title: Apelin-13 decreases lipid storage in hypertrophic adipocytes in vitro through the upregulation of AQP7 expression by the PI3K signaling pathway.
abstract: BACKGROUND
  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.
  
  
  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.
authors: Department of Endocrinology, First Affiliated Hospital, Shantou University Medical College, Shantou, China (mainland).
authors: Mei
authors: M
authors: Guo
authors: Department of Endocrinology, First Affiliated Hospital, Shantou University Medical College, Shantou, China (mainland).
authors: Fu
authors: F
authors: Chen
authors: Department of Endocrinology, First Affiliated Hospital, Shantou University Medical College, Shantou, China (mainland).
authors: Tanfa
authors: T
authors: Lin
authors: Department of Nephrology, First Affiliated Hospital, Shantou University Medical College, Shantou, China (mainland).
authors: Yanqiang
authors: Y
authors: Peng
authors: Department of Endocrinology, First Affiliated Hospital, Shantou University Medical College, Shantou, China (mainland).
authors: Weiping
authors: W
authors: Li
authors: Department of Endocrinology, First Affiliated Hospital, Shantou University Medical College, Shantou, China (mainland).
authors: Xuxin
authors: X
authors: Zhu
authors: Department of Rheumatolog, First Affiliated Hospital, Shantou University Medical College, Shantou, China (mainland).
authors: Ling
authors: L
authors: Lin
authors: Department of Endocrinology, First Affiliated Hospital, Shantou University Medical College, Shantou, China (mainland).
authors: Yongsong
authors: Y
authors: Chen
mesh_terms: D041721:3T3-L1 Cells; D017667:Adipocytes / Q000187:drug effects / Q000378:metabolism*; D054392:Adipokines; D000704:Analysis of Variance; D000818:Animals; D000073861:Apelin; D020346:Aquaporins / Q000378:metabolism*; D001391:Azo Compounds; D005786:Gene Expression Regulation / Q000187:drug effects*; D036341:Intercellular Signaling Peptides and Proteins / Q000378:metabolism* / Q000494:pharmacology; D050356:Lipid Metabolism / Q000187:drug effects*; D051379:Mice; D010168:Palmitates; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D000081082:Phosphoinositide-3 Kinase Inhibitors; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D054392:Adipokines; D000073861:Apelin; D020346:Aquaporins; D001391:Azo Compounds; D036341:Intercellular Signaling Peptides and Proteins; D010168:Palmitates; D019869:Phosphatidylinositol 3-Kinases; D000081082:Phosphoinositide-3 Kinase Inhibitors; C402826:Apln protein, mouse; C491927:Aqp7 protein, mouse; C011049:oil red O