Cardiac hypertrophy-related pathways in obesity.
Obesity is often associated with the development of cardiac hypertrophy but the hypertrophy-related pathways in obesity remain unknown. The purpose of this study was to evaluate cardiac hypertrophy-related markers, atrial natriuretic peptide (ANP), B-type natriuretic peptide (BNP), tumor necrosis factor-alpha (TNFα) and hypertrophy-related pathways, interleukin (IL)-6-STAT3, IL-6-MEK5-ERK5 and calcineurin-nuclear factor of activated T-cells (NFAT)3 in the excised hearts from obese rats. Twelve obese Zucker rats were studied at 5-6 months of age and twelve age-matched lean Zucker rats served as the control group. The cardiac characteristics, myocardial architecture, ANP, BNP, TNFα levels, IL-6, STAT3, p-STAT3, MEK5, ERK-5, p-ERK-5, calcineurin and NFAT3 in the left ventricle from the rats were measured by heart weight index, echocardiography, vertical cross section, histological analysis, reverse transcription polymerase chain reaction and western blotting. Compared with the lean control, the whole heart weight, the left ventricule weight, the ratio of the whole heart weight to tibia length, echocardiographic interventricular septum, left ventricular posterior wall thickness, myocardial morphological changes and systolic blood pressure were found to increase in the obese rats. The protein levels of ANP, BNP, TNFα, IL-6, STAT3, p-STAT3, MEK-5, ERK-5, p-ERK 5, calcineurin and NFAT3 were also significantly increased in the hearts of the obese rats. The results showed that the hypertrophy-related markers, ANP, BNP and TNFα, the hypertrophy-related pathways IL-6-STAT3 and IL-6-MEK5-ERK5, and the calcineurin-NFAT3 hypertrophy-related pathways were more active in obese Zucker rats, which may provide possible hypertrophic mechanisms for developing cardiac hypertrophy and pathological changes in obesity.
Graduate Institute of Clinical Medical Science, China Medical University, Taichung 40440, Taiwan, Republic of China.
Wei-Kung
WK
Chen
Yu-Lan
YL
Yeh
Yueh-Min
YM
Lin
Jing-Ying
JY
Lin
Bor-Show
BS
Tzang
James A
JA
Lin
Ai-Lun
AL
Yang
Fong-Li
FL
Wu
Fuu-Jen
FJ
Tsai
Shiu-Min
SM
Cheng
Chih-Yang
CY
Huang
Shin-Da
SD
Lee
D000818:Animals; D009320:Atrial Natriuretic Factor / Q000378:metabolism; D006332:Cardiomegaly / Q000150:complications* / Q000235:genetics / Q000378:metabolism*; D004195:Disease Models, Animal; D015850:Interleukin-6 / Q000378:metabolism; D048671:MAP Kinase Kinase 5 / Q000378:metabolism; D020935:MAP Kinase Signaling System / Q000502:physiology*; D008297:Male; D048054:Mitogen-Activated Protein Kinase 7 / Q000378:metabolism; D020097:Natriuretic Peptide, Brain / Q000378:metabolism; D009767:Obesity, Morbid / Q000150:complications* / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D011924:Rats, Zucker; D020133:Reverse Transcriptase Polymerase Chain Reaction; D050796:STAT3 Transcription Factor / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D015850:Interleukin-6; D012333:RNA, Messenger; D050796:STAT3 Transcription Factor; C494088:Stat3 protein, rat; D014409:Tumor Necrosis Factor-alpha; D020097:Natriuretic Peptide, Brain; D009320:Atrial Natriuretic Factor; D048054:Mitogen-Activated Protein Kinase 7; D048671:MAP Kinase Kinase 5; C482565:Map2k5 protein, rat