Regulation of muscle physiology by 7,8-dihydroxyflavone

Abstract

Obesity is a result of imbalanced energy intake and expenditure. Since skeletal muscle is the largest contributor to overall metabolic rate, enhancing energy expenditure in this tissue is a potential method to reduce the body weight gain during energy surplus. In our attempts to identify new bioavailable compounds with anti-obesity activities, we found that 7,8-dihydroxyflavone (7,8-DHF), a naturally occurring flavone in Godmania aesculifolia, increased mitochondrial biogenesis and lipid oxidation in cultured muscle cells via the brain-derived neurotrophic factor (BDNF) receptor/ AMP-activated protein kinase (AMPK)/ peroxisome proliferator-activated receptor γ coactivator 1α (PGC-1α) pathway. In obese mice, 7,8-DHF consumption increased the muscular mitochondrial content and uncoupling protein 1 (UCP1) expression. Systemic energy metabolism was thus elevated, which reduced their body weight gain. Consequently, hyperlipidemia, hyperglycemia hyperinsulinemia, ectopic lipid accumulation, and insulin resistance in the skeletal muscle of these obese animals were alleviated after 7,8-DHF treatment. 7,8-DHF also possesses a preventive activity against obesity development as high-fat diet (HFD) feeding induced less body weight gain in C57BL/6 mice receiving 7,8-DHF simultaneously. Together, our results demonstrate that 7,8-DHF is an effective anti-obesity agent in both normal and obese animals.