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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 möglich sobald Postprint bei der ZB eingereicht worden ist.
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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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Schlagwörter 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
Sprache englisch
Veröffentlichungsjahr 2014
HGF-Berichtsjahr 2014
ISSN (print) / ISBN 0012-186X
e-ISSN 1432-0428
Zeitschrift Diabetologia
Quellenangaben Band: 57, Heft: 10, Seiten: 2103-2107 Artikelnummer: , Supplement: ,
Verlag Springer
Verlagsort Berlin ; Heidelberg [u.a.]
Begutachtungsstatus Peer reviewed
Institut(e) Institute of Diabetes Research and Metabolic Diseases (IDM)
German Center for Diabetes Reseach (DZD)
POF Topic(s) 90000 - German Center for Diabetes Research
Forschungsfeld(er) Helmholtz Diabetes Center
PSP-Element(e) G-502400-001
G-502400-002
PubMed ID 24972532
DOI 10.1007/s00125-014-3310-0
WOS ID WOS:000341708900012
Erfassungsdatum 2014-07-16
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