Naringin ameliorates obesity via stimulating adipose thermogenesis and browning, and modulating gut microbiota in diet-induced obese mice

Naringin, a natural flavanone primarily found in citrus fruits, has garnered increased attention due to its recognized antioxidative, anti-inflammatory, and cardioprotective attributes. However, the functions of naringin in regulating energy expenditure are poorly understood. In the present study, we observed that twelve weeks of naringin supplementation substantially reshaped the metabolic profile of high-fat diet (HFD)-fed mice, by inhibiting body weight gain, reducing liver weight, and altering body compositions. Notably, naringin exhibited a remarkable capacity to augment whole-body energy expenditure of the tested mice by enhancing the thermogenic activity of brown adipose tissue (BAT) and stimulating browning of inguinal white adipose tissue (iWAT). Furthermore, our resulted showed naringin supplementation modified gut microbiota composition, specifically increased the abundance of Bifidobacterium and Lachnospiraceae_bacterium_28-4, reduced the abundance of Lachnospiraceae_bacterium_DW59 and Dubosiella_newyorkensis. Subsequently, we also found naringin supplementation altered fecal metabolite profile, by significantly promoting the production of taurine, tyrosol, and thymol, which act as potent activators of thermoregulation. Interestingly, the metabolic effects of naringin were abolished upon gut microbiota depletion through antibiotic intervention, concurrently showing the disappearance of naringin-induced thermogenesis and protective actions on diet-induced obesity. This revealed a novel food-driven cross-sectional communication between gut bacteria/adipose tissues. Collectively, our data showed naringin supplementation stimulated BAT thermogenesis, altered fat distribution, promoted the browning process, and consequently inhibited body weight gain; importantly these metabolic effects required the participation of gut bacteria.