Adiponectin knockout accentuates high fat diet-induced obesity and cardiac dysfunction: Role of autophagy

BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE

卷:1832

Article

Guo, Rui¹  Zhang, Yingmei^1,2  Turdi, Subat¹  Ren, Jun^1,2 

[1] Univ Wyoming, Coll Hlth Sci, Ctr Cardiovasc Res & Alternat Med, Laramie, WY 82071 USA

[2] Fourth Mil Med Univ, Dept Cardiol, Xijing Hosp, Xian 710032, Peoples R China

关键词: Adiponectin;    Autophagy;    Cardiac function;    Hypertrophy;    Metabolism;    Obesity;   

DOI  :  10.1016/j.bbadis.2013.03.013

来源: Elsevier

【 摘 要 】

Adiponectin (APN), an adipose-derived adipokine, offers cardioprotective effects although the precise mechanism of action remains unclear. This study was designed to examine the role of APN in high fat diet-induced obesity and cardiac pathology. Adult C57BL/6 wild-type and APN knockout mice were fed a low or high fat diet for 22 weeks. After 40 day feeding, mice were treated with 2 mg/kg rapamycin or vehicle every other day for 42 days on respective fat diet. Cardiomyocyte contractile and Ca2+ transient properties were evaluated. Myocardial function was evaluated using echocardiography. Dual energy X-ray absorptiometry was used to evaluate adiposity. Energy expenditure, metabolic rate and physical activity were monitored using a metabolic cage. Lipid deposition, serum triglyceride, glucose tolerance, markers of autophagy and fatty acid metabolism including LC3, p62, Beclin-1, AMPK, mTOR, fatty acid synthase (FAS) were evaluated. High fat diet intake induced obesity, systemic glucose intolerance, cardiac hypertrophy, dampened metabolic ability, cardiac and intracellular Ca2+ derangements, the effects of which were accentuated by APN knockout Furthermore, APN deficiency augmented high fat diet-induced upregulation in the autophay adaptor p62 and the decline in AMPK without affecting high fat diet-induced decrease in LC3II and LC3II-to-LC3I ratio. Neither high fat diet nor APN deficiency altered Beclin-1. Interestingly, rapamycin negated high fat diet-induced/APN-deficiency-accentuated obesity, cardiac hypertrophy and contractile dysfunction as well as AMPK dephosphorylation, mTOR phosphorylation and p62 buildup. Our results collectively revealed that APN deficiency may aggravate high fat diet-induced obesity, metabolic derangement, cardiac hypertrophy and contractile dysfunction possibly through decreased myocardial autophagy. (C) 2013 Elsevier B.V. All rights reserved.

【 授权许可】

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