Ces3/TGH Deficiency Attenuates Steatohepatitis

Area of Science:

• Hepatology
• Metabolic Diseases
• Biochemistry

Background:

• Nonalcoholic fatty liver disease (NAFLD) is a prevalent chronic liver condition, encompassing simple steatosis to nonalcoholic steatohepatitis (NASH) with inflammation and fibrosis.
• Nonalcoholic steatohepatitis (NASH) represents a more severe form of NAFLD, characterized by liver inflammation, cell death, and fibrosis, potentially leading to cirrhosis.

Purpose of the Study:

• To investigate the role of triacylglycerol hydrolase (TGH) in the pathogenesis of NAFLD and NASH.
• To determine if TGH deficiency protects against diet-induced hepatic steatosis and NASH in mouse models.

Main Methods:

• Mice lacking triacylglycerol hydrolase (TGH) were subjected to high-fat diet (HFD)-induced hepatic steatosis.
• Tgh gene expression was ablated in two independent NASH mouse models: Pemt(-/-) mice on HFD and Ldlr(-/-) mice on a Western-type diet (WTD).

Main Results:

• TGH deficiency protected mice from HFD-induced hepatic steatosis by reducing lipogenesis, increasing fatty acid oxidation, and improving insulin sensitivity.
• In NASH models, TGH deficiency significantly reduced liver inflammation, oxidative stress, and fibrosis in Pemt(-/-) mice.
• TGH deficiency also attenuated NASH progression in Ldlr(-/-) mice fed a WTD.

Conclusions:

• Triacylglycerol hydrolase (TGH) deficiency ameliorates both simple hepatic steatosis and advanced nonalcoholic steatohepatitis (NASH).
• TGH emerges as a potential therapeutic target for mitigating the progression of NAFLD and NASH.