Amphotericin B ameliorates obesity through modulating gut mycobiome dysbiosis and brown adipose tissue thermogenesis in high-fat diet-induced mice.

OBJECTIVES

The gut mycobiome influences adipose tissue thermogenesis and obesity. Amphotericin B (AmB) has been shown to improve steatohepatitis in mice fed a high-fat diet (HFD). The objective of this study was to examine the effects of AmB on diet-induced obesity and the resulting gut mycobiome dysbiosis in mice.

METHODS

Male C57BL/6 mice were fed a normal-fat diet or an HFD, with HFD-mice receiving either no treatment or AmB gavage. After 11 weeks, adipose indexes, lipid levels, tissue histology, gene expression, and the gut mycobiome composition were analysed. Key fungal species in lipid metabolism were isolated from mouse caecal contents by culture, and their cholesterol-lowering potential was assessed in vitro.

RESULTS

AmB treatment of HFD-mice decreased body weight and epididymal fat mass, increased the brown fat index, improved serum cholesterol profiles, and decreased adipocyte size. It upregulated the thermogenic genes peroxisome proliferator-activated receptor γ (PPARγ), peroxisome proliferator-activated receptor gamma coactivator 1α (PGC1α), and uncoupling protein 1 (UCP1) in adipose tissue, improved colon barrier integrity (elevated the levels of Occludin and Muc2), and altered the gut mycobiome composition by increasing the abundance of Rhodotorula and decreasing that of Aspergillus. Rhodotorula was identified as a keystone taxon. An isolated strain, R. mucilaginosa DM2025, demonstrated cholesterol-lowering capacity in vitro.

CONCLUSIONS

AmB ameliorates HFD-induced obesity by improving lipid metabolism, promoting adipose tissue browning and thermogenesis, and modulating the gut mycobiome. R. mucilaginosa may be a keystone species in the regulation of obesity.