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OBJECTIVE Obesity is becoming worldwide health threat, and it results from an imbalance between energy intake and expenditure.Brown adipose tissue represents a natural target for modulation of energy expenditure.3,3,4 ,5,7-Pentamethylquercetin (PMQ) is a natural polymethoxylated flavonoid present in seabuckthorn (Hippophae rhamnoides).Our previous results found PMQ resisted monosodium glutamate (MSG) induced obesity in mice.The present study was to further evaluate the potential of PMQ for anti-obesity treatment, and the related mechanism.METHODS The effect of PMQ on 3T3-L1 preadipocytes was investigated and anti-obesity activity of PMQ was further explored using high-fat-diet-induced (HFD) obese C57BL/6 mice.During 3T3-L1 preadipocytes were differentiated into adipocytes, PMQ 0.1-10 μmol·L-1 was treated and lipid contents were quantified, along with changes in the expression of genes and proteins associated with adipocyte differentiation and adipogenesis.RESULTS PMQ inhibited glycerol release and upregulated the consumption of glucose, but inhabited the accumulation of cellular TG.in 3T3-L1 adipocytes without effect on the proliferation of 3T3-L1 preadipocytes,.On the other hand, compared to the HFD group, HFD + PMQ group had a leaner waistline, a smaller LEE index, a lower white adipose tissue (WAT) weight, but a higher BAT weight.PMQ significantly alleviated hyperglycemia, hypertriglyceridemia, hypercholesterolemia and the size of white adipocytes in HFD mice.Experiments in 3T3-L1 adipocytes and HFD mice both showed that PMQ upregulated the expression of peroxisome proliferator-activated receptor α (PPAR-α) and γ (PPAR-γ), CCAAT/enhancer-binding protein (C/EBPα), and the insulin-sensitive glucose transporter (Glut-4).Moreover, PMQ mankedly up-regulated brown genes, such as uncoupling protein-1 (UCP-1), cell death-inducing DFF45-1ike effector A (Cidea), Bone Morphogenetic Protein 7 (BMP-7) and PR domain-containing 16 (PRDM-16).CONCLUSIONS These results suggest that PMQ exerts anti-obesity effects through browning white adipocytes.