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Melanocortin 4 Receptor Activation Attenuates Mitochondrial Dysfunction in Skeletal Muscle of Diabetic Rats
Author(s) -
Zhang HaoHao,
Liu Jiao,
Qin GuiJun,
Li XiaLian,
Du PeiJie,
Hao Xiao,
Zhao Di,
Tian Tian,
Wu Jing,
Yun Meng,
Bai YanHui
Publication year - 2017
Publication title -
journal of cellular biochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.028
H-Index - 165
eISSN - 1097-4644
pISSN - 0730-2312
DOI - 10.1002/jcb.26062
Subject(s) - mitochondrial biogenesis , ampk , skeletal muscle , endocrinology , medicine , oxidative stress , amp activated protein kinase , mitochondrion , melanocortin , sirtuin 1 , chemistry , biology , microbiology and biotechnology , protein kinase a , phosphorylation , biochemistry , downregulation and upregulation , hormone , gene
A previous study has confirmed that the central melanocortin system was able to mediate skeletal muscle AMP‐activated protein kinase (AMPK) activation in mice fed a high‐fat diet, while activation of the AMPK signaling pathway significantly induced mitochondrial biogenesis. Our hypothesis was that melanocortin 4 receptor (MC4R) was involved in the development of skeletal muscle injury in diabetic rats. In this study, we treated diabetic rats intracerebroventricularly with MC4R agonist R027‐3225 or antagonist SHU9119, respectively. Then, we measured the production of reactive oxygen species (ROS), the levels of malondialdehyde (MDA) and glutathione (GSH), the mitochondrial DNA (mtDNA) content and mitochondrial biogenesis, and the protein levels of p‐AMPK, AMPK, peroxisome proliferator‐activated receptor‐gamma coactivator 1α (PGC‐1α), sirtuin 1 (SIRT1), and manganese superoxide dismutase (MnSOD) in the skeletal muscle of diabetic rats. The results showed that there was significant skeletal muscle injury in the diabetic rats along with serious oxidative stress and decreased mitochondrial biogenesis. Treatment with R027‐3225 reduced oxidative stress and induced mitochondrial biogenesis in skeletal muscle, and also activated the AMPK‐SIRT1‐PGC‐1α signaling pathway. However, diabetic rats injected with MC4R antagonist SHU9119 showed an aggravated oxidative stress and mitochondrial dysfunction in skeletal muscle. In conclusion, our results revealed that MC4R activation was able to attenuate oxidative stress and mitochondrial dysfunction in skeletal muscle induced by diabetes partially through activating the AMPK‐SIRT1‐PGC‐1α signaling pathway. J. Cell. Biochem. 118: 4072–4079, 2017. © 2017 Wiley Periodicals, Inc.