Function of PNPLA3 I148M—Lessons From In Vivo Studies in Humans

IF 6 2区医学 Q1 GASTROENTEROLOGY & HEPATOLOGY Liver International Pub Date : 2025-03-07 DOI:10.1111/liv.70047

Hannele Yki-Järvinen, Panu K. Luukkonen

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Abstract

Background and Aims

Steatotic liver disease (SLD) associated with insulin resistance (IR) and the metabolic syndrome (‘IR-SLD’) increases the risk of liver disease, type 2 diabetes and cardiovascular disease (CVD). SLD associated with the PNPLA3 I148M variant (‘PNPLA3-SLD’) also predisposes individuals to liver disease but protects against type 2 diabetes and CVD. Although in real life the two causes of SLD commonly co-exist, the opposite effects of ‘IR-SLD’ and ‘PNPLA3-SLD’ on CVD and liver disease suggest their pathogenesis differs.

Methods and Results

This review summarises human data comparing the effects of ‘IR-SLD’ and ‘PNPLA3-SLD’ on the human liver lipidome, hepatic handling of fatty acids, pathways of intrahepatocellular triglyceride synthesis, circulating lipids and lipoproteins and adipose tissue inflammation. We also discuss how steatosis in PNPLA3 I148M carriers leads to defects in mitochondrial function.

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来源期刊

Liver International 医学-胃肠肝病学

CiteScore

13.90

自引率

4.50%

发文量

348

审稿时长

2 months

期刊介绍： Liver International promotes all aspects of the science of hepatology from basic research to applied clinical studies. Providing an international forum for the publication of high-quality original research in hepatology, it is an essential resource for everyone working on normal and abnormal structure and function in the liver and its constituent cells, including clinicians and basic scientists involved in the multi-disciplinary field of hepatology. The journal welcomes articles from all fields of hepatology, which may be published as original articles, brief definitive reports, reviews, mini-reviews, images in hepatology and letters to the Editor.