The involvement of mitochondrial dynamics in development of muscle insulin resistance

Identification: Tsai, Yau-Sheng


Description

The involvement of mitochondrial dynamics in development of muscle insulin resistance
 
Huei-Fen Jheng1, Pei-Jane Tsai2, and Yau-Sheng Tsai1
1Institute of Clinical Medicine, and 2Department of Medical Laboratory Science and Biotechnology, National Cheng Kung University, Tainan, Taiwan
 
Considering the importance of mitochondrial dynamics in mitochondrial and cellular functions, we would like to test whether obesity and excess energy intake shift the balance of mitochondrial dynamics, contributing to mitochondrial dysfunction and metabolic deterioration in skeletal muscle. First, we revealed that excess palmitate induced mitochondrial fragmentation and increased mitochondria-associated Drp1 and Fis1 in differentiated C2C12 muscle cells. This fragmentation was associated with increased oxidative stress, mitochondrial depolarization, loss of ATP production, and reduced insulin-stimulated glucose uptake. Pharmacological inhibition of Drp1 attenuated palmitate-induced mitochondrial fragmentation, oxidative stress, and insulin resistance in C2C12 cells. Furthermore, we found smaller and shorter mitochondria and increased mitochondrial fission machinery in the skeletal muscle of both genetic and diet-induced obese mice. Inhibition of mitochondrial fission improved muscle insulin signaling and systemic insulin sensitivity of obese mice. Our findings indicated that aberrant mitochondrial fission is causally associated with mitochondrial dysfunction and insulin resistance in skeletal muscle. Thus, disruption of mitochondrial dynamics may underlie the pathogenesis of muscle insulin resistance in obesity and type 2 diabetes.
 
This work is supported by grants from MOST and NHRI.

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