ganoderic-acid-a and Obesity

Obesity is not only viewed as a chronic aggressive disorder but is also associated with an increased risk for various diseases. Nonetheless, new anti-obesity drugs are an urgent need since few pharmacological choices are available on the market. Natural compounds have served as templates for drug discovery, whereas modified molecules from the leads identified based on in vitro models often reveal noncorresponding bioactivity between in vitro and in vivo studies. Therefore, to provide inspiration for the exploration of innovative anti-obesity agents, recent discoveries of natural anti-obesity compounds with in vivo evidence have been summarized according to their chemical structures, and the comparable efficacy of these compounds is categorized using animal models. In addition, several synthetic derivatives optimized from the phytochemicals are also provided to discuss medicinal chemistry achievements guided by natural sources.

Topics: Animals; Anti-Obesity Agents; Drug Discovery; Obesity; Phytochemicals

Obesity and its major co-morbidity, type 2 diabetes, have been an alarming epidemic prevalence without an effective treatment available. Sterol regulatory element-binding proteins (SREBPs) are major transcription factors regulating the expression of genes involved in biosynthesis of cholesterol, fatty acid and triglyceride. Therefore, inhibition of SREBP pathway may be a useful strategy to treat obesity with type 2 diabetes. Here, we identify a small molecule, Ganoderic Acid A (GAA), inhibits the SREBP expression and decreases the cellular levels of cholesterol and fatty acid in vitro. GAA also ameliorates body weight gain and fat accumulation in liver or adipose tissues, and improves serum lipid levels and insulin sensitivity in high fat diet (HFD)-induced obese mice. Consistently, GAA regulates SREBPs target genes and metabolism associated genes in liver or adipose tissues, which may directly contribute to the lower lipid level and improvement of insulin resistance. Taken together, GAA could be a potential leading compound for development of drugs for the prevention of obesity and insulin resistance.

Topics: Adipose Tissue; Animals; Aspartate Aminotransferases; Body Weight; Cholesterol; Diet, High-Fat; Energy Metabolism; Glucose Tolerance Test; Hep G2 Cells; Heptanoic Acids; Humans; Insulin Resistance; Lanosterol; Lipid Metabolism; Liver; Male; Mice; Mice, Inbred C57BL; Obesity; Signal Transduction; Sterol Regulatory Element Binding Proteins; Triglycerides