Blockade of the Renin-Angiotensin System Ameliorates Apelin Production in 3T3-L1 Adipocytes
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Angiotensin II (Ang II), the physiologically-active product of the renin-angiotensin system (RAS), has recently been found to be an adipokine secreted by adipocytes. Although Ang II is known to exert its effects via angiotensin II receptor type 1 (AT1R) or type 2 (AT2R), the roles of the two receptors in the adipose tissue are unclear. Apelin, another adipokine, has been found able to restore glucose tolerance in obese and insulin-resistant mice. Because they are both involved in metabolic disorders, there may be an interaction between the two adipokines.
To observe the expression of RAS and apelin, 3T3-L1 adipocytes were harvested after 1, 2, 4, and 6 days of differentiation. The RAS blockers captopril (10−4 M), perindopril (10−3 M), losartan (10−4 M), or PD123319 (10−4 M) were added at day 2 of differentiation and harvested at day 4 and 6, when apelin expression was measured. Expressions of mRNAs were detected by real-time PCR. Production of Ang II and apelin was measured from culture media by ELISA. Cellular lipid droplets were detected by oil-red staining.
Our study showed that the mRNA expressions of AGT, renin, ACE1, and AT2R were up-regulated while AT1R mRNA was down-regulated during adipogenesis. Apelin expression increased during adipogenesis, and this increase was further augmented by blocking RAS. RAS blockers also prevented excessive lipid accumulation and the generation of ROS (reactive oxygen species) in differentiating adipocytes.
Our study suggests that RAS blockers achieve their beneficial effects by their enhancement of adipocyte secretion of apelin.
Key wordsAdipocyte Adipokine Angiotensinogen Angiotensin-converting enzyme inhibitor Angiotensin receptor blocker
This work was supported by grants from the Kaohsiung Municipal Hsiao-Kang Hospital (KMHK-95-040; KMHK-97-016) and the Medical Research Fund of Kaohsiung Medical University (QM094009), Taiwan. We also thank SERVIER and MERCK for providing the perindopril and losartan used in this study.
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