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.

MATERIAL/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: Mei Guo, Fu Chen, Tanfa Lin, Yanqiang Peng, Weiping Li, Xuxin Zhu, Ling Lin, Yongsong Chen
• Journal: Medical science monitor : international medical journal of experimental and clinical research (Med Sci Monit) Vol. 20 Pg. 1345-52 (Aug 01 2014) ISSN: 1643-3750 [Electronic] United States
• PMID: 25080850 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Adipokines
• Apelin
• Apln protein, mouse
• Aqp7 protein, mouse
• Aquaporins
• Azo Compounds
• Intercellular Signaling Peptides and Proteins
• Palmitates
• Phosphoinositide-3 Kinase Inhibitors
• oil red O

Topics

• 3T3-L1 Cells
• Adipocytes (drug effects, metabolism)
• Adipokines
• Analysis of Variance
• Animals
• Apelin
• Aquaporins (metabolism)
• Azo Compounds
• Gene Expression Regulation (drug effects)
• Intercellular Signaling Peptides and Proteins (metabolism, pharmacology)
• Lipid Metabolism (drug effects)
• Mice
• Palmitates
• Phosphatidylinositol 3-Kinases (metabolism)
• Phosphoinositide-3 Kinase Inhibitors
• Reverse Transcriptase Polymerase Chain Reaction