Adipose tissue is inflamed in NAFLD due to obesity but not in NAFLD due to genetic variation in PNPLA3
(2013) In Diabetologia 56(4). p.886-892- Abstract
- 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... (More)
- 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. (Less)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/3636012
- author
- Lallukka, S. ; Sevastianova, K. ; Perttila, J. ; Hakkarainen, A. ; Orho-Melander, Marju LU ; Lundbom, N. ; Olkkonen, V. M. and Yki-Jarvinen, H.
- organization
- publishing date
- 2013
- type
- Contribution to journal
- publication status
- published
- subject
- keywords
- Adipose tissue, Inflammation, NAFLD, PNPLA3 genotype
- in
- Diabetologia
- volume
- 56
- issue
- 4
- pages
- 886 - 892
- publisher
- Springer
- external identifiers
-
- wos:000316076300022
- scopus:84876469227
- pmid:23334462
- ISSN
- 1432-0428
- DOI
- 10.1007/s00125-013-2829-9
- language
- English
- LU publication?
- yes
- id
- ac5c3714-324e-4a0b-8eb3-b6542cfc71af (old id 3636012)
- date added to LUP
- 2016-04-01 10:22:53
- date last changed
- 2024-03-09 20:12:18
@article{ac5c3714-324e-4a0b-8eb3-b6542cfc71af,
abstract = {{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.}},
author = {{Lallukka, S. and Sevastianova, K. and Perttila, J. and Hakkarainen, A. and Orho-Melander, Marju and Lundbom, N. and Olkkonen, V. M. and Yki-Jarvinen, H.}},
issn = {{1432-0428}},
keywords = {{Adipose tissue; Inflammation; NAFLD; PNPLA3 genotype}},
language = {{eng}},
number = {{4}},
pages = {{886--892}},
publisher = {{Springer}},
series = {{Diabetologia}},
title = {{Adipose tissue is inflamed in NAFLD due to obesity but not in NAFLD due to genetic variation in PNPLA3}},
url = {{http://dx.doi.org/10.1007/s00125-013-2829-9}},
doi = {{10.1007/s00125-013-2829-9}},
volume = {{56}},
year = {{2013}},
}