title: Aldosterone directly affects apelin expression and secretion in adipocytes.
abstract: There is a high incidence of metabolic syndrome among patients with primary aldosteronism (PA), which has recently been associated with an unfavorable cardiometabolic profile. However, the underlying mechanisms have not been clarified in detail. Characterizing aldosterone (Ald) target genes in adipocytes will help us to elucidate the deleterious effects associated with excess Ald. Apelin, a novel adipokine, exerts beneficial effects on obesity-associated disorders and cardiovascular homeostasis. The objective of this study was to investigate the effects of high Ald levels on apelin expression and secretion and the underlying mechanisms involved in adipocytes. In vivo, a single-dose Ald injection acutely decreased apelin serum levels and adipose tissue apelin production, which demonstrates a clear inverse relationship between the levels of plasma Ald and plasma apelin. Experiments using 3T3-L1 adipocytes showed that Ald decreased apelin expression and secretion in a time- and dose-dependent manner. This effect was reversed by glucocorticoid receptor (GR) antagonists or GR (NR3C1) knockdown; furthermore, putative HREs were identified in the apelin promoter. Subsequently, we verified that both glucocorticoids and mineralocorticoids regulated apelin expression through GR activation, although no synergistic effect was observed. Additionally, detailed potential mechanisms involved a p38 MAPK signaling pathway. In conclusion, our findings strengthen the fact that there is a direct interaction between Ald and apelin in adipocytes, which has important implications for hyperaldosteronism or PA-associated cardiometabolic syndrome and hoists apelin on the list of potent therapeutic targets for PA.
authors.affiliation: State Key Laboratory of Medical Genomics, Shanghai Institute of Endocrinology and Metabolism, Molecular Medicine Center, Shanghai Jiaotong University School of Medicine, Shanghai 200025, China.
authors.forename: He
authors.initials: H
authors.lastname: Jiang
authors.forename: Xiao-Ping
authors.initials: XP
authors.lastname: Ye
authors.forename: Zhong-Yin
authors.initials: ZY
authors.lastname: Yang
authors.forename: Ming
authors.initials: M
authors.lastname: Zhan
authors.forename: Hai-Ning
authors.initials: HN
authors.lastname: Wang
authors.forename: Huang-Min
authors.initials: HM
authors.lastname: Cao
authors.forename: Hui-Jun
authors.initials: HJ
authors.lastname: Xie
authors.forename: Chun-Ming
authors.initials: CM
authors.lastname: Pan
authors.forename: Huai-Dong
authors.initials: HD
authors.lastname: Song
authors.forename: Shuang-Xia
authors.initials: SX
authors.lastname: Zhao
mesh_terms: D041721:3T3-L1 Cells; D017667:Adipocytes / Q000187:drug effects* / Q000378:metabolism*; D054392:Adipokines; D000450:Aldosterone / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D000073861:Apelin; D004305:Dose-Response Relationship, Drug; D005786:Gene Expression Regulation / Q000187:drug effects*; D005938:Glucocorticoids / Q000494:pharmacology; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics* / Q000378:metabolism*; D008297:Male; D051379:Mice; D008901:Mineralocorticoids / Q000494:pharmacology; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
chemical_list: D054392:Adipokines; D000073861:Apelin; C402826:Apln protein, mouse; D005938:Glucocorticoids; D036341:Intercellular Signaling Peptides and Proteins; D008901:Mineralocorticoids; D012333:RNA, Messenger; D000450:Aldosterone; D048051:p38 Mitogen-Activated Protein Kinases
keywords: 3T3-L1 adipocyte; aldosterone; apelin; glucocorticoid receptor; p38 MAPK