Regulation of apelin and its receptor expression in adipose tissues of obesity rats with hypertension and cultured 3T3-L1 adipocytes.
The apelin/APJ system has been implicated in obesity-related hypertension. We investigated the mechanism responsible for the pathogenesis of obesity-related hypertension with a special focus on the crosstalk between AngII/its type 1 receptor (AT1R) signaling and apelin/APJ expression. Sprague-Dawley rats fed a high-fat (obesity-related hypertension, OH) or normal-fat diet (NF) for 15 weeks were randomly assigned to one of two groups and administered vehicle or perindopril for 4 weeks. Compared to the NF rats, the OH rats showed lower levels of plasma apelin and apelin/APJ mRNAs of perirenal adipose tissues, and these changes were restored by perindopril. Administration of the AT1R antagonist olmesartan resulted in the restoration of the reduction of apelin and APJ expressions induced by AngII for 48 h in 3T3-L1 adipocytes. Among several inhibitors for extracellular signal-regulated kinases 1/2 (ERK1/2) PD98059, p38 mitogen-activated protein kinase (p38MAPK) SB203580 and phosphatidylinositol 3-kinase (PI3K) LY294002, the latter showed an additive effect on AngII-mediated inhibitory effects. In addition, the levels of p-Akt, p-ERK and p38MAPK proteins were decreased by long-term treatment with AngII (120 min), and these changes were restored by Olmesartan. Apelin/APJ appears to be impaired in obesity-related hypertension. The AngII inhibition-mediated beneficial effects are likely attributable, at least in part, to restoration of p38/ERK-dependent apelin/APJ expression in diet-induced obesity-related hypertension.
Department of Cardiology, Shanghai First People's Hospital, Shanghai Jiao Tong University, Shanghai, P.R. China.
Hongxian
H
Wu
Xian Wu
XW
Cheng
Changning
C
Hao
Zhi
Z
Zhang
Huali
H
Yao
Toyoaki
T
Murohara
Qiuyan
Q
Dai
D016475:3T3 Cells; D017667:Adipocytes / Q000378:metabolism*; D000273:Adipose Tissue / Q000378:metabolism*; D000804:Angiotensin II / Q000494:pharmacology / Q000502:physiology; D047228:Angiotensin II Type 1 Receptor Blockers / Q000494:pharmacology; D000818:Animals; D000073861:Apelin; D000075244:Apelin Receptors; D015870:Gene Expression / Q000187:drug effects / Q000235:genetics*; D005786:Gene Expression Regulation / Q000187:drug effects; D006973:Hypertension / Q000235:genetics* / Q000378:metabolism*; D007093:Imidazoles / Q000494:pharmacology; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics* / Q000378:metabolism*; D008297:Male; D051379:Mice; D019950:Mitogen-Activated Protein Kinase 1 / Q000502:physiology; D048052:Mitogen-Activated Protein Kinase 3 / Q000502:physiology; D009765:Obesity / Q000235:genetics* / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D044140:Receptor, Angiotensin, Type 1 / Q000502:physiology; D043562:Receptors, G-Protein-Coupled / Q000235:genetics* / Q000378:metabolism*; D015398:Signal Transduction / Q000235:genetics / Q000502:physiology; D013777:Tetrazoles / Q000494:pharmacology; D048051:p38 Mitogen-Activated Protein Kinases / Q000502:physiology
D047228:Angiotensin II Type 1 Receptor Blockers; D000073861:Apelin; D000075244:Apelin Receptors; C498579:Apln protein, rat; C491284:Aplnr protein, rat; D007093:Imidazoles; D036341:Intercellular Signaling Peptides and Proteins; D012333:RNA, Messenger; D044140:Receptor, Angiotensin, Type 1; D043562:Receptors, G-Protein-Coupled; D013777:Tetrazoles; D000804:Angiotensin II; C437965:olmesartan; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D048051:p38 Mitogen-Activated Protein Kinases