SIRT3 Deficiency Promotes High‐Fat Diet‐Induced Nonalcoholic Fatty Liver Disease in Correlation with Impaired Intestinal Permeability through Gut Microbial Dysbiosis

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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