Research On The Role Of Autophagy Core Protein ATG101 In Adipose Tissue

OBJECTIVE-ATG101(Autophagy-related gene 101)is an autophagy core protein,which can form ULK1 autophagy initiation complex with ULK1-ATG13-FIP200,and plays a vital role in the process of autophagy initiation.PPARγ agonist rosiglitazone promotes adipocyte differentiation and function.Previous work found that ATG101 is the only autophagy gene that can be continuously up-regulated by rosiglitazone,this study aimed to explore the expression and function of ATG101 in adipocytes and tissues with different metabolic states.METHODS-Evaluate the effect of rosiglitazone on adipocyte autophagy and the role of ATG101 in it;Detecte ATG101 expression during differentiation of 3T3-L1 cells and mouse adipose tissue vascular stromal cells into adipocytes;Use sh RNA to knock down ATG101 in preadipocytes to observe its effect on adipocyte differentiation,function and autophagy;Detect the expression of ATG101 in subcutaneous fat tissues of normal and obese patients;Investigate the relationship between the expression of subcutaneous adipose tissue ATG101 and postoperative adipose tissue remodeling in 86 patients undergoing bariatric surgery.RESULTS-1)ATG101 knockdown caused impaired autophagy activity of white adipocytes,and rosiglitazone promoted autophagic clearance of adipocytes.2)Knockdown of ATG101 leads to distinctly decrease in the expression of the signature genes of mature adipocytes,impaired lipid droplet production,and a significant reduction in the expression of genes related to thermogenesis in beige adipocytes.3)Population studies have shown that the expression of ATG101 m RNA in subcutaneous fat tissue is positively correlated with BMI,and is also positively correlated with the expression of Leptin,CD36 and Fabp4(all P <0.01);Patients with high basal expression of ATG101 had more significant weight loss and visceral adipose tissue transfer after bariatric surgery.CONCLUSIONS-ATG101 is essential for white adipocyte autophagy and differentiation,and can promote the differentiation and thermogenesis of beige adipocytes;the expression of ATG101 in subcutaneous adipose tissue of obese patients is significantly increased,and the basic expression of ATG101 is closely related to weight loss and adipose tissue redistribution after bariatric surgery,however,the underlying mechanism still remains unclear.