Abstract:【Abstract】 Objective To study the changes of adipocyte differentiation in the pathogenesis of senile diabetes mellitus (ADM) or glucose intolerance and explore the pathogenesis of ADM. Methods C57BL/6J mice of 6 weeks, 20 weeks and 40 weeks age were used to simulate the youth, middle age and old age humans, respectively. The body weight, epididymal fat weight/body weight, fasting blood glucose, glucose tolerance and body temperatures after cold exposure were measured. The brown adipose Tissue (BAT) in the interscapular region of the mice and the epididymal, subcutaneous, inguinal and mesenteric adipose tissue were analyzed. Realtime RTqPCR was used to detect relative mRNA expression of glucose transporter 4 (GlUT4, it’s Slc2a4(solute carrier family 2 (facilitated glucose transporter), member 4) in mice) in liver, gastrocnemius muscle, and in epididymal, subcutaneous, inguinal and mesenteric adipose tissues. The relative mRNA expressions of Ucp1, Prdm16 and Cidea genes were detected in BAT and epididymal, subcutaneous, inguinal and mesenteric adipose tissue, and CD137 and Cytc genes were detected in the last four sites. Expression of Ucp1 in BAT of mice was detected by Western Blot. Correlation analysis was done between relative mRNA expression of Ucp1 in BAT, subcutaneous and inguinal adipose tissues and fasting blood glucose in mice. Results The body weight, epididymal fat weight/body weight and fasting blood glucose level of 40weekold mice are significantly greater or higher than those of 6weekold mice (P<005), and 40weekold mice have impaired glucose tolerance(P<005). The expression of Slc2a4 gene in all parts of adipose tissues was down regulated (P<005). The lipid droplet size of brown adipocytes increased and they fused, the gene expression of Ucp1, Prdm16 and Cidea (P<005) and the Ucp1 protein decreased. The body temperature of 40weekold mice dropped more rapidly at 4 ℃ environment (P<005). The white adipocyte size in the epididymal adipose tissue increased with age, and the differentiation of beige adipocytes in subcutaneous, inguinal and mesenteric adipose tissue decreased gradually and the expression of Ucp1, Prdm16, Cidea, CD137 and CytC decreased with age (P<005). Some indicators of 20weekold mice were also changed. The expression of Ucp1 gene in BAT, subcutaneous and inguinal adipose tissues were negatively correlated with fasting blood glucose(R2=0974;R2=08933;R2=07109). Conclusion Deterioration in morphology and function of brown adipocytes and the decrease of beige adipocyte differentiation are closely related to impaired glucose tolerance in aged mice.