Open AccessFGF 21 deletion exacerbates diabetic cardiomyopathy by aggravating cardiac lipid accumulation
Author(s) -
Yan Xiaoqing,
Chen Jun,
Zhang Chi,
Zhou Shanshan,
Zhang Zhiguo,
Chen Jing,
Feng Wenke,
Li Xiaokun,
Tan Yi
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.12530
Subject(s) - fgf21 , diabetic cardiomyopathy , medicine , endocrinology , cd36 , oxidative stress , streptozotocin , diabetes mellitus , lipid metabolism , cardiac fibrosis , cardiomyopathy , biology , fibroblast growth factor , receptor , fibrosis , heart failure
Fibroblast growth factor 21 ( FGF 21) plays an important role in energy homoeostasis. The unaddressed question of FGF 21's effect on the development and progression of diabetic cardiomyopathy (DCM) is investigated here with FGF 21 knockout ( FGF 21 KO ) diabetic mice. Type 1 diabetes was induced in both FGF 21 KO and C57 BL /6J wild‐type ( WT ) mice via streptozotocin. At 1, 2 and 4 months after diabetes onset, the plasma FGF 21 levels were significantly decreased in WT diabetic mice compared to controls. There was no significant difference between FGF 21 KO and WT diabetic mice in blood glucose and triglyceride levels. FGF 21 KO diabetic mice showed earlier and more severe cardiac dysfunction, remodelling and oxidative stress, as well as greater increase in cardiac lipid accumulation than WT diabetic mice. Western blots showed that increased cardiac lipid accumulation was accompanied by further increases in the expression of nuclear factor (erythroid‐derived 2)‐like 2 (Nrf2) and its target protein CD 36, along with decreases in the phosphorylation of AMP ‐activated protein kinase and the expression of hexokinase II and peroxisome proliferator‐activated receptor gamma co‐activator 1α in the heart of FGF 21 KO diabetic mice compared to WT diabetic mice. Our results demonstrate that FGF 21 deletion‐aggravated cardiac lipid accumulation is likely mediated by cardiac Nrf2‐driven CD 36 up‐regulation, which may contribute to the increased cardiac oxidative stress and remodelling, and the eventual development of DCM . These findings suggest that FGF 21 may be a therapeutic target for the treatment of DCM .