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Int J Biol Sci 2017; 13(9):1152-1162. doi:10.7150/ijbs.20132 This issue Cite

Research Paper

Skeletal Muscle-Specific Overexpression of PGC-1α Induces Fiber-Type Conversion through Enhanced Mitochondrial Respiration and Fatty Acid Oxidation in Mice and Pigs

Lin Zhang¹, Ying Zhou¹, Wangjun Wu³, Liming Hou¹, Hongxing Chen⁴, Bo Zuo¹, Yuanzhu Xiong^1✉, Jinzeng Yang^{1, 2✉}

1. Key Laboratory of Swine Genetics and Breeding of the Ministry of Agriculture, College of Animal Sciences, Huazhong Agricultural University, Wuhan 430070, China;
2. Department of Human Nutrition, Food and Animal Sciences, University of Hawaii at Manoa, Honolulu, Hawaii 96822, USA;
3. College of Animal Science and Technology, Nanjing Agricultural University, Nanjing 210095, China;
4. Beijing Institute of Biotechnology, Beijing 100071, China.

✉ Corresponding authors: jinzengedu, xiongyzycom

Abstract

Individual skeletal muscles in the animal body are heterogeneous, as each is comprised of different fiber types. Type I muscle fibers are rich with mitochondria, and have high oxidative metabolisms while type IIB fibers have few mitochondria and high glycolytic metabolic capacity. Peroxisome proliferator-activated receptor gamma coactivator 1α (PGC-1α), a transcriptional co-activator that regulates mitochondrial biogenesis and respiratory function, is implicated in muscle fiber-type switching. Over-expression of PGC-1α in transgenic mice increased the proportion of red/oxidative type I fiber. During pig muscle growth, an increased number of type I fibers can give meat more red color. To explore the roles of PGC-1α in regulation of muscle fiber type conversion, we generated skeletal muscle-specific PGC-1α transgenic mice and pig. Ectopic over-expression of PGC-1α was detected in both fast and slow muscle fibers. The transgenic animals displayed a remarkable amount of red/oxidative muscle fibers in major skeletal muscle tissues. Skeletal muscles from transgenic mice and pigs have increased expression levels of oxidative fiber markers such as MHC1, MHC2x, myoglobin and Tnni1, and decreased expressions of glycolytic fiber genes (MHC2a, MHC2b, CASQ-1 and Tnni2). The genes responsible for the TCA cycle and oxidative phosphorylation, cytochrome coxidase 2 and 4, and citrate synthase were also increased in the transgenic mice and pigs. These results suggested that transgenic over-expressed PGC-1α significantly increased muscle mitochondrial biogenesis, resulting in qualitative changes from glycolytic to oxidative energy generation. The transgenic animals also had elevated levels of PDK4 and PPARγ proteins in muscle tissue, which can lead to increased glycogen deposition and fatty acid oxidation. Therefore, the results support a significant role of PGC-1α in conversion of fast glycolytic fibers to slow and oxidative fiber through enhanced mitochondrial respiration and fatty acid oxidation, and transgenic over-expression of PGC-1α in skeletal muscle leads to more red meat production in pigs.

Keywords: PGC-1α, mitochondria biogenesis, fiber type conversion, transgenic pig.

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