Pnpla3/adiponutrin deficiency in mice does not contribute to fatty liver disease or metabolic syndrome

Journal of Lipid Research

Volumn 52, Issue 2, 2011, Pages 318-329

  Basantani, Mahesh K ^a   Sitnick, Mitch T ^a   Cai, Lingzhi ^a   Brenner, Daniel S ^b   Gardner, Noah P ^b   Li, John Zhong ^c   Schoiswohl, Gabriele ^d   Yang, Kui ^e   Kumari, Manju ^d   Gross, Richard W ^e   Zechner, Rudolf ^d   Kershaw, Erin E ^a,b  

^a UNIVERSITY OF PITTSBURGH SCHOOL OF MEDICINE   (United States)

^b BETH ISRAEL DEACONESS MEDICAL CENTER   (United States)

^c UNIVERSITY OF TEXAS SOUTHWESTERN MEDICAL CENTER   (United States)

^d UNIVERSITY OF GRAZ   (Austria)

^e WASHINGTON UNIVERSITY SCHOOL OF MEDICINE   (United States)

Author keywords

Calcium independent phospholipase A2 epsilon; Insulin resistance; Patatin like phospholipase domain containing 3

Indexed keywords

ACYLTRANSFERASE; CALCIUM INDEPENDENT PHOSPHOLIPASE A2; CALCIUM INDEPENDENT PHOSPHOLIPASE A2 EPSILON; GLUCOSE; LIPID; LIVER X RECEPTOR; MESSENGER RNA; SUCROSE; TRIACYLGLYCEROL LIPASE; UNCLASSIFIED DRUG;

ADIPOSE TISSUE; ANIMAL CELL; ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; ARTICLE; CARBOHYDRATE DIET; CONTROLLED STUDY; DISEASE ASSOCIATION; ENERGY BALANCE; ENZYME ACTIVITY; ENZYME METABOLISM; FATTY LIVER; FOOD INTAKE; GENE DELETION; GLUCOSE HOMEOSTASIS; LIPID HYDROLYSIS; LIVER PARENCHYMA; MALE; METABOLIC SYNDROME X; MOUSE; NONHUMAN; OBESITY; PHENOTYPE; PRIORITY JOURNAL; PROTEIN DEFICIENCY; PROTEIN EXPRESSION; RECEPTOR BLOCKING;

ADIPOSE TISSUE; ANIMALS; ENERGY METABOLISM; FATTY LIVER; MALE; METABOLIC SYNDROME X; MICE; MICE, KNOCKOUT; PHOSPHOLIPASES A2, CALCIUM-INDEPENDENT; TRIGLYCERIDES;

EID: 78751489992     PISSN: 00222275     EISSN: 15397262     Source Type: Journal    
DOI: 10.1194/jlr.M011205     Document Type: Article

References (68)

1. Cornier, M. A., D. Dabelea, T. L. Hernandez, R. C. Lindstrom, A. J. Steig, N. R. Stob, R. E. Van Pelt, H. Wang, and R. H. Eckel. 2008. The metabolic syndrome. Endocr. Rev. 29: 777-822.
2. Schaffer, J. E. 2003. Lipotoxicity: when tissues overeat. Curr. Opin. Lipidol. 14: 281-287.
3. Unger, R. H. 2003. Minireview: weapons of lean body mass destruction: the role of ectopic lipids in the metabolic syndrome. Endocrinology. 144: 5159-5165.
4. Stefan, N., K. Kantartzis, and H. U. Haring. 2008. Causes and metabolic consequences of Fatty liver. Endocr. Rev. 29: 939-960.
5. Marchesini, G., M. Brizi, G. Bianchi, S. Tomassetti, E. Bugianesi, M. Lenzi, A. J. McCullough, S. Natale, G. Forlani, and N. Melchionda. 2001. Nonalcoholic fatty liver disease: a feature of the metabolic syndrome. Diabetes. 50: 1844-1850.
6. Kotronen, A., and H. Yki-Jarvinen. 2008. Fatty liver: a novel component of the metabolic syndrome. Arterioscler. Thromb. Vasc. Biol. 28: 27-38.
7. Angulo, P. 2002. Nonalcoholic fatty liver disease. N. Engl. J. Med. 346: 1221-1231.
8. Browning, J. D., L. S. Szczepaniak, R. Dobbins, P. Nuremberg, J. D. Horton, J. C. Cohen, S. M. Grundy, and H. H. Hobbs. 2004. Prevalence of hepatic steatosis in an urban population in the United States: impact of ethnicity. Hepatology. 40: 1387-1395.
9. Kienesberger, P. C., M. Oberer, A. Lass, and R. Zechner. 2009. Mammalian patatin domain containing proteins: a family with diverse lipolytic activities involved in multiple biological functions. J. Lipid Res. 50 (Suppl): S63-S68.
10. Romeo, S., J. Kozlitina, C. Xing, A. Pertsemlidis, D. Cox, L. A. Pennacchio, E. Boerwinkle, J. C. Cohen, and H. H. Hobbs. 2008. Genetic variation in PNPLA3 confers susceptibility to nonalcoholic fatty liver disease. Nat. Genet. 40: 1461-1465.
11. Yuan, X., D. Waterworth, J. R. Perry, N. Lim, K. Song, J. C. Chambers, W. Zhang, P. Vollenweider, H. Stirnadel, T. Johnson, et al. 2008. Population-based genome-wide association studies reveal six loci influencing plasma levels of liver enzymes. Am. J. Hum. Genet. 83: 520-528.
12. Kotronen, A., L. E. Johansson, L. M. Johansson, C. Roos, J. Westerbacka, A. Hamsten, R. Bergholm, P. Arkkila, J. Arola, T. Kiviluoto, et al. 2009. A common variant in PNPLA3, which encodes adiponutrin, is associated with liver fat content in humans. Diabetologia. 52: 1056-1060.
13. Johansson, L. E., L. M. Johansson, P. Danielsson, S. Norgren, S. Johansson, C. Marcus, and M. Ridderstrale. 2009. Genetic variance in the adiponutrin gene family and childhood obesity. PLoS ONE. 4: e5327.
14. Sookoian, S., G. O. Castano, A. L. Burgueno, T. F. Gianotti, M. S. Rosselli, and C. J. Pirola. 2009. A nonsynonymous gene variant in the adiponutrin gene is associated with nonalcoholic fatty liver disease severity. J. Lipid Res. 50: 2111-2116.
15. Kollerits, B., S. Coassin, S. Kiechl, S. C. Hunt, B. Paulweber, J. Willeit, A. Brandstatter, C. Lamina, T. D. Adams, and F. Kronenberg. 2010. A common variant in the adiponutrin gene influences liver enzyme values. J. Med. Genet. 47: 116-119.
16. Kollerits, B., S. Coassin, N. D. Beckmann, A. Teumer, S. Kiechl, A. Doring, M. Kavousi, S. C. Hunt, C. Lamina, B. Paulweber, et al. 2009. Genetic evidence for a role of adiponutrin in the metabolism of apolipoprotein B-containing lipoproteins. Hum. Mol. Genet. 18: 4669-4676.
17. Liang, H., M. Cai, Y. Bi, Y. Zhu, J. Yan, and J. Weng. 2009. A single nucleotide polymorphism (SNP) rs2072907 in the adiponutrin gene (ADPN) was not associated with obesity and type 2 diabetes in Chinese population. Diabetes Res. Clin. Pract. 85: e37-e39.
18. Kantartzis, K., A. Peter, F. Machicao, J. Machann, S. Wagner, I. Konigsrainer, A. Konigsrainer, F. Schick, A. Fritsche, H. U. Haring, et al. 2009. Dissociation between fatty liver and insulin resistance in humans carrying a variant of the patatin-like phospholipase 3 gene. Diabetes. 58: 2616-2623.
19. Romeo, S., F. Sentinelli, S. Dash, G. S. Yeo, D. B. Savage, F. Leonetti, D. Capoccia, M. Incani, C. Maglio, M. Iacovino, et al. 2009. Morbid obesity exposes the association between PNPLA3 I148M (rs738409) and indices of hepatic injury in individuals of European descent. Int. J. Obes. (Lond). 34: 190-194.
20. Valenti, L., A. Al-Serri, A. K. Daly, E. Galmozzi, R. Rametta, P. Dongiovanni, V. Nobili, E. Mozzi, G. Roviaro, E. Vanni, et al. 2010. Homozygosity for the patatin-like phospholipase-3/adiponutrin I148M polymorphism influences liver fibrosis in patients with nonalcoholic fatty liver disease. Hepatology. 51: 1209-1217.
21. Romeo, S., F. Sentinelli, V. M. Cambuli, M. Incani, T. Congiu, V. Matta, S. Pilia, I. Huang-Doran, E. Cossu, S. Loche, et al. 2010. The 148M allele of the PNPLA3 gene is associated with indices of liver damage early in life. J. Hepatol. 53: 335-338.
22. Speliotes, E. K., J. L. Butler, C. D. Palmer, B. F. Voight, and J. N. Hirschhorn. 2010. PNPLA3 variants specifically confer increased risk for histologic nonalcoholic fatty liver disease but not metabolic disease. Hepatology. 52: 904-912.
23. Valenti, L., A. Alisi, E. Galmozzi, A. Bartuli, B. Del Menico, A. Alterio, P. Dongiovanni, S. Fargion, and V. Nobili. 2010. I148M patatin-like phospholipase domain-containing 3 gene variant and severity of pediatric nonalcoholic fatty liver disease. Hepatology.
24. Rotman, Y., C. Koh, J. M. Zmuda, D. E. Kleiner, and T. J. Liang. 2010. The association of genetic variability in patatin-like phospholipase domain-containing protein 3 (PNPLA3) with histological severity of nonalcoholic fatty liver disease. Hepatology. 52: 894-903.
25. Johansson, L. E., J. Hoffstedt, H. Parikh, E. Carlsson, M. Wabitsch, A. G. Bondeson, J. Hedenbro, H. Tornqvist, L. Groop, and M. Ridderstrale. 2006. Variation in the adiponutrin gene influences its expression and associates with obesity. Diabetes. 55: 826-833.
26. Johansson, L. E., U. Lindblad, C. A. Larsson, L. Rastam, and M. Ridderstrale. 2008. Polymorphisms in the adiponutrin gene are associated with increased insulin secretion and obesity. Eur. J. Endocrinol. 159: 577-583.
27. Baulande, S., F. Lasnier, M. Lucas, and J. Pairault. 2001. Adiponutrin, a transmembrane protein corresponding to a novel dietary- and obesity-linked mRNA specifically expressed in the adipose lineage. J. Biol. Chem. 276: 33336-33344.
28. Lake, A. C., Y. Sun, J. L. Li, J. E. Kim, J. W. Johnson, D. Li, T. Revett, H. H. Shih, W. Liu, J. E. Paulsen, et al. 2005. Expression, regulation, and triglyceride hydrolase activity of Adiponutrin family members. J. Lipid Res. 46: 2477-2487.
29. Caimari, A., P. Oliver, and A. Palou. 2007. Regulation of adiponutrin expression by feeding conditions in rats is altered in the obese state. Obesity (Silver Spring). 15: 591-599. (Pubitemid 46643311)
30. Polson, D. A., and M. P. Thompson. 2003. Adiponutrin mRNA expression in white adipose tissue is rapidly induced by meal-feeding a high-sucrose diet. Biochem. Biophys. Res. Commun. 301: 261-266.
31. Wiesner, G., B. A. Morash, E. Ur, and M. Wilkinson. 2004. Food restriction regulates adipose-specific cytokines in pituitary gland but not in hypothalamus. J. Endocrinol. 180: R1-R6.
32. Polson, D. A., and M. P. Thompson. 2004. Macronutrient composition of the diet differentially affects leptin and adiponutrin mRNA expression in response to meal feeding. J. Nutr. Biochem. 15: 242-246.
33. Liu, Y. M., M. Moldes, J. P. Bastard, E. Bruckert, N. Viguerie, B. Hainque, A. Basdevant, D. Langin, J. Pairault, and K. Clement. 2004. Adiponutrin: A new gene regulated by energy balance in human adipose tissue. J. Clin. Endocrinol. Metab. 89: 2684-2689.
34. Bertile, F., and T. Raclot. 2004. Differences in mRNA expression of adipocyte-derived factors in response to fasting, refeeding and leptin. Biochim. Biophys. Acta. 1683: 101-109.
35. Kershaw, E. E., J. K. Hamm, L. A. Verhagen, O. Peroni, M. Katic, and J. S. Flier. 2006. Adipose triglyceride lipase: function, regulation by insulin, and comparison with adiponutrin. Diabetes. 55: 148-157.
36. Huong, D. T., and T. Ide. 2008. Dietary lipoic acid-dependent changes in the activity and mRNA levels of hepatic lipogenic enzymes in rats. Br. J. Nutr. 100: 79-87.
37. Hoekstra, M., Z. Li, J. K. Kruijt, M. Van Eck, T. J. Van Berkel, and J. Kuiper. 2010. The expression level of non-alcoholic fatty liver disease-related gene PNPLA3 in hepatocytes is highly influenced by hepatic lipid status. J. Hepatol. 52: 244-251.
38. Huang, Y. H. S., J. Z. Li, Y. K. Seo, T. G. Osborne, J. C. Cohen, and H. H. Hobbs. 2010. A feed-forward loop amplifies nutritional regulation of PNPLA3. Proc. Natl. Acad. Sci. U S A. 107: 7892-7897.
39. Moldes, M., G. Beauregard, M. Faraj, N. Peretti, P. H. Ducluzeau, M. Laville, R. Rabasa-Lhoret, H. Vidal, and K. Clement. 2006. Adiponutrin gene is regulated by insulin and glucose in human adipose tissue. Eur. J. Endocrinol. 155: 461-468.
40. Faraj, M., G. Beauregard, E. Loizon, M. Moldes, K. Clement, Y. Tahiri, K. Cianflone, H. Vidal, and R. Rabasa-Lhoret. 2006. Insulin regulation of gene expression and concentrations of white adipose tissue-derived proteins in vivo in healthy men: relation to adiponutrin. J. Endocrinol. 191: 427-435.
41. Calvo, R. M., and M. J. Obregon. 2009. Tri-iodothyronine upregulates adiponutrin mRNA expression in rat and human adipocytes. Mol. Cell. Endocrinol. 311: 39-46.
42. Polson, D., and M. Thompson. 2003. Adiponutrin gene expression in 3T3-L1 adipocytes is downregulated by troglitazone. Horm. Metab. Res. 35: 508-510. (Pubitemid 37204570)
43. Jenkins, C. M., D. J. Mancuso, W. Yan, H. F. Sims, B. Gibson, and R. W. Gross. 2004. 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. 279: 48968-48975.
44. He, S., C. McPhaul, J. Z. Li, R. Garuti, L. Kinch, N. V. Grishin, J. C. Cohen, and H. H. Hobbs. 2010. A sequence variation (I148M) in PNPLA3 associated with nonalcoholic fatty liver disease disrupts triglyceride hydrolysis. J. Biol. Chem. 285: 6706-6715.
45. Liu, P., N. A. Jenkins, and N. G. Copeland. 2003. A highly efficient recombineering-based method for generating conditional knockout mutations. Genome Res. 13: 476-484.
46. Lee, E. C., D. Yu, J. Martinez de Velasco, L. Tessarollo, D. A. Swing, D. L. Court, N. A. Jenkins, and N. G. Copeland. 2001. A highly efficient Escherichia coli-based chromosome engineering system adapted for recombinogenic targeting and subcloning of BAC DNA. Genomics. 73: 56-65.
47. Kershaw, E. E., N. M. Morton, H. Dhillon, L. Ramage, J. R. Seckl, and J. S. Flier. 2005. Adipocyte-specific glucocorticoid inactivation protects against diet-induced obesity. Diabetes. 54: 1023-1031.
48. Repa, J. J., S. D. Turley, J. A. Lobaccaro, J. Medina, L. Li, K. Lustig, B. Shan, R. A. Heyman, J. M. Dietschy, and D. J. Mangelsdorf. 2000. Regulation of absorption and ABC1-mediated efflux of cholesterol by RXR heterodimers. Science 289: 1524-1529.
49. Schultz, J. R., H. Tu, A. Luk, J. J. Repa, J. C. Medina, L. Li, S. Schwendner, S. Wang, M. Thoolen, D. J. Mangelsdorf, et al. 2000. Role of LXRs in control of lipogenesis. Genes Dev. 14: 2831-2838.
50. Yu, L., J. York, K. von Bergmann, D. Lutjohann, J. C. Cohen, and H. H. Hobbs. 2003. Stimulation of cholesterol excretion by the liver X receptor agonist requires ATP-binding cassette transporters G5 and G8. J. Biol. Chem. 278: 15565-15570.
51. Haemmerle, G., R. Zimmermann, M. Hayn, C. Theussl, G. Waeg, E. Wagner, W. Sattler, T. M. Magin, E. F. Wagner, and R. Zechner. 2002. Hormone-sensitive lipase deficiency in mice causes diglyceride accumulation in adipose tissue, muscle, and testis. J. Biol. Chem. 277: 4806-4815.
52. Holm, C., and T. Osterlund. Hormone-sensitive lipase and neutral cholesterl ester lipase. In: Doolittle, M., and R. Reue (eds.), Methods in molecular biology: lipase and phospholipase protocols. Humana Press, Totowa, NJ; 1998: 109-121.
53. Schweiger, M., R. Schreiber, G. Haemmerle, A. Lass, C. Fledelius, P. Jacobsen, H. Tornqvist, R. Zechner, and R. Zimmermann. 2006. Adipose triglyceride lipase and hormone-sensitive lipase are the major enzymes in adipose tissue triacylglycerol catabolism. J. Biol. Chem. 281: 40236-40241.
54. Folch, J., M. Lees, and G. H. Sloane Stanley. 1957. A simple method for the isolation and purification of total lipides from animal tissues. J. Biol. Chem. 226: 497-509.
55. Koopman, R., G. Schaart, and M. K. Hesselink. 2001. Optimisation of oil red O staining permits combination with immunofluorescence and automated quantification of lipids. Histochem. Cell Biol. 116: 63-68.
56. Shimano, H., J. D. Horton, R. E. Hammer, I. Shimomura, M. S. Brown, and J. L. Goldstein. 1996. Overproduction of cholesterol and fatty acids causes massive liver enlargement in transgenic mice expressing truncated SREBP-1a. J. Clin. Invest. 98: 1575-1584.
57. Lowenstein, J. M., H. Brunengraber, and M. Wadke. 1975. Measurement of rates of lipogenesis with deuterated and tritiated water. Methods Enzymol. 35: 279-287.
58. Dietschy, J. M., and D. K. Spady. 1984. Measurement of rates of cholesterol synthesis using tritiated water. J. Lipid Res. 25: 1469-1476.
59. Yang, K., H. Cheng, R. W. Gross, and X. Han. 2009. Automated lipid identification and quantification by multidimensional mass spectrometry-based shotgun lipidomics. Anal. Chem. 81: 4356-4368.
60. Han, X., and R. W. Gross. 2001. Quantitative analysis and molecular species fingerprinting of triacylglyceride molecular species directly from lipid extracts of biological samples by electrospray ionization tandem mass spectrometry. Anal. Biochem. 295: 88-100.
61. Bligh, E. G., and E. J. Dyer. 1959. A rapid method for total lipid extraction and purification. Can. J. Biochem. Physiol. 37: 911-917.
62. Kienesberger, P. C., D. Lee, T. Pulinilkunnil, D. S. Brenner, L. Cai, C. Magnes, H. C. Koefeler, I. E. Streith, G. N. Rechberger, G. Haemmerle, et al. 2009. Adipose triglyceride lipase deficiency causes tissue-specific changes in insulin signaling. J. Biol. Chem. 284: 30218-30229.
63. Bustin, S. A., V. Benes, J. A. Garson, J. Hellemans, J. Huggett, M. Kubista, R. Mueller, T. Nolan, M. W. Pfaffl, G. L. Shipley, et al. 2009. The MIQE guidelines: minimum information for publication of quantitative real-time PCR experiments. Clin. Chem. 55: 611-622.
64. Zimmermann, R., J. G. Strauss, G. Haemmerle, G. Schoiswohl, R. Birner-Gruenberger, M. Riederer, A. Lass, G. Neuberger, F. Eisenhaber, A. Hermetter, et al. 2004. Fat mobilization in adipose tissue is promoted by adipose triglyceride lipase. Science 306: 1383-1386.
65. Wilson, P. A., S. D. Gardner, N. M. Lambie, S. A. Commans, and D. J. Crowther. 2006. Characterization of the human patatin-like phospholipase family. J. Lipid Res. 47: 1940-1949.
66. Chen, W., B. Chang, L. Li, and L. Chan. 2010. Patatin-like phospholipase domain-containing 3/adiponutrin deficiency in mice is not associated with fatty liver disease. Hepatology. 52: 1134-1142.
67. Lim, J. S., M. Mietus-Snyder, A. Valente, J. M. Schwarz, and R. H. Lustig. 2010. The role of fructose in the pathogenesis of NAFLD and the metabolic syndrome. Nat. Rev. Gastroenterol. Hepatol. 7: 251-264.
68. Gao, J. G., and M. Simon. 2007. A comparative study of human GS2, its paralogues, and its rat orthologue. Biochem. Biophys. Res. Commun. 360: 501-506.