Abstract
Obesity is a worldwide epidemic metabolic disease. Gut microbiota dysbiosis and bile acids (BAs) metabolism disorder are closely related to obesity. Farnesoid X-activated receptor (FXR), served as a link between gut microbiota and BAs, is involved in maintaining metabolic homeostasis and regulating glucose and lipid metabolism. We previously reported that diammonium glycyrrhizinate (DG) could alter gut microbiota and prevent non-alcoholic fatty liver disease. However, it remains ambiguous how DG affects the gut microbiota to regulate host metabolism. In this present study, 16S rRNA Illumina NovaSeq and metabolomic analysis revealed that DG treatment suppressed microbes associated with bile-salt hydrolase (BSH) activity, which, in turn, increased the levels of taurine-conjugated BAs accompanied by inhibition of ileal FXR-FGF15 signaling. As a result, several obesity-related metabolism were improved, like lower serum glucose and insulin levels, increased insulin sensitivity, few hepatic steatosis and resistance to weight gain. Additionally, decreased level of serum lipopolysaccharide was observed, which contributed to a strengthened intestinal barrier. The effect of DG on weight loss was slightly enhanced in the antibiotics-treated obese mice. Collectively, the efficacy of DG in the treatment of obesity might depend on gut microbiota-conjugated BAs-FXR axis. Hence, it will provide a potential novel approach for the treatment of obesity.
Highlights
Obesity, mainly caused by genetic and environmental factors, is a worldwide epidemic metabolic disease characterized by excessive fat accumulation
NCDG group has similar effect to those in the HFDG group versus their control mice, but only epididymal white adipose tissues (WAT) and retroperitoneal WAT were significantly less (Figure 1D), these results suggested that the weight loss effect of diammonium glycyrrhizinate (DG) on NCD mice was mainly dependent on those two WATs
The bile acids (BAs) deconjugation process is dominated by bacteria with bile-salt hydrolase (BSH) activity, which was mainly attributed to Lactobacillus, Bifidobacterium and Clostridium (Tannock et al, 1989; Tanaka et al, 1999; Begley et al, 2006)
Summary
Mainly caused by genetic and environmental factors, is a worldwide epidemic metabolic disease characterized by excessive fat accumulation. It affects body appearance and contributes to many chronic inflammatory diseases, such as type 2 diabetes, hepatic steatosis and cardiovascular diseases (Petrick et al, 2020; Scheithauer et al, 2020; Agüera et al, 2021). It is gradually acknowledged that gut microbiota make a great effect on obesity mainly by regulating energy, acquiring nutrient and storing fat (Scarpellini et al, 2010; Zhang et al, 2010). With the progression of obesity, the composition of gut microbiota can make a change. Adiposity and glucose metabolism have been improved in the antibioticstreated obese mice (Shin et al, 2014)
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