Lipid Balance Must Be Just Right to Prevent Development of Severe Liver Damage

Overview

Journal J Clin Invest

Specialty General Medicine

Date 2022 Jun 1

PMID 35642642

Authors

Timothy F Osborne

Peter J Espenshade

Affiliations

Soon will be listed here.

Abstract

Nonalcoholic fatty liver disease (NAFLD) is a major health concern that often associates with obesity and diabetes. Fatty liver is usually a benign condition, yet a fraction of individuals progress to severe forms of liver damage, including nonalcoholic steatohepatitis (NASH) and hepatocellular carcinoma (HCC). Elevated sterol regulatory element-binding protein-driven (SREBP-driven) hepatocyte lipid synthesis is associated with NAFLD in humans and mice. In this issue of the JCI, Kawamura, Matsushita, et al. evaluated the role of SREBP-dependent lipid synthesis in the development of NAFLD, NASH, and HCC in the phosphatase and tensin homolog-knockout (PTEN-knockout) NASH model. Deletion of the gene encoding SREBP cleavage-activating protein (SCAP) from the liver resulted in decreased hepatic lipids, as expected. However, SCAP deletion accelerated progression to more severe liver damage, including NASH and HCC. This study provides a note of caution for those pursuing de novo fat biosynthesis as a therapeutic intervention in human NASH.

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