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Genetic variation in PNPLA3 (adiponutrin) confers sensitivity to weight loss-induced decrease in liver fat in humans

In English

Författare

  • Ksenia Sevastianova
  • Anna Kotronen
  • Amalia Gastaldelli
  • Julia Perttila
  • Antti Hakkarainen
  • Jesper Lundbom
  • Laura Suojanen
  • Marju Orho-Melander
  • Nina Lundbom
  • Eleuterio Ferrannini
  • Aila Rissanen
  • Vesa M. Olkkonen
  • Hannele Yki-Jarvinen
Visa allt

Summary, in English

Background: The rs738409 C -> G single nucleotide polymorphism in the patatin-like phospholipase domain-containing 3 (PNPLA3; adiponutrin) leads to a missense mutation (I148M), which is associated with increased liver fat but not insulin resistance. The I148M mutation impedes triglyceride hydrolysis in vitro, and its carriers have an increased risk of developing severe liver disease. Objective: We explored whether the rs738409 PNPLA3 G allele influences the ability of weight loss to decrease liver fat or change insulin sensitivity. Design: We recruited 8 subjects who were homozygous for the rs738409 PNPLA3 G allele (PNPLA3-148MM) and 10 who were homozygous for the rs738409 PNPLA3 C allele (PNPLA3-148II). To allow comparison of changes in liver fat, the groups were matched with respect to baseline age, sex, body mass index, and liver fat. The subjects were placed on a hypocaloric low-carbohydrate diet for 6 d. Liver fat content (proton magnetic resonance spectroscopy), whole-body insulin sensitivity of glucose metabolism (euglycemic clamp technique), and lipolysis ([H-2(5)] glycerol infusion) were measured before and after the diet. Results: At baseline, fasting serum insulin and C-peptide concentrations were significantly lower in the PNPLA3-148MM group than in the PNPLA3-148II group, as predicted by study design. Weight loss was not significantly different between groups (PNPLA3-148MM: -3.1 +/- 0.5 kg; PNPLA3-148II: -3.1 +/- 0.4 kg). Liver fat decreased by 45% in the PNPLA3-148MM group (P < 0.001) and by 18% in the PNPLA3-148II group (P < 0.01). Conclusion: Weight loss is effective in decreasing liver fat in subjects who are homozygous for the rs738409 PNPLA3 G or C allele. This trial was registered at www.hus.fi as 233775. Am J Clin Nutr 2011;94:104-11.

Publiceringsår

2011

Språk

Engelska

Sidor

104-111

Publikation/Tidskrift/Serie

American Journal of Clinical Nutrition

Volym

94

Issue

1

Dokumenttyp

Artikel i tidskrift

Förlag

Oxford University Press

Ämne

  • Nutrition and Dietetics

Status

Published

Forskningsgrupp

  • Diabetes - Cardiovascular Disease

ISBN/ISSN/Övrigt

  • ISSN: 1938-3207