Anti-Obesity Effects and Underlying Mechanisms of Total Polyphenols from Cydonia oblonga Miller (Quince) in High-Fat Diet-Induced Obese Mice

Obesity is a global metabolic disease closely associated with dyslipidemia, insulin resistance, hepatic steatosis, and chronic oxidative stress. Cydonia oblonga Miller (COM, Quince) from Xinjiang Uygur Autonomous Region of China is a traditional medicinal and edible plant rich in polyphenols, flavonoids, polysaccharides, and other bioactive constituents. Our previous studies suggested that total polyphenols of Cydonia oblonga Miller (TPCOM) may exert promising anti-obesity effects. Objective: This study aimed to investigate the therapeutic effects of TPCOM on high-fat diet-induced obese C57BL/6 mice and to explore its underlying molecular mechanisms related to glycolipid metabolism. Methods: TPCOM was extracted and purified from Xinjiang Cydonia oblonga fruits, and its total polyphenol content was determined using the Folin–Ciocalteu method. C57 mice were randomly divided into normal diet, model, and TPCOM intervention groups. After 12 weeks of high-fat diet feeding and 6 weeks of TPCOM treatment, body weight was monitored continuously. Serum levels of triglyceride (TG), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), and total antioxidant capacity (T-AOC) were measured using commercial kits. Hepatic pathological changes were observed by hematoxylin–eosin (HE) staining. Bioinformatics analyses including GO and KEGG were performed to predict key targets and pathways related to lipid metabolism. The protein expression levels of PPARGC1A, FFAR1, KLF15, Adipolin, GLUT4, and phosphorylated p38 MAPK in liver tissues were detected by Western blotting. Results: TPCOM intervention significantly reduced body weight gain in obese mice in a dose-dependent manner. Serum biochemical assays showed that TPCOM decreased TC, TG, and LDL-C levels, increased HDL-C levels, and markedly enhanced total antioxidant capacity (T-AOC). Bioinformatics analysis suggested that PPARG and FFAR1 were highly expressed in liver tissue and may participate in glucose and lipid metabolism regulation. Western blot results confirmed that TPCOM significantly upregulated the expression of PPARGC1A, FFAR1, KLF15, Adipolin, GLUT4, and phosphorylated p38 MAPK in the liver of obese mice. Conclusions: TPCOM effectively ameliorates obesity, dyslipidemia, hepatic steatosis, and oxidative stress in high-fat diet-induced obese mice. The underlying mechanism may be related to the regulation of glycolipid metabolism, mitochondrial function, insulin sensitivity, and antioxidant signaling via activating the FFAR1–PPARG–p38 MAPK axis and downstream targets including PPARGC1A, KLF15, Adipolin, and GLUT4. This study provides a scientific basis and theoretical support for the development and application of TPCOM as a natural functional ingredient in the prevention and adjuvant treatment of obesity and related metabolic disorders.