Coenzyme Q10 Improves Lipid Metabolism and Ameliorates Obesity by Regulating CaMKII-Mediated PDE4 Inhibition

• Published in: Scientific reports Vol. 7; no. 1; pp. 8253 - 12
• Main Authors: Xu, Zhe, Huo, Jia, Ding, Xin, Yang, Mu, Li, Lin, Dai, Jian, Hosoe, Kazunori, Kubo, Hiroshi, Mori, Masayuki, Higuchi, Keiichi, Sawashita, Jinko
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 15.08.2017; Nature Publishing Group; Nature Portfolio
• Subjects: 14/19; 45/15; 45/77; 631/80/86; 692/699/317; 82/1; 82/29; Adipose tissue; Adipose tissue (brown); c-Fos protein; Ca2+/calmodulin-dependent protein kinase II; Calcium; Coenzyme Q10; Cyclic AMP; Diabetes; Diabetes mellitus; Dietary supplements; Fatty acids; Gene expression; Humanities and Social Sciences; Intracellular signalling; Lipid metabolism; Lipids; Liver; Metabolic disorders; Metabolism; multidisciplinary; Obesity; Oxidative stress; Phosphodiesterase; Phosphorylation; Science; Science (multidisciplinary); Senescence; Signal transduction
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-017-08899-7

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.