Study On Alisol A Role In High Fat Diet-induced Obesity And Metabolic Disorders

Objectives: To assess the role of alisol A in systemic metabolic syndrome caused by obesity,and to further explore the mechanism of alisol A in this process.Introduction: With the development of social economy,the number of obese people in the world has grown rapidly.Obesity and its associated metabolic disorders such as diabetes,hepatic steatosis and chronic heart diseases affect billions of individuals.Since 1997,the World Health Organization(WHO)has listed obesity as one of the five major diseases that endanger human health.Yet there is no satisfactory drug to treat this disease.Alisol A is a main active monomer molecule isolated from the traditional Chinese medicine Rhizoma Alismatis.Rhizoma Alismatis has been proven to have anti-inflammatory,anti-cancer,hypoglycemic and other biological activities.However,there is no research focused on the role of alisol A in obesity and its related metabolism,and its underlying mechanism has not yet been elucidated.Methods: By establishing a high-fat diet-induced obese mouse model and intraperitoneal injection of alisol A,blood biochemical tests,blood glucose tests,and oral fat tolerance experiments were performed to investigate the effects of alisol A on fat metabolism and blood glucose metabolism in mice.The pathological changes of liver and fat were detected by Hematoxylin and eosin(H&E)and Oil Red O staining.The genes related to adipose synthesis and β-oxidation were detected by RT-q PCR.The activation of AMPK/ACC/SREBP-1c signaling pathway was detected by Western Blot after alisol A treatment and further verified by molecular docking studies.Results: In this study,we found that alisol A,a major active triterpene isolated from the Chinese traditional medicine Rhizoma Alismatis,could significantly attenuate high-fat-diet-induced obesity.Our biochemical detection demonstrated that alisol A remarkably decrease lipid levels,alleviate glucose metabolism disorders,insulin resistance,and damaged β-oxidation in high-fatdiet-induced obese mice.In addition,we found that alisol A reduced hepatic steatosis and improved liver function in our obese mice model.Protein expression investigation revealed that alisol A had an active effect on AMPK/ACC/SREBP-1c pathway.Such bioactivity of alisol A may result from its selective binding to the catalytic region of AMPK,as suggested by the molecular docking study.Conclusion: Taken together,alisol A could serve as a promising agent for treatment of obesity and its related metabolic diseases.