Loss Of Rab5a In Skeletal Muscle Induces Obesity And Impairs Plasma Glucose Homeostasis

Skeletal muscle is important for maintaining the body’s metabolic homeostasis When blood sugar is elevated,skeletal muscle responds to insulin stimulation to increase glucose intake and maintain blood sugar stability.As a member of the Ras-related small GTPase family,Rab5 is involved in the regulation of protein sorting,autophagy,mitochondrial homeostasis,chromatin alignment,cell migration,and energy metabolism.In this study,we applied cre/loxp system technology to create a skeletal muscle-specific knock-out Rab5a mouse line.The nine-month-old Rab5a mKO mice with normal diet showed increased body weight,white fat content,and insulin resistance.By performing blood glucose test(GTT)and insulin test(ITT)on three-month-old Rab5a mKO mice that have no obese phenotype,we found that they have a metabolic disorder such as blood glucose level imbalance and insulin resistance.These results indicate that the loss of Rab5a in mouse skeletal muscle led to the metabolic disorder and obese phenotype in mice.In addition,we found no significant difference in the expression levels of IR and IRS 1 in skeletal muscle between the control mice and the Rab5a mKO mice.In summary,our work has found that skeletal muscle Rab5a can regulate metabolism and may be a potential target for the treatment of obesity and type 2 diabetes.