Coenzyme Q10 Improves Lipid Metabolism and Ameliorates Obesity by Regulating CaMKII-Mediated PDE4 Inhibition.
Coenzyme Q10 Improves Lipid Metabolism and Ameliorates Obesity by Regulating CaMKII-Mediated PDE4 Inhibition.
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DOI：
10.1038/s41598-017-08899-7
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发表时间：
2017-08-15
影响因子：
4.6
通讯作者：
Sawashita J
中科院分区：
文献类型：
--
作者：
Xu Z;Huo J;Ding X;Yang M;Li L;Dai J;Hosoe K;Kubo H;Mori M;Higuchi K;Sawashita J
我们最近的研究表明，补充还原型辅酶Q10（CoQ 10 H2）可以抑制氧化应激，减缓衰老加速小鼠的衰老过程。辅酶Q10 H2抑制脂肪细胞分化并调节脂质代谢。在本研究中，我们表明，饮食中补充辅酶Q10 H2显着降低白色脂肪组织的含量，并通过调节脂质代谢相关因子的表达，改善棕色脂肪组织的功能在KKAy小鼠，肥胖和2型糖尿病模型。在肝脏中，辅酶Q10 H2降低细胞质Ca 2+水平，从而抑制CaMKII的磷酸化。辅酶Q10 H2还通过CaMKII-MEK 1/2-ERK 1/2信号通路调节转录因子C-FOS的活性，并抑制cAMP降解酶PDE 4的基因表达，从而增加细胞内cAMP。这种增加的cAMP激活AMPK，增强脂质的氧化分解，并抑制脂肪酸的从头合成，抑制肥胖和2型糖尿病的发展和进展。这些结果表明，辅酶Q10 H2补充剂可能是有用的，作为与肥胖相关的代谢紊乱的治疗。
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.
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影响因子：
29
作者：
Chalkiadaki A;Guarente L
通讯作者：
Guarente L
影响因子：
3.5
作者：
CARLING, D;ZAMMIT, VA;HARDIE, DG
通讯作者：
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影响因子：
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作者：
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通讯作者：
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影响因子：
64.8
作者：
Kahn, Steven E.;Hull, Rebecca L.;Utzschneider, Kristina M.
通讯作者：
Utzschneider, Kristina M.
影响因子：
4
作者：
Berridge, MJ
通讯作者：
Berridge, MJ