4.7 Article

DHA-Provoked Reduction in Adipogenesis and Glucose Uptake Could Be Mediated by Gps2 Upregulation in Immature 3T3-L1 Cells

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MDPI
DOI: 10.3390/ijms241713325

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docosahexaenoic acid (DHA); cell viability; adipogenesis; lipolysis rate; glucose uptake; Pparg; Gpr120; Gps2; Cpt1

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This study examines the effect of docosahexaenoic acid (DHA) on adipogenesis in 3T3-L1 cells. The results show that DHA inhibits adipogenesis, lipolysis, and glucose uptake by suppressing Pparg and Gpr120 gene expression. This challenges the conventional belief that omega-3 fatty acids promote adipogenesis and enhance insulin-dependent glucose cell flux.
The signaling pathway of fatty acids in the context of obesity is an extensively explored topic, yet their primary mechanism of action remains incompletely understood. This study aims to examine the effect of docosahexaenoic acid (DHA) on some crucial aspects of adipogenesis in differentiating 3T3-L1 cells, using palmitic acid-treated (PA), standard differentiated, and undifferentiated adipocytes as controls. Employing 60 & mu;M DHA or PA, 3T3-L1 preadipocytes were treated from the onset of adipogenesis, with negative and positive controls included. After eight days, we performed microscopic observations, cell viability assays, the determination of adiponectin concentration, intracellular lipid accumulation, and gene expression analysis. Our findings demonstrated that DHA inhibits adipogenesis, lipolysis, and glucose uptake by suppressing peroxisome proliferator-activated receptor gamma (Pparg) and G-protein coupled receptor 120 (Gpr120) gene expression. Cell cytotoxicity was ruled out as a causative factor, and & beta;-oxidation involvement was suspected. These results challenge the conventional belief that omega-3 fatty acids, acting as Pparg and Gpr120 agonists, promote adipogenesis and enhance insulin-dependent glucose cell flux. Moreover, we propose a novel hypothesis suggesting the key role of the co-repressor G protein pathway suppressor 2 in mediating this process. Additional investigations are required to elucidate the molecular mechanisms driving DHA's anti-adipogenic effect and its broader health implications.

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