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Photo: KG Pressfoto

Marju Orho-Melander

Professor

Photo: KG Pressfoto

Adipose tissue is inflamed in NAFLD due to obesity but not in NAFLD due to genetic variation in PNPLA3

Author

  • S. Lallukka
  • K. Sevastianova
  • J. Perttila
  • A. Hakkarainen
  • Marju Orho-Melander
  • N. Lundbom
  • V. M. Olkkonen
  • H. Yki-Jarvinen

Summary, in English

The rs738409 C > G single-nucleotide polymorphism in PNPLA3 leads to a missense mutation (I148M) which increases liver fat but does not cause insulin resistance. We hypothesised that patients with non-alcoholic fatty liver disease (NAFLD) due to the PNPLA3 variant ('PNPLA3 NAFLD'aEuro parts per thousand= PNPLA3-148MM) do not have adipose tissue (AT) inflammation in contrast with those with NAFLD due to obesity ('obese NAFLD'). Biopsy specimens of AT were taken, and PNPLA3 genotype and liver fat (H-1-magnetic resonance spectroscopy) were determined in 82 volunteers, who were divided into groups based on either median BMI (obese 36.2 +/- 0.7 kg/m(2); non-obese 26.0 +/- 0.4 kg/m(2)) or PNPLA3 genotype. All groups were similar with respect to age and sex. The PNPLA3 subgroups were equally obese (PNPLA3-148MM, 31.1 +/- 1.3 kg/m(2); PNPLA3-148II, 31.2 +/- 0.8 kg/m(2)), while the obese and non-obese subgroups had similar PNPLA3 genotype distribution. Gene expression of proinflammatory (MCP-1, CD68) and anti-inflammatory (Twist1, ADIPOQ) markers was measured using quantitative real-time RT-PCR. Liver fat was similarly increased in obese NAFLD (9.5 +/- 1.3% vs 5.1 +/- 0.9%, obese vs non-obese, p = 0.007) and PNPLA3 NAFLD (11.4 +/- 1.7% vs 5.3 +/- 0.8%, PNPLA3-148MM vs PNPLA3-148II, p < 0.001). Fasting serum insulin was higher in the obese than the non-obese group (76 +/- 6 vs 47 +/- 6 pmol/l, p < 0.001), but similar in PNPLA3-148MM and PNPLA3-148II (60 +/- 8 vs 62 +/- 5 pmol/l, NS). In obese vs non-obese, MCP-1 and CD68 mRNAs were upregulated, whereas those of Twist1 and ADIPOQ were significantly downregulated. AT gene expression of MCP-1, CD68, Twist1 and ADIPOQ was similar in PNPLA3-148MM and PNPLA3-148II groups. PNPLA3 NAFLD is characterised by an increase in liver fat but no insulin resistance or AT inflammation, while obese NAFLD has all three of these features.

Department/s

  • Genomics, Diabetes and Endocrinology
  • EXODIAB: Excellence of Diabetes Research in Sweden
  • EpiHealth: Epidemiology for Health

Publishing year

2013

Language

English

Pages

886-892

Publication/Series

Diabetologia

Volume

56

Issue

4

Document type

Journal article

Publisher

Springer

Topic

  • Endocrinology and Diabetes

Keywords

  • Adipose tissue
  • Inflammation
  • NAFLD
  • PNPLA3 genotype

Status

Published

Research group

  • Genomics, Diabetes and Endocrinology

ISBN/ISSN/Other

  • ISSN: 1432-0428