Open AccessHigh‐fat diet induces cardiac remodelling and dysfunction: assessment of the role played by SIRT 3 loss
Author(s) -
Zeng Heng,
Vaka Venkata Ramana,
He Xiaochen,
Booz George W.,
Chen JianXiong
Publication year - 2015
Publication title -
journal of cellular and molecular medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.44
H-Index - 130
eISSN - 1582-4934
pISSN - 1582-1838
DOI - 10.1111/jcmm.12556
Subject(s) - endocrinology , medicine , cardiac function curve , reactive oxygen species , knockout mouse , obesity , biology , hypoxia (environmental) , heart failure , mitochondrial ros , muscle hypertrophy , chemistry , oxidative stress , microbiology and biotechnology , oxygen , receptor , organic chemistry
Mitochondrial dysfunction plays an important role in obesity‐induced cardiac impairment. SIRT 3 is a mitochondrial protein associated with increased human life span and metabolism. This study investigated the functional role of SIRT 3 in obesity‐induced cardiac dysfunction. Wild‐type ( WT ) and SIRT 3 knockout ( KO ) mice were fed a normal diet ( ND ) or high‐fat diet ( HFD ) for 16 weeks. Body weight, fasting glucose levels, reactive oxygen species ( ROS ) levels, myocardial capillary density, cardiac function and expression of hypoxia‐inducible factor ( HIF )‐1α/‐2α were assessed. HFD resulted in a significant reduction in SIRT 3 expression in the heart. Both HFD and SIRT 3 KO mice showed increased ROS formation, impaired HIF signalling and reduced capillary density in the heart. HFD induced cardiac hypertrophy and impaired cardiac function. SIRT 3 KO mice fed HFD showed greater ROS production and a further reduction in cardiac function compared to SIRT 3 KO mice on ND . Thus, the adverse effects of HFD on cardiac function were not attributable to SIRT 3 loss alone. However, HFD did not further reduce capillary density in SIRT 3 KO hearts, implicating SIRT 3 loss in HFD ‐induced capillary rarefaction. Our study demonstrates the importance of SIRT 3 in preserving heart function and capillary density in the setting of obesity. Thus, SIRT 3 may be a potential therapeutic target for obesity‐induced heart failure.