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Peter, A. ; Kovarova, M.* ; Nadalin, S.* ; Cermak, T.* ; Königsrainer, A.* ; Machicao, F. ; Stefan, N. ; Häring, H.-U. ; Schleicher, E.

PNPLA3 variant I148M is associated with altered hepatic lipid composition in humans.

Diabetologia 57, 2103-2107 (2014)
DOI PMC
Open Access Green as soon as Postprint is submitted to ZB.
AIMS/HYPOTHESIS: The common sequence variant I148M of the patatin-like phospholipase domain-containing protein 3 gene (PNPLA3) is associated with increased hepatic triacylglycerol (TAG) content, but not with insulin resistance, in humans. The PNPLA3 (I148M) variant was previously reported to alter the specificity of the encoded enzyme and subsequently affect lipid composition. METHODS: We analysed the fatty acid composition of five lipid fractions from liver tissue samples from 52 individuals, including 19 carriers of the minor PNPLA3 (I148M) variant. RESULTS: PNPLA3 (I148M) was associated with a strong increase (1.75-fold) in liver TAGs, but with no change in other lipid fractions. PNPLA3 (I148M) minor allele carriers had an increased n-3 polyunsaturated fatty acid (PUFA) α-linolenic acid content and reductions in several n-6 PUFAs in the liver TAG fraction. Furthermore, there was a strong inverse correlation between n-6 PUFA and TAG content independent of PNPLA3 genotype. In a multivariate model including liver fat content, PNPLA3 genotype and fatty acid composition, two significant differences could be exclusively attributed to the PNPLA3 (I148M) minor allele: reduced stearic acid and increased α-linolenic acid content in the hepatic TAG fraction. CONCLUSIONS: These changes therefore suggest a mechanism to explain the PNPLA3 (I148M)-dependent increase in liver fat content without causing insulin resistance. Stearic acid can induce insulin resistance, whereas α-linolenic acid may protect against it.
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Publication type Article: Journal article
Document type Scientific Article
Corresponding Author
Keywords Diabetes Mellitus ; Fatty Acids ; Fatty Liver ; Hepatic Lipid Fractions ; Insulin Resistance ; Alpha-linolenic Acid ; Nafl ; Obesity ; Pnpla3(i148m) Gene Variant ; Pufa ; Triacylglycerol; Fatty Liver-disease; Confers
ISSN (print) / ISBN 0012-186X
e-ISSN 1432-0428
Journal Diabetologia
Quellenangaben Volume: 57, Issue: 10, Pages: 2103-2107 Article Number: , Supplement: ,
Publisher Springer
Publishing Place Berlin ; Heidelberg [u.a.]
Non-patent literature Publications
Reviewing status Peer reviewed
Institute(s) Institute of Diabetes Research and Metabolic Diseases (IDM)
German Center for Diabetes Reseach (DZD)