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Frankó, A. ; Merkel, D.* ; Kovarova, M. ; Hoene, M.* ; Jaghutriz, B.A. ; Heni, M. ; Koenigsrainer, A.* ; Papan, C.* ; Lehr, S. ; Häring, H.-U. ; Peter, A.

Dissociation of fatty liver and insulin resistance in I148M PNPLA3 carriers: Differences in diacylglycerol (DAG) FA18:1 lipid species as a possible explanation.

Nutrients 10:1314 (2018)
Publ. Version/Full Text Research data DOI PMC
Open Access Gold
Creative Commons Lizenzvertrag
Fatty liver is tightly associated with insulin resistance and the development of type 2 diabetes. I148M variant in patatin-like phospholipase domain-containing protein 3 (PNPLA3) gene is associated with high liver fat but normal insulin sensitivity. The underlying mechanism of the disassociation between high liver fat but normal insulin sensitivity remains obscure. We investigated the effect of I148M variant on hepatic lipidome of subjects with or without fatty liver, using the Lipidyzer method. Liver samples of four groups of subjects consisting of normal liver fat with wild-type PNPLA3 allele (group 1); normal liver fat with variant PNPLA3 allele (group 2); high liver fat with wild-type PNPLA3 allele (group 3); high liver fat with variant PNPLA3 allele (group 4); were analyzed. When high liver fat to normal liver fat groups were compared, wild-type carriers (group 3 vs. group 1) showed similar lipid changes compared to I148M PNPLA3 carriers (group 4 vs. group 2). On the other hand, in wild-type carriers, increased liver fat significantly elevated the proportion of specific DAGs (diacylglycerols), mostly DAG (FA18:1) which, however, remained unchanged in I148M PNPLA3 carriers. Since DAG (FA18:1) has been implicated in hepatic insulin resistance, the unaltered proportion of DAG (FA18:1) in I148M PNPLA3 carriers with fatty liver may explain the normal insulin sensitivity in these subjects.
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Publication type Article: Journal article
Document type Scientific Article
Corresponding Author
Keywords Nafld ; Liver ; Pnpla3 ; Diacylglycerol ; Lipidomics; Hepatic Steatosis; Genetic-variation; Skeletal-muscle; Disease; Humans; Obesity; Mice; Translocation; Spectrometry; Sensitivity
ISSN (print) / ISBN 2072-6643
e-ISSN 2072-6643
Journal Nutrients
Quellenangaben Volume: 10, Issue: 9, Pages: , Article Number: 1314 Supplement: ,
Publisher MDPI
Publishing Place Basel
Non-patent literature Publications
Reviewing status Peer reviewed
Institute(s) Institute of Diabetes Research and Metabolic Diseases (IDM)