Genistein improves systemic metabolism and enhances cold resistance by promoting adipose tissue beiging

Genistein, a naturally occurring phytoestrogen and a member of the large class of compounds known as isoflavones, exerts protective effects in several diseases. Recent studies indicate that genistein plays a critical role in controlling body weight, obesity-associated insulin resistance, and metabolic disorders, but its target organs in reversing obesity and related pathological conditions remain unclear. In this study, we showed that mice supplemented with 0.2% genistein in a high-fat diet for 12 weeks showed enhanced metabolic homeostasis, including reduced obesity, improved glucose uptake and insulin sensitivity, and alleviated hepatic steatosis. We also observed a beiging phenomenon in the white adipose tissue and reversal of brown adipose tissue whitening in these mice. These changes led to enhanced resistance to cold stress. Altogether, our data suggest that the improved metabolic profile in mice treated with genistein is likely a result of enhanced adipose tissue function. •Genistein supplementation suppresses food intake and reduces body weight, leading to improved systemic metabolism.•Genistein supplementation inhibits adipocyte hypertrophy and promotes WAT beiging in diet-induced obese mice.•A diet supplemented with genistein restores BAT morphology and thermogenic gene expression in diet-induced obese mice.•Genistein supplementation contributes to higher subcutaneous temperature and better adaptation to acute cold challenges.