Lipid balance must be just right to prevent development of severe liver damage

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 carc...

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Published in:The Journal of clinical investigation 2022-06, Vol.132 (11), p.1-3
Main Authors: Osborne, Timothy F, Espenshade, Peter J
Format: Article
Language:English
Subjects:
Animals
Autophagy
Biomedical research
Biosynthesis
Carcinoma, Hepatocellular - genetics
Carcinoma, Hepatocellular - pathology
Care and treatment
Cholesterol
Development and progression
Diabetes
Diabetes mellitus
Enzymes
Fatty acids
Fatty liver
Gene deletion
Genes
Health aspects
Hepatocellular carcinoma
Homeostasis
Inflammation
Lipid metabolism
Lipids
Liver cancer
Liver diseases
Liver Neoplasms - genetics
Liver Neoplasms - pathology
Mice
Non-alcoholic Fatty Liver Disease - genetics
Non-alcoholic Fatty Liver Disease - metabolism
Phosphatase
Proteins
PTEN protein
Sterol Regulatory Element Binding Protein 1
Sterol regulatory element-binding protein
Sterols
Synthesis
Tensin
Tumors
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Summary: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.
ISSN:1558-8238
0021-9738
1558-8238
DOI:10.1172/JCI160326