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

Abstract

Our recent studies revealed that supplementation with the reduced form of coenzyme Q10 (CoQ10H2) inhibits oxidative stress and slows the process of aging in senescence-accelerated mice. CoQ10H2 inhibits adipocyte differentiation and regulates lipid metabolism. In the present study, we show that dietary supplementation with CoQ10H2 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, CoQ10H2 reduced cytoplasmic Ca2+ levels and consequently inhibited the phosphorylation of CaMKII. CoQ10H2 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 CoQ10H2 supplementation may be useful as a treatment for metabolic disorders associated with obesity.

• Authors: Zhe Xu, Jia Huo, Xin Ding, Mu Yang, Lin Li, Jian Dai, Kazunori Hosoe, Hiroshi Kubo, Masayuki Mori, Keiichi Higuchi, Jinko Sawashita
• Journal: Scientific reports (Sci Rep) Vol. 7 Issue 1 Pg. 8253 (08 15 2017) ISSN: 2045-2322 [Electronic] England
• PMID: 28811612 (Publication Type: Journal Article)

Chemical References

• Phosphodiesterase 4 Inhibitors
• Ubiquinone
• Calcium-Calmodulin-Dependent Protein Kinase Type 2
• Cyclic Nucleotide Phosphodiesterases, Type 4
• Sarcoplasmic Reticulum Calcium-Transporting ATPases
• coenzyme Q10

Topics

• Adipocytes (drug effects, metabolism)
• Adipose Tissue, Brown (drug effects, metabolism)
• Animals
• Body Weight (drug effects)
• Calcium Signaling (drug effects)
• Calcium-Calmodulin-Dependent Protein Kinase Type 2 (metabolism)
• Cyclic Nucleotide Phosphodiesterases, Type 4 (metabolism)
• Disease Models, Animal
• Gene Expression Regulation (drug effects)
• Insulin Resistance
• Lipid Metabolism (drug effects)
• Liver (drug effects, metabolism)
• Metabolic Syndrome (drug therapy, metabolism)
• Mice
• Obesity (drug therapy, genetics, metabolism)
• Phosphodiesterase 4 Inhibitors (pharmacology)
• Sarcoplasmic Reticulum Calcium-Transporting ATPases (genetics, metabolism)
• Ubiquinone (analogs & derivatives, metabolism, pharmacology)