TY - JOUR T1 - Role of SHIP2 in Oleate Induced De-Novo Lipogenesis TT - نقش ژن SHIP2 در لیپوژنز القایی توسط اولئات JF - ajaums-jps JO - ajaums-jps VL - 10 IS - 2 UR - http://jps.ajaums.ac.ir/article-1-54-en.html Y1 - 2015 SP - 26 EP - 34 KW - De-novo lipogenesis KW - Oleate KW - SH2 domain-containing inositol 5-phosphatase (SHIP2) and Insulin resistance N2 - Introduction: Dyslipidemia is one of the key risk factors for cardiovascular disease in type 2 diabetes (T2D). The dyslipidemia is characterized by increased plasma concentration of triglycerides (TG), reduced concentration of high density lipoprotein cholesterol (HDL-C) and an increased concentration of small dense low density lipoprotein (LDL) cholesterol. Evidence from both animal and human studies suggests that insulin resistance (in adipose and liver tissues) is an important underlying cause of hypertriglyceridemia in subjects with metabolic syndrome and T2D. Hepatic de-novo lipogenesis and production of triglyceride rich VLDL are regulated via the phosphoinositide 3-kinase cascade. However, the role of a negative regulator of this pathway, the SH2 domain containing inositol 5-phosphatase (SHIP2) remains unknown. Methods and Materials: In the present study, we studied the molecular mechanisms linking SHIP2 expression to metabolic dyslipidemia using overexpression or suppression of SHIP2 gene in HepG2 cells exposed to oleate (0.5 mM). Results: The results showed that, comparing to the control group, the overexpression of the wild type SHIP2 gene (SHIP2 WT) led to a higher total lipid content (28%), whereas overexpression of the dominant negative SHIP2 gene (SHIP2-DN) reduced total lipid content in oleate treated cells by 40%. Overexpression of SHIP2-WT also lead to a significant increase in increased intra and extracellular triglyceride levels and enhanced the expression of lipogenic genes such as SREBP1c, FAS and ACC. On the other hand, overexpression of the SHIP2-DN gene prevented oleate-induced de-novo lipogenesis in HepG2 cells. Discussion and Conclusion: All in all, these findings suggest that SHIP2 expression level is an important determinant of hepatic lipogenesis and its inhibition can potentially be a target in treatment of dyslipidemia in diabetic patients. M3 ER -