MicroRNA-27b Overexpression Improves Mitochondrial Function and Insulin Resistance
Mitochondria are the principal energy sources of the cell that convert nutrients into energy through cellular respiration. Mitochondrial dysfunction has been linked to numerous diseases, especially obesity, type 2 diabetes and insulin resistance, which are pandemic in developed and developing nations and are of great public health concern.
Resveratrol, as a natural polyphenolic compound extracted from grapes, has been proved to possess many beneficial effects, including alleviating oxidative stress and inflammation, improving glucose tolerance and insulin sensitivity. Among these, increasing mitochondrial biogenesis has been declared as one of the strongest and most reproducible effects. However, the specific molecular mechanism that resveratrol modulates mitochondrial function remains to be a little controversial. Some reports that resveratrol exerted its beneficial effects on mitochondrial function in a Sirt1-dependent way. However, others demonstrated that AMP-activated protein kinase, adenosine monophosphate activated protein kinase(AMP-activated) protein kinase-deficient mice are resistant to the metabolic effects of resveratrol, and they declared that resveratrol may activate silent information regulator factor 1(Sirt1) indirectly.
Recently, researchers in the Institute of Subtropical Agriculture, Chinese Academy of Sciences (ISA) and Clinical Laboratory Department, Hunan Guangxiu Hospital studied the effects of MicroRNA-27b (MiR-27b)-a target of resveratrol, on mitochondrial function in skeletal muscle and C2C12 cell myoblast.
The study was carried out in fifty male C57BL/6J mice at the age of 10 weeks, researchers found that MiR-27b expression was significantly higher in high-fat fed mice supplemented with resveratrol and overexpression of miR-27b could mimic the effects of resveratrol on improving mitochondrial function and glucose uptake in skeletal muscle cells. Subsequently, the researchers also found a potential target of miR-27b, foxo1, 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 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. These results shed a new light for resveratrol treatment, especially on insulin resistance and type 2 diabetes, by manipulating certain miRNAs in parallel with related regulatory factors.
The research was financially supported by the National Science and Technology Support Program Funding (2012BAD39B03).The study entitled MiR-27b overexpression improves mitochondrial function in a Sirt1-dependent manner?has been published in Volume 71, Issue 4, December 2015 of Journal of Physiology and Biochemistry, details could be found at http://link.springer.com/article/10.1007%2Fs13105-015-0439-3
Contact: ZHOU Xihong
E-mail: xhzhou@isa.ac.cn
Institute of Subtropical Agriculture, Chinese Academy of Sciences
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