Ketone body 3-hydroxybutyrate alleviates CCl4-induced liver fibrosis in mice through regulation of mitochondrial fission and reduction of oxidative stress

Abstract

3-Hydroxybutyrate (3HB) is an important metabolite and regulatory molecule produced in liver. Previous studies have shown that 3HB could be beneficial to many diseases, including brain diseases, diabetes, and most importantly, inflammation and liver related injury. Therefore, the effect of 3HB on liver fibrosis, one key step of liver diseases which proved to be reversible, is urgent to explore. In this study, the CCl4-induced mouse model of liver fibrosis has been successfully constructed and treated by 3HB. The results demonstrate that 3HB could alleviate CCl4-induced liver injury and inflammation in mice, decrease the accumulation of collagen, the expression of pro-fibrotic genes as well as inflammatory factors, and finally the degree of liver fibrosis. The transcriptome data recovers that the anti-fibrotic effect of 3HB might be exerted through several ways, such as regulating mitochondrial function, reducing oxidative stress and p53 signaling pathways, proposing a safe and relatively fast possibility for the treatment of liver fibrosis.