The effects of stearidonic acid on 3T3-L1 adipocytes
Type of Degreedissertation
Nutrition and Food Science
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The n-3 polyunsaturated fatty acids (PUFAs), eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), in fish oil have been reported to have anti-obesity, anti-inflammation, and insulin-sensitizing effects. The botanical fatty acid, stearidonic acid (SDA), has been targeted as a potential biologically active surrogate for EPA. The aim of this study was to investigate whether SDA has potential anti-obesity, anti-inflammatory and insulin-sensitizing properties using the 3T3-L1 adipocyte cell culture model. In comparison to an ethanol control, SDA inhibited 3T3-L1 adipocyte differentiation by significantly decreasing (49%; P < 0.05) triglyceride accumulation, significantly decreasing (45-73%; P < 0.05) adipogenic transcription factor gene expression (C/EBPα, C/EBPβ and PPARγ), and significantly decreasing (59-96%; P < 0.05) expression of genes involved in lipid accumulation (aP2, FAS, GLUT4, LPL and SCD-1). Furthermore, SDA significantly decreased (87%; P < 0.05) 3H-thymidine incorporation during the second cycle of 3T3-L1 cell division via cell proliferation assay. To evaluate the effect of SDA on inflammation, gene expression of the inflammatory cytokine IL-6 was measured in 3T3-L1 adipocytes exposed to macrophage-derived conditioned medium pretreated with or without SDA for 24 h. Compared to BSA control, SDA significantly decreased IL-6 expression by 63% (P < 0.05). EPA and ALA decreased IL-6 expression by 41% and 39%, respectively (P < 0.05). To determine the effects of SDA on insulin sensitivity, insulin-stimulated glucose uptake assays were performed on 3T3-L1 adipocytes incubated in the absence or presence of SDA (24 h). SDA significantly increased insulin-stimulated glucose uptake by approximately 40% (P < 0.05). In addition, Western Blot analysis revealed that SDA treatment had no significant effects on insulin signaling through phosphorylation of Akt. The effect of SDA on PPARγ activity in mature adipocytes was measured by luciferase assay in HEK293 cells. SDA significantly increased transcription activity 1.8 fold (P < 0.05). EPA and DHA significantly activated the transcriptional reporter 2.6 and 2.7 fold, respectively (P < 0.05). We conclude that SDA exhibited effects on inhibiting adipocyte differentiation, attenuating inflammation, and improving insulin sensitivity in 3T3-L1 adipocytes. Thus, SDA could be a botanical source of n-3 PUFA in the treatment of obesity and type 2 diabetes.