Cerasus humilis cherry polyphenol reduces high-fat diet-induced obesity in C57BL/6 mice by mitigating fat deposition, inflammation, and oxidation.

This study aimed to determine the anti-obesity effects and mechanisms of Cerasus humilis polyphenol (CHP) in C57BL/6 obese mice and 3T3-L1 cells. HPLC-ESI-MS/MS was used for the qualitative and quantitative identification of CHP components. The obese mice, induced by feeding a high-fat diet (HFD), were treated with CHP (250 mg/kg/day) by gavage for 12 weeks. Orlistat was gavaged at 15.6 mg/kg bw/day, as a positive control group. The analysis revealed that the main components of CHP were procyanidin B2, cyanidin-3-glucoside, and pelargonidin-3-glucoside. CHP dietary supplementation significantly reduced body weight and improved blood lipid measurements in HFD-fed mice (p<0.01). Moreover, it inhibited mRNA expression of miR-122, Srebp-1c, and Cpt1a (p<0.01), and reduced hepatic lipid deposition, as seen by H&E staining. CHP downregulated the protein expression of PPARγ and C/EBPα in HFD-induced obese mice and inhibited adipocyte differentiation (p<0.01). Compared with the HFD group, CHP supplementation had an obvious anti-inflammatory effect (decreased protein expression, such as TNF-α, IL-6, MCP1), reducing leptin levels, as well as TNF-α secretion in serum and cells (p<0.01). CHP significantly inhibited the expression of miR-27a/b (53.3%, 29.9%, p<0.01) in mice retroperitoneal white adipocytes, enhancing the expression of target gene Prdm16, and significantly upregulating Sirt1 (105.5%, p<0.01) compared with the HFD group. Moreover, CHP supplementation effectively improved oxidative stress (ROS, T-AOC, SOD, CAT, and GSH-Px) induced by HFD in obese mice (p<0.01). Thus, CHP mitigates adipocyte differentiation, browning of white adipocytes, and reduction of inflammation and antioxidant activity to reduce obesity. Consequently, these results provide novel insights into the anti-obesity roles of CHP in HFD-induced obesity.