6-7-dihydroxyflavone and Weight-Gain

7,8-Dihydroxyflavone (DHF) is a naturally occurring flavonoid that has been reported to protect against a variety of pathologies. Chronic administration of DHF prevents high-fat diet (HFD)-induced obesity in female, but not male, mice. However, the mechanisms underlying this sexual dimorphism have not been elucidated. We have discovered that oral DHF supplementation significantly attenuates fat mass, hepatic lipid accumulation, and adipose tissue inflammation in female mice. In contrast, male mice were not protected from adiposity, and had a paradoxical worsening of hepatic lipid accumulation and adipose tissue inflammation upon DHF supplementation. Consistent with these sexually dimorphic effects on body weight and metabolic health, 7,8-DHF induced early and stable remodeling of the female intestinal microbiome. DHF supplementation significantly increased gut microbial diversity, and suppressed potentially detrimental bacteria, particularly

Topics: Adipokines; Adipose Tissue; Animals; Diet, High-Fat; Feces; Female; Flavones; Gastrointestinal Microbiome; Inflammation; Lipid Metabolism; Liver; Male; Mice; Mice, Inbred C57BL; Obesity; Sex Factors; Weight Gain

7,8-Dihydroxyflavone (7,8-DHF) is a small molecular weight compound that mimics the functions of brain-derived neurotrophic factor (BDNF). The current study aims to elucidate the molecular mechanism of 7,8-DHF-induced body weight regulation.. Obese female C57/BL6 (20-week-old) mice that have been fed with high-fat diet for 13 weeks were treated with 7,8-DHF for 9 weeks. Various biochemical and molecular analyses were performed to examine the signal transduction pathway, metabolite content, and mitochondrial mass in the animals. Moreover, systemic energy metabolism and insulin sensitivity were determined by indirect calorimetry and insulin/glucose-tolerance tests. We have also determined the metabolic actions of 7,8-DHF on cultured myotubes.. 7,8-DHF treatment increased cellular respiration by promoting mitochondrial biogenesis in cultured skeletal muscle cells. In diet-induced obese mice, subsequent 7,8-DHF consumption triggered the AMPK/CREB/PGC-1α pathways to increase the muscular mitochondrial content. Systemic energy metabolism was thus elevated, which reduced the body weight gain in obese animals. Consequently, hyperlipidemia, hyperglycemia hyperinsulinemia, and ectopic lipid accumulation in skeletal muscle and liver of the obese animals were alleviated after 7,8-DHF treatment. Moreover, insulin sensitivity of the obese muscle was improved after 7,8-DHF consumption.. 7,8-DHF treatment increases muscular mitochondrial respiration and systemic energy expenditure, which alleviates the body weight gain and partially reverse the metabolic abnormalities induced by obesity.

Topics: Adipocytes; Animals; Anti-Obesity Agents; Biomimetics; Brain-Derived Neurotrophic Factor; Diet, High-Fat; Energy Metabolism; Female; Flavones; Glucose Tolerance Test; Insulin Resistance; Mice; Mice, Inbred C57BL; Mice, Obese; Mitochondria, Muscle; Muscle, Skeletal; Obesity; Organelle Biogenesis; Signal Transduction; Weight Gain