Open AccessCoenzyme Q10 Improves Lipid Metabolism and Ameliorates Obesity by Regulating CaMKII-Mediated PDE4 Inhibition
Author(s) -
Zhe Xu,
Jia Huo,
Xiaoyan Ding,
Yang Mi,
Lin Li,
Jian Dai,
Kazunori Hosoe,
Hiroshi Kubo,
Masayuki Mori,
Kenichi Higuchi,
Jinko Sawashita
Publication year - 2017
Publication title -
scientific reports
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.24
H-Index - 213
ISSN - 2045-2322
DOI - 10.1038/s41598-017-08899-7
Subject(s) - coenzyme q10 , endocrinology , medicine , ampk , lipid metabolism , adipose tissue , oxidative stress , chemistry , white adipose tissue , oxidative phosphorylation , adipocyte , protein kinase a , phosphorylation , biology , biochemistry
Our recent studies revealed that supplementation with the reduced form of coenzyme Q10 (CoQ 10 H 2 ) inhibits oxidative stress and slows the process of aging in senescence-accelerated mice. CoQ 10 H 2 inhibits adipocyte differentiation and regulates lipid metabolism. In the present study, we show that dietary supplementation with CoQ 10 H 2 significantly reduced white adipose tissue content and improved the function of brown adipose tissue by regulating expression of lipid metabolism-related factors in KKAy mice, a model of obesity and type 2 diabetes. In the liver, CoQ 10 H 2 reduced cytoplasmic Ca 2+ levels and consequently inhibited the phosphorylation of CaMKII. CoQ 10 H 2 also regulated the activity of the transcription factor C-FOS and inhibited gene expression of PDE4, a cAMP-degrading enzyme, via the CaMKII-MEK1/2-ERK1/2 signaling pathway, thereby increasing intracellular cAMP. This increased cAMP activated AMPK, enhanced oxidative decomposition of lipids, and inhibited de novo synthesis of fatty acids, inhibiting the development and progression of obesity and type 2 diabetes. These results suggest that CoQ 10 H 2 supplementation may be useful as a treatment for metabolic disorders associated with obesity.