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Leif Groop

Leif Groop

Principal investigator

Leif Groop

A common variant in PNPLA3, which encodes adiponutrin, is associated with liver fat content in humans

Author

  • A. Kotronen
  • L. E. Johansson
  • L. M. Johansson
  • C. Roos
  • J. Westerbacka
  • A. Hamsten
  • R. Bergholm
  • P. Arkkila
  • J. Arola
  • T. Kiviluoto
  • R. M. Fisher
  • E. Ehrenborg
  • Marju Orho-Melander
  • Martin Ridderstråle
  • Leif Groop
  • H. Yki-Jarvinen

Summary, in English

It has recently been suggested that the rs738409 G allele in PNPLA3, which encodes adiponutrin, is strongly associated with increased liver fat content in three different ethnic groups. The aims of the present study were as follows: (1) to try to replicate these findings in European individuals with quantitative measures of hepatic fat content; (2) to study whether the polymorphism influences hepatic and adipose tissue insulin sensitivity; and (3) to investigate whether PNPLA3 expression is altered in the human fatty liver. We genotyped 291 Finnish individuals in whom liver fat had been measured using proton magnetic resonance spectroscopy. Hepatic PNPLA3 expression was measured in 32 participants. Hepatic and adipose tissue insulin sensitivities were measured using a euglycaemic-hyperinsulinaemic (insulin infusion 0.3 mU kg(-1) min(-1)) clamp technique combined with infusion of [3-H-3]glucose in 109 participants. The rs738409 G allele in PNPLA3 was associated with increased quantitative measures of liver fat content (p = 0.011) and serum aspartate aminotransferase concentrations (p = 0.002) independently of age, sex and BMI. Fasting serum insulin and hepatic and adipose tissue insulin sensitivity were related to liver fat content independently of genotype status. PNPLA3 mRNA expression in the liver was positively related to obesity (r = 0.62, p < 0.0001) and to liver fat content (r = 0.58, p = 0.025) in participants who were not morbidly obese (BMI < 40 kg/m(2)). A common variant in PNPLA3 increases the risk of hepatic steatosis in humans.

Department/s

  • Genomics, Diabetes and Endocrinology
  • Diabetes - Clinical Obesity

Publishing year

2009

Language

English

Pages

1056-1060

Publication/Series

Diabetologia

Volume

52

Issue

6

Document type

Journal article

Publisher

Springer

Topic

  • Endocrinology and Diabetes

Keywords

  • Non-alcoholic fatty liver
  • disease
  • rs738409
  • Liver enzymes
  • Hepatic insulin sensitivity
  • Gene expression
  • Adiponutrin
  • Adipose tissue insulin sensitivity

Status

Published

Research group

  • Genomics, Diabetes and Endocrinology
  • Diabetes - Clinical Obesity

ISBN/ISSN/Other

  • ISSN: 1432-0428