Volume 10, Issue 2 (Paramedical Sciences and Military Health (Autumn 2015) 2015)                   Paramedical Sciences and Military Health 2015, 10(2): 26-34 | Back to browse issues page

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Meshkani R, Gorgani-Firuzjaee S. Role of SHIP2 in Oleate Induced De-Novo Lipogenesis. Paramedical Sciences and Military Health 2015; 10 (2) :26-34
URL: http://jps.ajaums.ac.ir/article-1-54-en.html
1- Tehran University of Medical Sciences
2- AJA University of Medical sciences , gorgani59@gmail.com
Abstract:   (5407 Views)

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.

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Type of Study: Research | Subject: article abstracts
Received: 2015/11/4 | Accepted: 2015/11/26 | Published: 2015/12/21

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