Scientists reveal a novel role of miR-182 in glucose homeostasis
Skeletal muscles are composed of different types of fibers exhibiting distinct contractile and metabolic properties. It has been widely accepted that changes in skeletal muscle fiber types and metabolic types have great impact on energy metabolism. Understanding the molecular mechanisms involved in the regulation of fiber-type specification and metabolic switch in skeletal muscle provides insights into the development of metabolic diseases.
Metabolic flexibility is the capacity for the organism to adapt fuel oxidation to fuel availability. When insulin is secreted, the major energy source for skeletal muscle is switched from fatty acids to carbohydrates. However, the metabolic flexibility is impaired significantly in skeletal muscles of type 2 diabetic patients.
Ying Hao, a principal investigator at the Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, and his group members Zhang Duo and Li Yan collaborated with Jin Zibing, a professor at Wenzhou Medical University, and indentified an important miRNA in the regulation of skeletal muscle fiber type transition and metabolic flexibility. They found that miR-182 is enriched in fast-twitch muscles and its expression level negatively correlates with blood glucose level. MiR-182 knockout mice not only display muscle loss and fast-to-slow fiber types witching, but also exhibit impaired glucose tolerance. Mechanistic studies reveal that miR-182 controls glucose homeostasis by modulating fuel selection through FoxO1/PDK4/PDHC. Interestingly, short-time HFD feeding is able to reduce miR-182 level by TNFα in muscle, which might ultimately contribute to the upregulation of FoxO1/PDK4, metabolic inflexibility, and abnormal glucose homeostasis. Importantly, restoration of miR-182 expression in HFD-fed mice is capable of promoting a switch from slow to fast muscle phenotype and improving the glucose metabolism. Taken together, this work establishes miR-182 as a critical regulator which confers the robust and precise controls on fuel usage and glucose homeostasis and also demonstrates that a metabolic shift toward a faster and more glycolytic phenotype is beneficial for glucose control in diabetic state.
This work was published online in Cell Reports on July 7, 2016, as a research article entitled “miR-182 regulates metabolic homeostasis through modulating glucose utilization in muscles”.
MiR-182 is highly expressed in fast-twitch muscle. It modulates glucose utilization in muscle by targeting FoxO1 and PDK4, which control fuel selection via PDHC.
Image by Dr. Ying’s lab
Ying Hao, Ph.D.
Professor and Principle Investigator
Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, CAS, 320 Yueyang Road, Shanghai, China 200031