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Adiponectin Deficiency Accentuates High Fat Diet‐Induced Cardiac Hypertrophy and Contractile Dysfunction through Regulation of Autophagy
Author(s) -
Guo Rui,
Ren Jun
Publication year - 2012
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.26.1_supplement.137.10
Subject(s) - medicine , endocrinology , adiponectin , autophagy , cardiac function curve , adipokine , obesity , heart failure , chemistry , insulin resistance , biochemistry , apoptosis
Objectives Adiponectin (APN), an adipose‐derived adipokine, offers cardioprotective effects although the precise mechanism behind APN‐exerted beneficial action is unclear. The aim of this study was to examine if autophagy plays a role in APN‐exerted cardiac effects in high fat diet‐induced obesity. Methods Adult C57BL/6 wild‐type and APN deficient mice were fed a low (10% calorie from fat) or high fat (45% calorie from fat) diet for 22 weeks. Cardiomyocyte contractile and Ca 2+ transient properties were evaluated, including peak shortening (PS), duration and maximal velocity of shortening/relengthening (TPS/TR90, ± dL/dt), electrically stimulated change in fura‐fluorescence intensity (ΔFFI), and intracellular Ca 2+ decay rate. Myocardial function was evaluated using echocardiography. DEXA was used to evaluate adiposity. Lipid deposition was examined using myocardial histology. Energy expenditure, oxygen consumption and physical activity were monitored by metabolic cages system. Glucose tolerance test and protein markers of autophagy pathway including LC3, p62 and Beclin‐1 were also performed. Results High fat diet induced obesity, glucose intolerance, cardiac hypertrophy, dampened metabolic ability, and cardiac dysfunction, the effects of which were accentuated by APN deficiency. Furthermore, ANP deficiency augmented fat diet‐induced increased in LC3II, ratio of LC3II to LC3I and the autophagy adaptor p62, as well as decrease in Beclin‐1. Conclusions Our results revealed that APN deficiency aggravates high fat diet‐induced obesity, glucose intolerance, metabolic ability and cardiac dysfunction through decreased autophagosome formation and fusion. The research is supported by Wyoming INBRE (P20RR016474)