The PNPLA3 Ile148Met interacts with overweight and dietary intakes on fasting triglyceride levels
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- 作者：Ivana A. Stojkovic (1)
Ulrika Ericson (1)
Gull Rukh (1)
Martin Riddestr?le (2) (3)
Stefano Romeo (4)
Marju Orho-Melander (1) (5) - 关键词：PNPLA3 ; Diet ; Fasting triglycerides ; NAFLD ; Sucrose ; Polyunsaturated fatty acids
- 刊名：Genes & Nutrition
- 出版年：2014
- 出版时间：March 2014
- 年：2014
- 卷：9
- 期：2
- 全文大小：315 KB
- 参考文献：1. Abdemalek FM, Suzuki A, Guy C, Unalp AA, Colvin R, Johnson JR, Diehl MA (2010) Increased fructose consumption is associated with fibrosis severity in patients with NAFLD. Hepatology 51(6):1961-971 CrossRef
2. Basantani MK, Sitnick MT, Cai L, Brenner DS, Gardner NP, Li JZ, Schoiswohl G, Yang K, Kumari M, Gross RW, Zechner R, Kershaw EE (2011) PNPLA3/Adiponutrin deficiency in mice does not contribute to fatty liver disease or metabolic syndrome. J Lipid Res 52:318-29 CrossRef
3. Baulande S, Lasnier F, Lucas M, Pairault J (2001) Adiponutrin, a transmembrane protein corresponding to a novel dietary and obesity linked mRNA specifically expressed in the adipose lineage. J Biol Chem 276:33336-3344 CrossRef
4. Berglund G, Elmstahl S, Janzon L, Larsson A (1993) The Malmo Diet and Cancer study. Design and feasibility. J Intern Med 233:45-1 CrossRef
5. Berglund G, Eriksson KF, Israelsson B, Kjellstrom T, Lingarde F, Mattiasson I, Nilsson JA, Stavenow L (1996) Cardiovascular risk groups and mortality in an urban swedish male population: the Malmo Preventive Project. J Intern Med 239(6):489-97 CrossRef
6. Callmer E, Riboli E, Saracci R, Akesson B, Lindgarde F (1993) Dietary assessment methods evaluated in the Malmo food study. J Intern Med 233(1):53-7 CrossRef
7. Chen W, Chang B, Li L, Chan L (2010) Patatin-like phospholipase domain containing 3/adiponutrin deficiency in mice is not associated with Fatty Liver Disease. Hepatology 52:1134-142 CrossRef
8. Cortez-Pinto H, Jesus L, Barros H, Lopes C, Moura MC, Camilo ME (2006) How different is the dietary pattern in non-alcoholic steatohepatitis patients? Clin Nutr 25:816-23 CrossRef
9. Davis JN, Le KA, Walker RW, Vikman S, Metz DS, Weigensberg JM, Allayee H, Goran MI (2010) Increased hepatic fat in overweight Hispanic youth influenced by interaction between genetic variation in PNPLA3 and high dietary carbohydrates and sugar consumption. Am J Clin Nutr 92:1522-527 CrossRef
10. Del Giudice ME, Grandone A, Cirillo G, Santoro N, Amato A, Brienza C, Savarese P, Marzuillo P, Perrone L (2011) The association of PNPLA3 variants with liver enzymes in childhood obesity is driven by the interaction with abdominal fat. PLoS ONE 6(11):e27933 CrossRef
11. Dubuquoy C, Robichon C, Lasnier F, Langlois C, Dugail I, Fabienne F, Girard J, Burnol FA, Postic C, Moldes M (2011) Distinct regulation of adiponutrin/PNPLA3 gene expression by the transcription factor ChREBP and SREBP1c in mouse and in human hepatocytes. J Hepatol 55:145-53 CrossRef
12. Goran MI, Walker R, Le KA, Mahurkar S, Vikman S, Davis JN, Metz-Spruijt D, Weigensberg MJ, Allayee H (2010) Effects of PNPLA3 on liver fat and metabolic profile in Hispanic children and adolescents. Diabetes 59:3127-130 CrossRef
13. He S, McPaul C, Li JZ, Garuti R, Kinch L, Grishin NV, Cohen JC, Hobbs HH (2010) A sequence variation (I148M) in PNPLA3 associated with nonalcoholic fatty liver disease disrupts triglyceride hydrolysis. JBC 285(9):6706-715 CrossRef
14. Hoekstra M, Li Z, Kruijt JK, Van Eck M, Van Berkel TJC, Kuiper J (2010) The expression level of non-alcoholic fatty liver disease-related gene PNPLA3 in hepatocytes is highly influenced by hepatic lipid status. J Hepatol 52:244-51 CrossRef
15. Huang Y, He S, Li JZ, Seo KY, Osborne FT, Cohen JC, Hobbs HH (2010) A feed forward loop amplifies nutritional regulation of PNPLA3. Proc Natl Acad Sci USA 107(17):7892-897 CrossRef
16. Huang Y, Cohen JC, Hobbs HH (2011) Expression and characterization of a PNPLA3 protein isoform (I148M) associated with Nonalcoholic fatty liver disease. JBC 286(43):37085-7093 CrossRef
17. Hyysalo J, Stojkovic I, Kotronen A, Hakkarainen A, Sevastinova K, Makkonen J, Lundbom N, Rissanen A, Krauss MR, Melander O, Orho-Melander M, Yki-J?rvinen H (2011) Genetic variation in PNPLA3 but not APOC3 influences liver fat in NAFLD. J Gastroenterol Hepatol 27:951-56 CrossRef
18. Johansson LE, Hoffstedt J, Parikh H, Carlsson E, Wabitsch M, Bondenson AG, Hedenbro J, Tornqvist H, Groop L, Ridderstr?le M (2006) Variation in the adiponutrin gene influences its expression and associates with obesity. Diabetes 55:826-33 CrossRef
19. Kantartzis K, Peter A, Machicao F, Machann J, Wagner S, Konigsrainer A, Schick F, Fritsche A, Haring HU, Stefan N (2009) Dissociation between fatty liver and insulin resistance in humans carrying a variant of the patatin-like phospholipase 3 gene. Diabetes 58:2616-623 CrossRef
20. Kotronen A, Johansson LE, Johansson LM, Roos C, Westerbacka J, Hamsten A, Bergholm R, Arkkila P, Arola J, Kiviluoto T, Fisher RM, Ehrenborg E, Orho-Melander M, Ridderstr?le M, Groop L, Yki-J?rvinen H (2009) A common variant in PNPLA3, which encodes adiponutrin, is associated with liver fat content in humans. Diabetologia 52:1056-060 CrossRef
21. Krarup TN, Grarup N, Banasik K, Friedrichsen M, Farch K, Sandholt HC, Jorgensen T, Poulsen P, Witte RD, Vaag A, S?rensen T, Pedersen O, Hansen T (2012) The PNPLA3 rs738409 G-allele associates with reduced fasting serum triglyceride and serum cholesterol in Danes with impaired glucose regulation. PLoS ONE 7(7):e40376 CrossRef
22. Kumari M, Schoiswohl G, Chitraju C, Paar M, Cornaciu I, Rangrez AY, Wongsiriroj N, Nagy HM, Ivanova PT, Scott SA, Knittelfelder O, Rechberger GN, Gruenberger RB, Eder S, Brown HA, Haemmerle G, Oberer M, Lass A, Kershaw EE, Zimmermann R, Zechner R (2012) Adiponutrin functions as a nutritionally regulated lysophosphatidic acid acyltransferase. Cell Metab 15:691-02 CrossRef
23. Le KA, Ith M, Kreis R, Faeh D, Bortolotti M, Tran C, Boesch C, Tappy L (2009) Fructose overconsumption causes dyslipidemia and ectopic lipid deposition in healthy subjects with and without family history of type 2 diabetes. Am J Clin Nutr 89:1760-765 CrossRef
24. Li JZ, Huang Y, Karaman R, Ivanova PT, Brown HA, Roddy T, Castro-Perez J, Cohen JC, Hobbs HH (2012) Chronic overexpression of PNPLA3I148M in mouse liver causes hepatic steatosis. J Clin Invest 122(11):4130-144 CrossRef
25. Liu YM, Moldes M, Bastard JP, Bruckert E, Viguerie N, Hainque B, Basdevant A, Langin D, Pairault J, Clement K (2004) Adiponutrin: a new gene regulated by energy balance in human adipose tissue. J Clin Endocrinol Metab 89(6):2684-689 CrossRef
26. Maersk M, Belza A, Jorgensen HS, Ringgaard S, Chabanova E, Thomsen H, Pedersen SB, Astrup A, Richelsen B (2012) Sucrose-sweetened beverages increase fat storage in the liver, muscle and visceral fat depot: a 6-mo randomized intervention study. Am J Clin Nutr 95:283-89 CrossRef
27. Manjer J, Carlsson S, Elmstahl S, Gullberg B, Janzon L, Lindstr?m M, Mattisson I, Berglund G (2001) The Malm? Diet and Cancer study: representativity, cancer incidence and mortality in participants and non-participants. Eur J Cancer Prev 10(6):489-99 CrossRef
28. Mattisson I, Wirfalt E, Aronsson CA, Wallstrom P, Berglund G (2005) Misreporting of energy: prevalence, characteristics of misreporters and influence on observed risk estimates in the Malmo Diet and Cancer cohort. Br J Nutr 94(5):832-42 CrossRef
29. Nilsson PM, Engstrom G, Hedblad B (2007) The metabolic syndrome and incidence of cardiovascular disease in non-diabetic subjects-a population-based study comparing three different definitions. Diabet Med 24(5):464-72 CrossRef
30. Nobili V, Bedogni G, Donati B, Alisi A, Valenti L (2013) The I148M variant of PNPLA3 reduces the response to docosahexaenoic acid in children with non-alcoholic fatty liver disease. J Med Food 00:1-
31. Palmer CNA, Maglio C, Pirazzi C, Burza AM, Adiels M, Burch L, Donnelly AL, Colhoun H, Doney SA, Dillon FJ, Pearson ER, McCarthy M, Hattersley AT, Frayling T, Morris AD, Peltonen M, Svensson PA, Jacobson P, Boren J, Sj?str?m L, Carlsson LMS, Romeo S (2012) Paradoxical lower serum triglyceride levels and higher type 2 diabetes mellitus susceptibility in obese individuals with the PNPLA3148M variant. PLoS ONE 7(6):e39362 CrossRef
32. Perttila J, Huaman SC, Caron S, Tanhuanpaa K, Staels B, Yki-J?rvinen H, Olkkonen MV (2012) PNPLA3 is regulated by glucose in human hepatocytes, and its I148M slows down triglyceride hydrolysis. Am J Physiol Endocrinol Metab 302:1063-069 CrossRef
33. Pignitore P, Pirazzi C, Mancina RM, Motta BM, Indiveri C, Pujia A, Montalcini T, Hedfalk K, Romeo S (2013) Recombinant PNPLA3 protein shows triglyceride hydrolase activity and its I148M mutation results in loss of function. Biochim Biophys Acta S1388-1981(13)00279-5
34. Pirazzi C, Adiels M, Burza AM, Mancina MR, Levin M, Stahlman M, Taskinen MR, Melander MO, Perman J, Pujia A, Andersson L, Maglio C, Montalcini T, Wiklund O, Borén J, Romeo S (2012) Patatin like phospholipase domain containing 3 (PNPLA3) I148M (rs738409) affects hepatic VLDL secretion in humans and in vitro. J Hepatol 57(6):1276-282 CrossRef
35. Polson AD, Thompson MP (2003) Adiponutrin mRNA expression in white adipose tissue is rapidly induced by meal-feeding a high sucrose diet. Biochem Biophys Res Commun 301:261-66 CrossRef
36. Qiao A, Liang J, Ke Y, Li C, Cui Y, Shen L, Zhang H, Cui A, Liu X, Liu C, Chen Y, Zhu Y, Guan Y, Fang F, Chang Y (2010) Mouse Patatin-Like Phospholipase Domain-Containing 3 influences systemic lipid and glucose homeostasis. Hepatology 54:509-21 CrossRef
37. Riboli E, Elmstahl S, Saracci R, Gullberg B, Lindgarde F (1997) The Malmo Food Study: validity of two dietary assessment methods for measuring nutrient intake. Int J Epidemiol 26:S161–S173 CrossRef
38. Romeo S, Kozlitina J, Xing C, Pertsemlidis A, Cox D, Pennacchio LA, Boerwinkle E, Cohen JC, Hobbs HH (2008) Genetic variation in PNPLA3 confers susceptibility to non-alcoholic fatty liver disease. Nat Genet 40:1461-465 CrossRef
39. Romeo S, Sentinelli F, Cambuli MV, Incani M, Congiu T, Matta V, Pilia S, Doran HI, Cossu E, Loche S, Baroni MG (2010a) The 148M allele of the PNPLA3 gene is associated with indices of liver damage early in life. J Hepatol 53:335-38 CrossRef
40. Romeo S, Sentinelli F, Dash S, Yeo GSH, Savage DB, Leonetti F, Capoccia D, Incani M, Maglio C, Iacovino M, O’Rahilly S, Baroni MG (2010b) Morbid obesity exposes the association between PNPLA3 I148M (rs738409) and indices of hepatic injury in individuals of European descent. Inter J Obes 34:190-94 CrossRef
41. Santoro N, Kursawe R, D’Adamo E, Dykas JD, Zhang KC, Bale EA, Cali MA, Narayan D, Shaw MM, Pierpont B, Savoye M, Lartaud D, Eldrich S, Cushman SW, Zhao H, Shulman GI, Caprio S (2010) A common variant in the patatin-like phospholipase gene (PNPLA3) is associated with fatty liver disease in obese children and adolescents. Hepatology 52:1281-290 CrossRef
42. Santoro N, Savoya M, Kim G, Marotto K, Shaw MM, Pierpont B, Caprio S (2012) Hepatic fat accumulation is modulated by the interaction between the rs738409 variant in the PNPLA3 gene and the dietary omega6/omega3 PUFA intake. PLoS ONE 7(5):e37827 CrossRef
43. Santoro N, Caprio S, Giannini C, Kim G, Kursawe R, Pierpont B, Shaw MM, Feldstein AE (2014)?Oxidized fatty acids: A potential pathogenic link between fatty liver and type 2 diabetes in obese adolescents? Antioxid Redox Signal 20(2):383-89 CrossRef
44. Sevastinova K, Santos A, Kotronen A, Hakkarainen A, Makkonen J, Silander K, Peltonen M, Romeo S, Lundbom J, Lundbom N, Olkkonen VM, Gylling H, Fielding BA, Rissanen A, Yki-J?rvinen H (2012) Effect of short term carbohydrate overfeeding and long-term weight loss on liver fat in overweight humans. Am J Clin Nutr 96:727-34 CrossRef
45. Speliotes EK, Yerges-Armstrong LM, Wu J, Hernaez R, Kim JL, Palmer CD, Gudnason V, Eiriksdottir G, Garcia ME, Launer LJ, Nalls MA, Clark JM, Mitchell BD, Shuldiner AR, Butler JL, Tomas M, Hoffmann U, Hwang SJ, Massaro JM, O’Donnell CJ, Sahani DV, Salomaa V, Schadt EE, Schwartz SM, Siscovick DS, Voight BF, Carr JJ, Feitosa MF, Harris TB, Fox CS, Smith AV, Kao WHL, Hirschhorn JN, Borecki IB (2011) Genome wide association analysis identifies variants associated with nonalcoholic fatty liver disease that have distinct effects on metabolic traits. PLoS Genet 7(3):e1001324 CrossRef
46. Valenti L, Alisi A, Galmozzi E, Bartuli A, Del Menico B, Alterio A, Dongiovanni P, Fargion S, Nobili V (2010) I148M patatin-like phospholipase domain-containing gene variant and severity of pediatric nonalcoholic fatty liver disease. Hepatology 52:1274-280 CrossRef
47. Wirfalt E, Mattisson I, Johansson U, Gullberg B, Wallstrom P, Berglund G (2001) A methodological report from the Malmo Diet and Cancer study: development and evaluation of altered routines in dietary data processing. Nutr J 1(1):3 CrossRef - 作者单位：Ivana A. Stojkovic (1)
Ulrika Ericson (1)
Gull Rukh (1)
Martin Riddestr?le (2) (3)
Stefano Romeo (4)
Marju Orho-Melander (1) (5)
1. The Clinical Nutrition Unit, Department of Clinical Sciences in Malm?, Diabetes and Cardiovascular Disease, Genetic Epidemiology, Lund University, Lund, Sweden
2. Department of Clinical Sciences, Clinical Obesity Research, Lund University, Sk?ne University Hospital Malm?, Malm?, Sweden
3. Steno Diabetes Center, Gentofte, Danmark
4. Department of Molecular and Clinical Medicine, Sahlgrenska Center for Cardiovascular and Metabolic Research, University of Gothenburg, G?teborg, Sweden
5. Clinical Research Centre, Building 91:12, SUS in Malm?, Jan Waldenstr?ms gata 35, 205 02, Malm?, Sweden - ISSN：1865-3499
文摘
The Ile148Met (rs738409, G-allele) in the patatin-like phospholipase domain-containing protein 3 gene (PNPLA3) associates with liver fat content and may lead to loss-of-function (hydrolysis) or gain-of-function (CoA-dependent lysophosphatidic acid acyltransferase) defects. PNPLA3 is up-regulated by dietary carbohydrates, and interactions between rs738409 and carbohydrates, and sugar and ω6:ω3-polyunsaturated fatty acid (PUFA) ratio on hepatic fat accumulation have been reported. We examined interaction between rs738409 and overweight, and between rs738409 and dietary intakes (carbohydrates, sucrose and ω6:ω3-PUFA ratio), on fasting triglyceride levels. From the Malmo Diet and Cancer Study-Cardiovascular Cohort, 4,827 individuals without diabetes aged 58?±?6?years, 2,346 with BMI?≤?5?kg/m2 and 2,478 with BMI?>?25?kg/m2, were included in cross-sectional analyses. Dietary data were collected by a modified diet history method. Overweight modified the association between rs738409 and fasting triglyceride levels (P interaction?=?0.003). G-allele associated with lower triglycerides only among overweight individuals (P?=?0.01). Nominally, significant interaction on triglyceride levels was observed between rs738409 and sucrose among normal-weight individuals (P interaction?=?0.03). G-allele associated with lower triglycerides among overweight individuals in the lowest tertiles of carbohydrate and ω6:ω3-PUFA ratio (P?=?0.04 and P?=?0.001) and with higher triglycerides among normal-weight individuals in the highest tertile of sucrose (P?=?0.001). We conclude that overweight and dietary sucrose may modify the association between rs738409 and fasting triglyceride levels.