The Role of Pkd in Adipocyte Differentiation, Hypertrophy, and Obesity

Obesity has been linked to many chronic diseases, such as insulin resistance, type 2 diabetes mellitus, cardiovascular diseases, and cancer. Therefore, it has become a major health issue in westernized countries including Taiwan. Obesity is primarily due to hypertrophy and de novo differentiation of adipocytes in adipose tissue. Moreover, adipocyte functions are dys-regulated in obesity. Therefore, it is important to understand how adipocytes are regulated. Recent genome-wide association studies (GWAS) have identified that PRKD1 gene to be associated with body mass index (BMI). PRKD1 gene encodes protein kinase D1 (PKD1), a member of calmodulin-dependent protein kinase (CaMK) serine/threonine kinase family, regulates many cellular and physiological functions. However, the role of PKD1 in adipocytes, the cells responsible for changes of BMI, remains largely unknown. PKD activity and protein levels in adipose tissue are differentially modulated in the progression of diet-induced obesity, suggesting that adipose PKD may play a role in obesity-associated dysregulation. Using 3T3-L1 adipocytes to elucidate cellular and molecular mechanisms, we found that PKD may regulate leptin production, glucose uptake, lipid storage, and adipocyte differentiation. Given that leptin production, lipid storage, and adipocyte differentiation are associated with obesity, we aim to use both in vivo mouse model and 3T3-L1 preadipocytes and differentiated adipocytes to address the following important questions: (1) in mice, how does diet-induced obesity modulate PKD level and functions in adipose tissue? Does weight loss reverse obesity-induced PKD dysregulation? Does modulation of PKD lead to weight change? (2) in the cell model, how does PKD modulate leptin production, lipid storage, and adipocyte differentiation? These studies not only will give us insight on the molecular mechanism controlling adipocyte functions, but also provide potential therapeutic target in treating diseases in the future.

Project ID:PC10708-0981
External Project ID:MOST107-2320-B182-041