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

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.