Apelin-13 Decreases Lipid Storage in Hypertrophic Adipocytes In Vitro Through the Upregulation of AQP7 Expression by the PI3K Signaling Pathway
Mei Guo, Fu Chen, Tanfa Lin, Yanqiang Peng, Weiping Li, Xuxin Zhu, Ling Lin, Yongsong Chen
Department of Endocrinology, First Affiliated Hospital, Shantou University Medical College, Shantou, China (mainland)
Med Sci Monit 2014; 20:1345-1352
Adipocyte-secreted apelin contributes to decreased adiposity and to improved insulin resistance, but the mechanisms remain unknown. The present study aimed to assess if apelin-13 is an upstream signal regulation factor of aquaporin 7 (AQP7), a water-glycerol transporter present in the plasma membrane of adipocytes that plays a key role in the regulation of lipid accumulation.
Material and Methods: 3T3-L1 pre-adipocytes were induced to fully differentiated adipocytes; hypertrophic adipocytes were then induced using palmitate. The effects of apelin-13 on AQP7 expression in hypertrophic adipocytes were investigated before and after treatment with LY249002, a PI3K inhibitor. Accumulation of cytoplasmic triglycerides (TG) in hypertrophic adipocytes was also determined.
Results: We found that 0.1 mM of palmitate induced a model of hypertrophic adipocytes with a lower AQP7 expression (0.26±0.07 vs. 0.46±0.04, P<0.05). Apelin-13 100 nM or 1000 nM upregulated AQP7 mRNA expression (100 nM: 0.54±0.06 and 1000 nM: 0.58±0.09 vs. control: 0.33±0.04, both P<0.05), and decreased accumulation of cytoplasmic triglycerides in hypertrophic adipocytes. Pretreatment using 10 µM LY294002 prevented the increase in AQP7 expression observed when using apelin-13 alone (apelin-13 + LY49002: 0.38±0.03 vs. apelin-13: 0.54±0.06, P<0.05), as well as the decreased cytoplasmic TG accumulation (apelin-13 + LY294002: 3.79±0.04 µM per µg/ml vs. apelin-13: 3.32±0.08 µM per µg/ml, P<0.05).
Conclusions: Apelin-13 decreases lipid storage in hypertrophic adipocytes in vitro, possibly through the upregulation of AQP7 expression by the PI3K signaling pathway. Treatment using apelin-13 and AQP modulators might represent novel treatment strategies against obesity and its related complications.
Keywords: Adipocytes - metabolism, 3T3-L1 Cells, Analysis of Variance, Animals, Aquaporins - metabolism, Azo Compounds, Gene Expression Regulation - drug effects, Intercellular Signaling Peptides and Proteins - pharmacology, Lipid Metabolism - drug effects, Mice, Palmitates, Phosphatidylinositol 3-Kinases - metabolism, Reverse Transcriptase Polymerase Chain Reaction