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Kovarova, M.* ; Königsrainer, I.* ; Königsrainer, A.* ; Machicao, F. ; Häring, H.-U. ; Schleicher, E. ; Peter, A.

The genetic variant I148M in PNPLA3 is associated with increased hepatic retinyl-palmitate storage in humans.

J. Clin. Endocrinol. Metab. 100, E1568–E1574 (2015)
DOI PMC
Open Access Green as soon as Postprint is submitted to ZB.
CONTEXT: Previous studies revealed that the common sequence variant I148M in patatin-like phospholipase domain-containing protein 3 (PNPLA3) is associated with liver fat content and liver diseases but not with insulin resistance. Recent data suggests that the PNPLA3 I148M variant has reduced retinyl-palmitate lipase activity in hepatic stellate cells. OBJECTIVE: We hypothesized that the PNPLA3 I148M variant is associated with elevated retinyl-palmitate storage in human liver as potential link to the clinical pathology. Design/Setting and Participants: Using high pressure liquid chromatography (HPLC) we quantified the retinoid metabolites in liver tissue extracts obtained from 42 human subjects including 13 heterozygous and 6 homozygous carriers of the minor PNPLA3 I148M variant. MAIN OUTCOME MEASURE(S): Retinyl-palmitate is elevated in human livers of homozygous PNPLA3 I148M allele carriers Results: The PNPLA3 I148M variant was associated with a significant increase (1.4-fold) in liver fat. The content of retinyl-palmitate was elevated and the ratio of retinol/retinyl-palmitate was reduced in liver extracts obtained from homozygous PNPLA3 I148M minor allele carriers. In a multivariate model including liver fat content, these differences remained significant independent of liver fat content. The content of the minor retinyl-fatty acid esters was similarly increased in homozygous PNPLA3 I148M carriers. CONCLUSIONS: The increased content of hepatic retinyl-palmitate and the reduced ratio of retinol/retinyl-palmitate in PNPLA3 I148M minor allele carriers support in vitro findings of an altered retinyl-palmitate lipase activity. Our results indicate that the PNPLA3 I148M variant is relevant for the retinyl-palmitate content in human liver providing a possible link to chronic liver disease.
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Publication type Article: Journal article
Document type Scientific Article
Corresponding Author
ISSN (print) / ISBN 0021-972X
e-ISSN 1945-7197
Journal Journal of Clinical Endocrinology & Metabolism, The
Quellenangaben Volume: 100, Issue: 12, Pages: E1568–E1574 Article Number: , Supplement: ,
Publisher Endocrine Society
Publishing Place Bethesda, Md.
Non-patent literature Publications
Reviewing status Peer reviewed
Institute(s) Institute of Diabetes Research and Metabolic Diseases (IDM)