Objective This study investigated the antiobesity effects of nicotiflorin, a flavonol glycoside structurally related to rutin, by examining its ability to activate brown adipose tissue (BAT) through the β3–adrenergic receptor (β3‐AR) pathway in mice with high‐fat diet (HFD)–induced obesity. Methods Male C57BL/6 mice were fed an HFD and received daily supplementation with nicotiflorin at low (50 mg/kg) or high (100 mg/kg) doses, rutin (50 mg/kg), or the β3‐AR agonist CL316243 (0.1 mg/kg) for 8 weeks. Molecular docking simulations were conducted to predict the binding affinity of nicotiflorin to β3‐AR. The effects of nicotiflorin on body weight, food intake, blood lipid profiles, white adipose tissue (WAT) browning, BAT thermogenesis, and the expression of thermogenesis‐related genes in BAT were assessed through thermal imaging, histological analysis, and real‐time reverse transcriptase polymerase chain reaction. Results Molecular docking revealed that nicotiflorin binds strongly to β3‐AR, forming multiple hydrogen bonds with key residues. In vivo, nicotiflorin supplementation significantly reduced body weight gain, adiposity, and serum triglyceride and cholesterol levels in HFD‐fed mice, with effects comparable to those of rutin and CL316243. Crucially, nicotiflorin induced WAT browning, as evidenced by the upregulation of the expression of the Tmem26 and Uncoupling protein 1 genes. Thermal imaging revealed significant increases in the temperature of the interscapular region and the BAT/body weight ratio, indicating enhanced BAT thermogenesis. Additionally, nicotiflorin supplementation resulted in the upregulation of the expression of the genes for proteins involved in the β3‐AR, adenosine monophosphate‐activated protein kinase, peroxisome proliferator–activated receptor γ coactivator 1 α , mitochondrial biogenesis, fatty acid oxidation, and thermogenesis pathways in BAT, particularly in the high‐dose group. Conclusions Nicotiflorin effectively alleviates obesity by activating BAT through the β3‐AR pathway, promoting thermogenesis and fat oxidation. The findings suggest that nicotiflorin is a promising agent for treating obesity and metabolic disorders.
Chiu et al. (Thu,) studied this question.