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Itaconic acid underpins hepatocyte lipid metabolism in non-alcoholic fatty liver disease in male mice

Medicine and Health

Itaconic acid underpins hepatocyte lipid metabolism in non-alcoholic fatty liver disease in male mice

J. M. Weiss, E. M. Palmieri, et al.

Discover the groundbreaking research by Jonathan M. Weiss and colleagues, which unveils the role of itaconic acid in mitigating lipid accumulation in liver diseases. This study investigates how macrophage-derived itaconate can potentially reverse adverse metabolic conditions in non-alcoholic fatty liver disease.

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Playback language: English
Abstract
Itaconic acid, a metabolite produced during macrophage activation, is upregulated in human non-alcoholic steatohepatitis (NASH) and a mouse model of non-alcoholic fatty liver disease (NAFLD). Male mice deficient in *Irg1* (the gene responsible for itaconate production) exhibited exacerbated lipid accumulation in the liver, glucose and insulin intolerance, and mesenteric fat deposition. Treatment with 4-octyl itaconate reversed dyslipidemia. Mechanistically, itaconate reduced lipid accumulation and increased oxidative phosphorylation in hepatocytes, suggesting macrophage-derived itaconate modulates hepatic fatty acid metabolism.
Publisher
Nature Metabolism
Published On
Jun 12, 2023
Authors
Jonathan M. Weiss, Erika M. Palmieri, Marieli Gonzalez-Cotto, Ian A. Bettencourt, Emily L. Megill, Nathaniel W. Snyder, Daniel W. McVicar
Tags
Itaconic acid
Macrophage activation
Non-alcoholic steatohepatitis
Lipid accumulation
Glucose intolerance
Hepatic metabolism
Dyslipidemia

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