Lack of SIRT3 may worsen fatty liver from a high-fat diet by harming gut barrier and gut bacteria

SIRT3 deficiency is associated with exacerbated hepatic steatosis and inflammation in mice on a high-fat diet.

• High-fat diet treatment for 18 weeks significantly increased liver fat and inflammation in SIRT3 knockout mice compared to wild-type mice.
• The absence of SIRT3 led to gut microbial imbalance, with notable increases in specific bacteria such as Desulfovibrio and Oscillibacter, and a decrease in Alloprevotella.
• SIRT3 knockout mice exhibited impaired intestinal barrier function and increased inflammation when fed a high-fat diet.
• Elevated levels of lipopolysaccharide were detected in the circulation of SIRT3 knockout mice on a high-fat diet, indicating compromised gut integrity.
• Dysregulated levels of cannabinoid receptors 1 and 2 in the colon and liver were observed in SIRT3KO mice, which correlated with gut microbiota changes.

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