The genetic variant I148M in PNPLA3 is associated with increased hepatic retinyl-palmitate storage in humans

Journal of Clinical Endocrinology and Metabolism

Volumn 100, Issue 12, 2015, Pages E1568-E1574

  Kovarova, Marketa ^a   Königsrainer, Ingmar ^a   Königsrainer, Alfred ^a   Machicao, Fausto ^a,b   Häring, Hans Ulrich ^a,b   Schleicher, Erwin ^a,b   Peter, Andreas ^a,b  

^a UNIVERSITY OF TÜBINGEN   (Germany)

^b GERMAN CENTER FOR DIABETES RESEARCH DZD   (Germany)

Author keywords

[No Author keywords available]

Indexed keywords

HEPATIC RETINYL PALMITATE; INSULIN; PALMITIC ACID; PNPLA3 PROTEIN; PROTEIN; UNCLASSIFIED DRUG; ADIPONUTRIN, HUMAN; FATTY ACID; MEMBRANE PROTEIN; PALMITIC ACID DERIVATIVE; RETINOID; RETINOL; TRIACYLGLYCEROL; TRIACYLGLYCEROL LIPASE;

AGED; ALLELE; ARTICLE; CAUCASIAN; CLINICAL ARTICLE; CONTROLLED STUDY; ENZYME ACTIVITY; FAT CONTENT; FEMALE; GENE; GENE SEQUENCE; GENETIC VARIABILITY; GENOTYPE; HETEROZYGOSITY; HIGH PERFORMANCE LIQUID CHROMATOGRAPHY; HOMOZYGOSITY; HUMAN; HUMAN TISSUE; IN VITRO STUDY; INSULIN RESISTANCE; LIVER DISEASE; MALE; METABOLITE; PNPLA3 GENE; PRIORITY JOURNAL; SINGLE NUCLEOTIDE POLYMORPHISM; STELLATE CELL; FATTY LIVER; GENETICS; HETEROZYGOTE; HOMOZYGOTE; LIPID METABOLISM; LIVER; METABOLISM; MIDDLE AGED;

AGED; ALLELES; FATTY ACIDS; FATTY LIVER; FEMALE; HETEROZYGOTE; HOMOZYGOTE; HUMANS; LIPASE; LIPID METABOLISM; LIVER; MALE; MEMBRANE PROTEINS; MIDDLE AGED; PALMITATES; POLYMORPHISM, SINGLE NUCLEOTIDE; RETINOIDS; TRIGLYCERIDES; VITAMIN A;

EID: 84951083544     PISSN: 0021972X     EISSN: 19457197     Source Type: Journal    
DOI: 10.1210/jc.2015-2978     Document Type: Article

References (23)

1. Romeo S, Kozlitina J, Xing C, Pertsemlidis A, et al. Genetic variation in PNPLA3 confers susceptibility to nonalcoholic fatty liver disease. Nat Genet. 2008;40:1461-1465.
2. Anstee QM, Day CP. The genetics of NAFLD. Nat Rev Gastroenterol Hepatol. 2013;10:645-655.
3. Maglio C, Pirazzi C, Pujia A, Valenti L, Romeo S. The PNPLA3 I148M variant and chronic liver disease: when a genetic mutation meets nutrients. Food Res Int. 2014;63:239-243.
4. Targher G, Byrne CD. A Perspective on metabolic syndrome and nonalcoholic fatty liver disease. Metab Syndr Relat Disord. 2015; 13:235-238.
5. Kantartzis K, Peter A, Machicao F, 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.
6. Basantani MK, Sitnick MT, Cai L, et al. Pnpla3/Adiponutrin deficiency in mice does not contribute to fatty liver disease or metabolic syndrome. J Lipid Res. 2011;52:318-329.
7. ChenW,Chang B, Li L, Chan L. Patatin-like phospholipase domaincontaining 3/adiponutrin deficiency in mice is not associated with fatty liver disease. Hepatology. 2010;52:1134-1142.
8. Li JZ, Huang Y, Karaman R, Ivanova PT, et al. Chronic overexpression of PNPLA3I148M in mouse liver causes hepatic steatosis. J Clin Invest. 2012;122:4130-4144.
9. Kumari M, Schoiswohl G, Chitraju C, et al. Adiponutrin functions as a nutritionally regulated lysophosphatidic acid acyltransferase. Cell Metab. 2012;15:691-702.
10. Peter A, Kovarova M, Nadalin S, et al. PNPLA3 variant I148M is associated with altered hepatic lipid composition in humans. Diabetologia. 2014;57:2103-2107.
11. Mancina RM, Matikainen N, Maglio C, et al. Paradoxical dissociation between hepatic fat content and de novo lipogenesis due to PNPLA3 sequence variant. J Clin Endocrinol Metab. 2015;100: E821-E825.
12. Pirazzi C, Valenti L, Motta BM, et al. PNPLA3 has retinyl-palmitate lipase activity inhumanhepatic stellate cells.HumMolGenet. 2014; 23:4077-4085.
13. Puche JE, Saiman Y, Friedman SL. Hepatic stellate cells and liver fibrosis. Compr Physiol. 2013;3:1473-1492.
14. Chen G. The link between hepatic vitamin A metabolism and nonalcoholic fatty liver disease. Curr Drug Targets. In press.
15. Taschler U, Schreiber R, Chitraju C, et al. Adipose triglyceride lipase is involved in the mobilization of triglyceride and retinoid stores of hepatic stellate cells. Biochim Biophys Acta. 2015;1851:937-945.
16. Peter A, Cegan A, Wagner S, et al. Hepatic lipid composition and stearoyl-coenzyme A desaturase 1 mRNA expression can be estimated from plasma VLDL fatty acid ratios. Clin Chem. 2009;55: 2113-2120.
17. Kim YK, Quadro L. Reverse-phase high-performance liquid chromatography (HPLC) analysis of retinol and retinyl esters in mouse serum and tissues. Methods Mol Biol. 2010;652:263-275.
18. Got L, Gousson T, Delacoux E. Simultaneous determination of retinyl esters and retinol in human livers by reversed-phase high-performance liquid chromatography. J Chromatogr B Biomed Appl. 1995;668:233-239.
19. Sookoian S, Pirola CJ. 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. Zhou Y, Llaurado G, Oresic M, Hyotylainen T, Orho-Melander M, Yki-Jarvinen H. Circulating triacylglycerol signatures and insulin sensitivity in NAFLD associated with the E167K variant in TM6SF2. J Hepatol. 2015;62:657-663.
21. Salameh H, Raff E, Erwin A, et al. PNPLA3 gene polymorphism is associated with predisposition to and severity of alcoholic liver disease. Am J Gastroenterol. 2015;110:846-856.
22. Blaner WS, O'Byrne SM, Wongsiriroj N, et al. Hepatic stellate cell lipid droplets: a specialized lipid droplet for retinoid storage. Biochim Biophys Acta. 2009;1791:467-473.
23. Chaves GV, Pereira SE, Saboya CJ, Spitz D, Rodrigues CS, Ramalho A. Association between liver vitamin A reserves and severity of nonalcoholic fatty liver disease in the class III obese following bariatric surgery. Obes Surg. 2014;24:219-224.