miR-27b overexpression improves mitochondrial function in a Sirt1-dependent manner
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ORIGINAL PAPER
miR-27b overexpression improves mitochondrial function in a Sirt1-dependent manner Xihong Zhou & Shengnan Zuo & Wu Xin
Received: 15 July 2015 / Accepted: 29 September 2015 # University of Navarra 2015
Abstract Resveratrol improves mitochondrial function, and recent evidences demonstrate that miRNAs play important roles in certain effects of resveratrol. In the current study, we found that a microRNA, miR-27b, was significantly induced in a dose-dependent way in skeletal muscle and C2C12 myoblast treated with resveratrol. Our results showed that overexpression of miR-27b could mimic the effects of resveratrol on improving mitochondrial function and glucose uptake in skeletal muscle cells. Subsequently, we found that FOXO1 was a potential target of miR-27b, and the effects of resveratrol on mitochondrial function were significantly affected after inhibition of miR-27b. Moreover, the effects of miR-27b on mitochondrial function were lost after inhibition of Sirt1, although miR-27b and
Xihong Zhou and Shengnan Zuo contributed equally to this work. X. Zhou (*) : W. Xin Institute of Subtropical Agriculture, Research Center for Healthy Breeding Livestock & Poultry, Hunan Engineering & Research Center for Animal & Poultry Science, Key Laboratory of Agroecology in Subtropical Region, Scientific Observing and Experimetal Station of Animal Nutrition and Feed Science in South-Central China, Ministry of Agriculture, the Chinese Academy of Sciences, 644 Yuanda Second Road, Changsha 410125 Hunan Province, People’s Republic of China e-mail: [email protected] W. Xin e-mail: [email protected] S. Zuo Clinical Laboratory Department, Hunan Guangxiu Hospital, Changsha 410000 Hunan, China
FOXO1 expression were not influenced. Taken together, these data suggested that overexpression of miR-27b could benefit mitochondrial function, while the effects of overexpressed miR-27b were Sirt1-dependent. Keywords Resveratrol . mir-27b . Sirt1 . Mitochondrial function . Glucose uptake
Introduction Resveratrol, as a natural polyphenolic compound extracted from grapes, has been proven to possess many beneficial effects, including extending lifespan [8], alleviating oxidative stress and inflammation [18], and improving glucose tolerance and insulin sensitivity [2, 11]. Among these, increasing mitochondrial biogenesis has been declared as one of the strongest and most reproducible effects of resveratrol. Sirt1, a member of the Sirtuin family, is the main target of resveratrol [8]. Resveratrol could significantly increase Sirt1 activity and then regulate peroxisome proliferator-activated receptor coactivator 1α (PGC1α) function through deacetylation [11]. Moreover, resveratrol has been established to exert its beneficial effects on mitochondrial function in a Sirt1-dependent way regardless of the dosage [16]. However, other researchers found that AMP-activated protein kinasedeficient mice are resistant to the metabolic effects of resveratrol, and they declared that resveratrol may activate Sirt1 indirectly [21]. Therefore, the specific
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