, 52:904-912.
23. He S., et al. A sequence variation (I148M) in PNPLA3 associated with nonalcoholic fatty liver disease disrupts triglyceride hydrolysis. J. Biol. Chem. 2010, 285:6706-6715.
24. Qiao A., et al. Mouse patatin-like phospholipase domain-containing 3 influences systemic lipid and glucose homeostasis. Hepatology 2011, 54:509-5021.
25. Basantani M.K., et al. Pnpla3/Adiponutrin deficiency in mice does not contribute to fatty liver disease or metabolic syndrome. J. Lipid Res. 2011, 52:318-329.
26. Chen W., et al. Patatin-like phospholipase domain-containing 3/adiponutrin deficiency in mice is not associated with fatty liver disease. Hepatology 2010, 52:1134-1142.
27. Valenti L., et al. Homozygosity for the patatin-like phospholipase-3/adiponutrin I148M polymorphism influences liver fibrosis in patients with nonalcoholic fatty liver disease. Hepatology 2010, 51:1209-1217.
28. Pirazzi C., et al. PNPLA3 has retinyl-palmitate lipase activity in human hepatic stellate cells. Hum. Mol. Genet. 2014, 23:4077-4085.
29. Tian C., et al. Variant in PNPLA3 is associated with alcoholic liver disease. Nat. Genet. 2010, 42:21-23.
30. Valenti L., et al. Modulation of the effect of PNPLA3 I148M mutation on steatosis and liver damage by alcohol intake in patients with chronic hepatitis C. J. Hepatol. 2011, 55:1470-1471.
31. Jha P., et al. Role of adipose triglyceride lipase (PNPLA2) in protection from hepatic inflammation in mouse models of steatohepatitis and endotoxemia. Hepatology 2014, 59:858-869.
32. Schweiger M., et al. Neutral lipid storage disease: genetic disorders caused by mutations in adipose triglyceride lipase/PNPLA2 or CGI-58/ABHD5. Am. J. Physiol. Endocrinol. Metab. 2009, 297:E289-E296.
33. Wu J.W., et al. Deficiency of liver adipose triglyceride lipase in mice causes progressive hepatic steatosis. Hepatology 2011, 54:122-132.
34. Ong K.T., et al. Hepatic ATGL knockdown uncouples glucose intolerance from liver TAG accumulation. FASEB J. 2013, 27:313-321.
35. Fuchs C.D., et al. Absence of adipose triglyceride lipase protects from hepatic endoplasmic reticulum stress in mice. Hepatology 2012, 56:270-280.
36. Guo F., et al. Deficiency of liver comparative gene identification-58 causes steatohepatitis and fibrosis in mice. J. Lipid Res. 2013, 54:2109-2120.
37. Young S.G., Zechner R. Biochemistry and pathophysiology of intravascular and intracellular lipolysis. Genes Dev. 2013, 27:459-484.
38. Albert J.S., et al. Null mutation in hormone-sensitive lipase gene and risk of type 2 diabetes. N. Engl. J. Med. 2014, 370:2307-2315.
39. Haemmerle G., et al. Hormone-sensitive lipase deficiency in mice causes diglyceride accumulation in adipose tissue, muscle, and testis. J. Biol. Chem. 2002, 277:4806-4815.
40. Zimmermann R., et al. Decreased fatty acid esterification compensates for the reduced lipolytic activity in hormone-sensitive lipase-deficient white adipose tissue. J. Lipid Res. 2003, 44:2089-2099.
41. Shen W.J., et al. Hormone-sensitive lipase modulates adipose metabolism through PPARgamma. Biochim. Biophys. Acta 2011, 1811:9-16.
42. Cinti S., et al. Adipocyte death defines macrophage localization and function in adipose tissue of obese mice and humans. J. Lipid Res. 2005, 46:2347-2355.
43. Reid B.N., et al. Hepatic overexpression of hormone-sensitive lipase and adipose triglyceride lipase promotes fatty acid oxidation, stimulates direct release of free fatty acids, and ameliorates steatosis. J. Biol. Chem. 2008, 283:13087-13099.
44. Quiroga A.D., Lehner R. Liver triacylglycerol lipases. Biochim. Biophys. Acta 2012, 1821:762-769.
45. Ibrahim S.H., et al. Mechanisms of lipotoxicity in NAFLD and clinical implications. J. Pediatr. Gastroenterol. Nutr. 2011, 53:131-140.
46. Listenberger L.L., et al. Triglyceride accumulation protects against fatty acid-induced lipotoxicity. Proc. Natl. Acad. Sci. U.S.A. 2003, 100:3077-3082.
47. Glass C.K., Olefsky J.M. Inflammation and lipid signaling in the etiology of insulin resistance. Cell Metab. 2012, 15:635-645.
48. Seimon T.A., et al. Atherogenic lipids and lipoproteins trigger CD36-TLR2-dependent apoptosis in macrophages undergoing endoplasmic reticulum stress. Cell Metab. 2010, 12:467-482.
49. Stewart C.R., et al. CD36 ligands promote sterile inflammation through assembly of a Toll-like receptor 4 and 6 heterodimer. Nat. Immunol. 2010, 11:155-161.
50. Wong S.W., et al. Fatty acids modulate Toll-like receptor 4 activation through regulation of receptor dimerization and recruitment into lipid rafts in a reactive oxygen species-dependent manner. J. Biol. Chem. 2009, 284:27384-27392.
51. Pal D., et al. Fetuin-A acts as an endogenous ligand of TLR4 to promote lipid-induced insulin resistance. Nat. Med. 2012, 18:1279-1285.
52. Wen H., et al. Fatty acid-induced NLRP3-ASC inflammasome activation interferes with insulin signaling. Nat. Immunol. 2011, 12:408-4015.
53. Henao-Mejia J., et al. Inflammasome-mediated dysbiosis regulates progression of NAFLD and obesity. Nature 2012, 482:179-185.
54. Zechner R., et al. Fat signals - lipases and lipolysis in lipid metabolism and signaling. Cell Metab. 2012, 15:279-291.
55. Deckelbaum R.J., et al. n-3 fatty acids and gene expression. Am. J. Clin. Nutr. 2006, 83(Suppl.):1520S-1525S.
56. Oh D.Y., et al. GPR120 is an omega-3 fatty acid receptor mediating potent anti-inflammatory and insulin-sensitizing effects. Cell 2010, 142:687-698.
57. Kumashiro N., et al. Cellular mechanism of insulin resistance in nonalcoholic fatty liver disease. Proc. Natl. Acad. Sci. U.S.A. 2011, 108:16381-16385.
58. Samuel V.T., et al. Lipid-induced insulin resistance: unravelling the mechanism. Lancet 2010, 375:2267-2277.
59. Jornayvaz F.R., Shulman G.I. Diacylglycerol activation of protein kinase Cepsilon and hepatic insulin resistance. Cell Metab. 2012, 15:574-584.
60. Benhamed F., et al. The lipogenic transcription factor ChREBP dissociates hepatic steatosis from insulin resistance in mice and humans. J. Clin. Invest. 2012, 122:2176-2194.
61. Cantley J.L., et al. CGI-58 knockdown sequesters diacylglycerols in lipid droplets/ER-preventing diacylglycerol-mediated hepatic insulin resistance. Proc. Natl. Acad. Sci. U.S.A. 2013, 110:1869-1874.
62. Ganong B.R., et al. Specificity and mechanism of protein kinase C activation by sn-1,2-diacylglycerols. Proc. Natl. Acad. Sci. U.S.A. 1986, 83:1184-2118.
63. Ebeling J.G., et al. Diacylglycerols mimic phorbol diester induction of leukemic cell differentiation. Proc. Natl. Acad. Sci. U.S.A. 1985, 82:815-819.
64. Simonen P., et al. Cholesterol synthesis is increased and absorption decreased in non-alcoholic fatty liver disease independent of obesity. J. Hepatol. 2011, 54:153-159.
65. Enjoji M., et al. Nutrition and nonalcoholic fatty liver disease: the significance of cholesterol. Int. J. Hepatol. 2012, 00:925807.
66. Subramanian S., et al. Dietary cholesterol exacerbates hepatic steatosis and inflammation in obese LDL receptor-deficient mice. J. Lipid Res. 2011, 52:1626-1635.
67. Schwabe R.F., Maher J.J. Lipids in liver disease: looking beyond steatosis. Gastroenterology 2012, 142:8-11.
68. Georgiadi A., Kersten S. Mechanisms of gene regulation by fatty acids. Adv. Nutr. Res. 2012, 3:127-134.
69. Escher P., et al. Rat PPARs: quantitative analysis in adult rat tissues and regulation in fasting and refeeding. Endocrinology 2001, 142:4195-4202.
70. Nakamura M.T., et al. Regulation of energy metabolism by long-chain fatty acids. Prog. Lipid Res. 2014, 53:124-144.
71. Haemmerle G., et al. ATGL-mediated fat catabolism regulates cardiac mitochondrial function via PPAR-alpha and PGC-1. Nat. Med. 2011, 17:1076-1085.
72. Nolan C.J., Larter C.Z. Lipotoxicity: why do saturated fatty acids cause and monounsaturates protect against it?. J. Gastroenterol. Hepatol. 2009, 24:703-706.
73. Chakravarthy M.V., et al. Identification of a physiologically relevant endogenous ligand for PPARalpha in liver. Cell 2009, 138:476-488.
74. Pirat C., et al. Targeting peroxisome proliferator-activated receptors (PPARs): development of modulators. J. Med. Chem. 2012, 55:4027-4061.
75. Zhao A., et al. Polyunsaturated fatty acids are FXR ligands and differentially regulate expression of FXR targets. DNA Cell Biol. 2004, 23:519-526.
76. Thomas C., et al. Targeting bile-acid signalling for metabolic diseases. Nat. Rev. Drug Discov. 2008, 7:678-693.
77. Watanabe M., et al. Bile acids lower triglyceride levels via a pathway involving FXR, SHP, and SREBP-1c. J. Clin. Invest. 2004, 113:1408-1418.
78. Huang J., et al. Molecular characterization of the role of orphan receptor small heterodimer partner in development of fatty liver. Hepatology 2007, 46:147-157.
79. Kozlitina J., et al. Exome-wide association study identifies a TM6SF2 variant that confers susceptibility to nonalcoholic fatty liver disease. Nat. Genet. 2014, 46:352-356.
80. Caron S., et al. Farnesoid X receptor inhibits the transcriptional activity of carbohydrate response element binding protein in human hepatocytes. Mol. Cell. Biol. 2013, 33:2202-2211.
81. Pineda Torra I., et al. Bile acids induce the expression of the human peroxisome proliferator-activated receptor alpha gene via activation of the farnesoid X receptor. Mol. Endocrinol. 2003, 17:259-272.
82. Hong C., Tontonoz P. Liver X receptors in lipid metabolism: opportunities for drug discovery. Nat. Rev. Drug Discov. 2014, 13:433-444.
83. Ren N., et al. Phenolic acids suppress adipocyte lipolysis via activation of the nicotinic acid receptor GPR109A (HM74a/PUMA-G). J. Lipid Res. 2009, 50:908-914.
84. Boden W.E., et al. Niacin in patients with low HDL cholesterol levels receiving intensive statin therapy. N. Engl. J. Med. 2011, 365:2255-2267.
85. Dowman J.K., et al. Current therapeutic strategies in non-alcoholic fatty liver disease. Diabetes Obes. Metab. 2011, 13:692-702.
86. Zelber-Sagi S., et al. A double-blind randomized placebo-controlled trial of orlistat for the treatment of nonalcoholic fatty liver disease. Clin. Gastroenterol. Hepatol. 2006, 4:639-644.
87. Hussein O., et al. Orlistat reverse fatty infiltration and improves hepatic fibrosis in obese patients with nonalcoholic steatohepatitis (NASH). Dig. Dis. Sci. 2007, 52:2512-2519.
88. Tailleux A., et al. Roles of PPARs in NAFLD: potential therapeutic targets. Biochim. Biophys. Acta 2012, 1821:809-818.
89. Peters J.M., et al. The role of peroxisome proliferator-activated receptors in carcinogenesis and chemoprevention. Nat. Rev. Cancer 2012, 12:181-195.
90. Bajaj M., et al. Effects of peroxisome proliferator-activated receptor (PPAR)-alpha and PPAR-gamma agonists on glucose and lipid metabolism in patients with type 2 diabetes mellitus. Diabetologia 2007, 50:1723-1731.
91. Staels B., et al. Hepatoprotective effects of the dual peroxisome proliferator-activated receptor alpha/delta agonist, GFT505, in rodent models of nonalcoholic fatty liver disease/nonalcoholic steatohepatitis. Hepatology 2013, 58:1941-1952.
92. Cariou B., et al. Dual peroxisome proliferator-activated receptor alpha/delta agonist GFT505 improves hepatic and peripheral insulin sensitivity in abdominally obese subjects. Diabetes Care 2013, 36:2923-2930.
93. Ratziu V. Pharmacological agents for NASH. Nat. Rev. Gastroenterol. Hepatol. 2013, 10:676-685.
94. Belfort R., et al. A placebo-controlled trial of pioglitazone in subjects with nonalcoholic steatohepatitis. N. Engl. J. Med. 2006, 355:2297-2307.
95. Sanyal A.J., et al. Pioglitazone, vitamin E, or placebo for nonalcoholic steatohepatitis. N. Engl. J. Med. 2010, 362:1675-1785.
96. Lutchman G., et al. The effects of discontinuing pioglitazone in patients with nonalcoholic steatohepatitis. Hepatology 2007, 46:424-429.
97. Balas B., et al. Pioglitazone treatment increases whole body fat but not total body water in patients with non-alcoholic steatohepatitis. J. Hepatol. 2007, 47:565-570.
98. Adams M., et al. Activators of peroxisome proliferator-activated receptor gamma have depot-specific effects on human preadipocyte differentiation. J. Clin. Invest. 1997, 100:3149-3153.
99. Mudaliar S., et al. Efficacy and safety of the farnesoid X receptor agonist obeticholic acid in patients with type 2 diabetes and nonalcoholic fatty liver disease. Gastroenterology 2013, 145:574-582.
100. Schweiger M., et al. Adipose triglyceride lipase and hormone-sensitive lipase are the major enzymes in adipose tissue triacylglycerol catabolism. J. Biol. Chem. 2006, 281:40236-40241.
101. Cao Z., et al. Monoacylglycerol lipase controls endocannabinoid and eicosanoid signaling and hepatic injury in mice. Gastroenterology 2013, 144:808-817.
102. Scherer T., et al. Brain insulin controls adipose tissue lipolysis and lipogenesis. Cell Metab. 2011, 13:183-194.
103. Jenkins C.M., et al. Identification, cloning, expression, and purification of three novel human calcium-independent phospholipase A2 family members possessing triacylglycerol lipase and acylglycerol transacylase activities. J. Biol. Chem. 2004, 279:48968-48975.
104. Kumari M., et al. Adiponutrin functions as a nutritionally regulated lysophosphatidic acid acyltransferase. Cell Metab. 2012, 15:691-702.
105. Caimari A., et al. Regulation of adiponutrin expression by feeding conditions in rats is altered in the obese state. Obesity 2007, 15:591-599.
106. Kershaw E.E., et al. Adipose triglyceride lipase: function, regulation by insulin, and comparison with adiponutrin. Diabetes 2006, 55:148-157.
107. Huang Y., et al. A feed-forward loop amplifies nutritional regulation of PNPLA3. Proc. Natl. Acad. Sci. U.S.A. 2010, 107:7892-78987.