Naringenin activates beige adipocyte browning in high fat diet-fed C57BL/6 mice by shaping the gut microbiota

Naringenin is a kind of natural citrus flavonoid with various biological and pharmacological functions. Several studies have reported the anti-obesity effect of naringenin, but its potential mechanism of action (MoA) on beige adipose browning remains unclear. Here, we investigated whether naringenin induces gut microbe-host interactions to promote beige adipose thermogenesis and browning. Naringenin treatment alleviated obesity, increased body's energy expenditure and activated inguinal white adipose tissue thermogenesis and browning in high fat diet (HFD) fed mice. In addition, naringenin improved HFD-induced gut microbiota dysbiosis and increased short-chain fatty acid (SCFA) levels (especially acetic acid) in a host's cecum and serum. Furthermore, using antibiotic treatment and gut microbe transplantation, we found that gut microbes played an indispensable role in naringenin-induced beige fat browning and naringenin-exerted anti-obesity effects. Our study suggests that naringenin activated beige adipose thermogenesis and browning by gut microbe-SCFA-host interactions, which increase energy expenditure and prevent HFD-induced obesity.