Polyphenol Compound 18a Modulates UCP1-Dependent Thermogenesis to Counteract Obesity

• Published in: Biomolecules (Basel, Switzerland) Switzerland), 2024-05, Vol.14 (6), p.618
• Main Authors: Wen, Xueping, Song, Yufei, Zhang, Mei, Kang, Yiping, Chen, Dandan, Ma, Hui, Nan, Fajun, Duan, Yanan, Li, Jingya
• Format: Article
• Language: English
• Subjects: 18a; Adipocytes; Adipose tissue; Adipose Tissue, Brown - drug effects; Adipose Tissue, Brown - metabolism; Adipose tissues; Animals; Bioavailability; Body fat; Diet, High-Fat - adverse effects; Energy; Energy expenditure; Energy Metabolism - drug effects; Glucose; High fat diet; Humans; Insulin; Kinases; Male; Metabolic disorders; Mice; Mice, Inbred C57BL; Obesity; Obesity - drug therapy; Obesity - metabolism; Polyphenols; Polyphenols - pharmacology; Resveratrol; Thermogenesis; Thermogenesis - drug effects; Type 2 diabetes; UCP1; Uncoupling protein 1; Uncoupling Protein 1 - genetics; Uncoupling Protein 1 - metabolism
• ISSN: 2218-273X; 2218-273X
• DOI: 10.3390/biom14060618

Recent studies increasingly suggest that targeting brown/beige adipose tissues to enhance energy expenditure offers a novel therapeutic approach for treating metabolic diseases. Brown/beige adipocytes exhibit elevated expression of uncoupling protein 1 (UCP1), which is a thermogenic protein that efficiently converts energy into heat, particularly in response to cold stimulation. Polyphenols possess potential anti-obesity properties, but their pharmacological effects are limited by their bioavailability and distribution within tissue. This study discovered , a polyphenol compound with a favorable distribution within adipose tissues, which transcriptionally activates UCP1, thereby promoting thermogenesis and enhancing mitochondrial respiration in brown adipocytes. Furthermore, in vivo studies demonstrated that prevents high-fat-diet-induced weight gain and improves insulin sensitivity. Our research provides strong mechanistic evidence that UCP1 is a complex mediator of -induced thermogenesis, which is a critical process in obesity mitigation. Brown adipose thermogenesis is triggered by via the AMPK-PGC-1α pathway. As a result, our research highlights a thermogenic controlled polyphenol compound and clarifies its underlying mechanisms, thus offering a potential strategy for the thermogenic targeting of adipose tissue to reduce the incidence of obesity and its related metabolic problems.