2-Bromo-4'-methoxychalcone and 2-Iodo-4'-methoxychalcone Prevent Progression of Hyperglycemia and Obesity via 5'-Adenosine-Monophosphate-Activated Protein Kinase in Diet-Induced Obese Mice

• Published in: International journal of molecular sciences 2018-09, Vol.19 (9), p.2763
• Main Authors: Hsieh, Chi-Ting, Chang, Fang-Rong, Tsai, Yi-Hong, Wu, Yang-Chang, Hsieh, Tusty-Jiuan
• Format: Article
• Language: English
• Subjects: Acetyl-CoA carboxylase; Adenosine; Adenosine kinase; adipocyte; Adipocytes; Adipocytes - drug effects; Adipocytes - metabolism; AMP-Activated Protein Kinases - metabolism; Animals; Body weight; Body weight gain; CCAAT-Enhancer-Binding Proteins - metabolism; Cell Line; chalcone; Chalcones - chemistry; Chalcones - pharmacology; Diabetes; Diabetes mellitus; Diabetic neuropathy; Diabetic retinopathy; Diet, High-Fat - adverse effects; Disease Models, Animal; Disease Progression; Drugs; Enzyme Activation; flavonoid; Flavonoids; Gene expression; Glucose; Glucose - metabolism; Glucose tolerance; halogen; High fat diet; Hyperglycemia; Hyperglycemia - blood; Hyperglycemia - metabolism; Hyperglycemia - prevention & control; Hyperinsulinemia; Hypoglycemic Agents - chemistry; Hypoglycemic Agents - pharmacology; Insulin; Kinases; Lead compounds; Lipid Metabolism - drug effects; Lipids; Medicine; Metabolic disorders; Metabolites; Mice; Muscle Fibers, Skeletal - drug effects; Muscle Fibers, Skeletal - metabolism; Myotubes; Obesity; Obesity - blood; Obesity - etiology; Obesity - metabolism; Obesity - prevention & control; Pharmaceutical industry; Phosphorylation; PPAR gamma - metabolism; Protein kinase; Proteins; R&D; Research & development; Skeletal muscle
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms19092763

Obesity and diabetes are global health-threatening issues. Interestingly, the mechanism of these pathologies is quite different among individuals. The discovery and development of new categories of medicines from diverse sources are urgently needed for preventing and treating diabetes and other metabolic disorders. Previously, we reported that chalcones are important for preventing biological disorders, such as diabetes. In this study, we demonstrate that the synthetic halogen-containing chalcone derivatives 2-bromo-4'-methoxychalcone (compound ) and 2-iodo-4'-methoxychalcone (compound ) can promote glucose consumption and inhibit cellular lipid accumulation via 5'-adenosine-monophosphate-activated protein kinase (AMPK) activation and acetyl-CoA carboxylase 1 (ACC) phosphorylation in 3T3-L1 adipocytes and C2C12 skeletal myotubes. In addition, the two compounds significantly prevented body weight gain and impaired glucose tolerance, hyperinsulinemia, and insulin resistance, which collectively help to delay the progression of hyperglycemia in high-fat-diet-induced obese C57BL/6 mice. These findings indicate that 2-bromo-4'-methoxychalcone and 2-iodo-4'-methoxychalcone could act as AMPK activators, and may serve as lead compounds for a new class of medicines that target obesity and diabetes.