Leucine regulates slow‐twitch muscle fibers expression and mitochondrial function by Sirt1/AMPK signaling in porcine skeletal muscle satellite cells

Abstract

A previous study demonstrated that leucine upregulates the slow myosin heavy chain mRNA expression in C2C12 cells. However, the role of leucine in slow-twitch muscle fibers expression and mitochondrial function of porcine skeletal muscle satellite cells as well as its mechanism remain unclear. In this study, porcine skeletal muscle satellite cells cultured in differentiation medium were treated with 2 mM leucine for 3 days. Sirt1 inhibitor EX527, AMPK inhibitor compound C, and AMPKα1 siRNA were used to examine its underlying mechanism. Here we showed that leucine increased slow-twitch muscle fibers and mitochondrial function-related gene expression, as well as increased succinic dehydrogenase (SDH) and malate dehydrogenase (MDH) activities. Moreover, leucine increased the protein levels of Sirt1 and phospho-AMPK. We also found that AMPKα1 siRNA, AMPK inhibitor compound C, or Sirt1 inhibitor EX527 attenuated the positive effect of leucine on slow-twitch muscle fibers and mitochondrial function-related gene expression. Finally, we showed that Sirt1 was required for leucine-induced AMPK activation. Our results provide, for the first time, evidence that leucine induces slow-twitch muscle fibers expression and improves mitochondrial function through Sirt1/AMPK signaling pathway in porcine skeletal muscle satellite cells. K E Y W O R D Sleucine, mitochondrial function, porcine skeletal muscle satellite cells, Sirt1/AMPK, slowtwitch muscle fibers expression

Arginine promotes porcine type I muscle fibres formation through improvement of mitochondrial biogenesis

“…PGC-1α, a major regulator of mitochondrial biogenesis, is expressed in skeletal muscle (27) . Sirt1 modulates PGC-1α expression and activity (28) and plays an important role in regulating mitochondrial function (29,30) . PGC-1α and Sirt1 control mitochondrial biogenesis and function via the induction and activation of several downstream nuclear transcription factors, such as NRF1, mitochondria transcription factor B1 (TFB1M), ATP5G and cytochrome c (Cytc) (6,29,31) .…”

“…Type I (slow-twitch) muscle fibres are rich in the mitochondria (3,32) . It has been reported that some nutrients (such as leucine and resveratrol) can regulate type I (slowtwitch) muscle fibres expression by improving the mitochondrial biogenesis and function (29,30,33) . In the present study, our data found that dietary supplementation of 1•0 % Arg significantly increased the PGC-1α, Sirt1 and Cytc protein expressions, the PGC-1α, NRF1, TFB1M, Cytc and ATP5G mRNA expressions and the mtDNA content, suggesting that Arg plays an important role in regulating mitochondrial biogenesis and function.…”

Coordinated Modulation of Energy Metabolism and Inflammation by Branched-Chain Amino Acids and Fatty Acids

“…In addition, both BCAA mixture and leucine could increase the mitochondrial content and induce the expression of TFAM and mitochondrial component genes. However, several studies have shown that valine did not affect the mitochondrial biogenesis ( 49 , 51 , 52 ).…”

PGC-1α-Targeted Therapeutic Approaches to Enhance Muscle Recovery in Aging

“…These results suggest that in skeletal muscle, leucine-induced PGC-1α expression depends on mTORC1 but a feedback loop involving mTORC1 and PGC-1α may also exist. Interestingly, piglet primary muscle cells treated with leucine for 3 days increased PGC-1α protein and mRNA (and promoted slow myosin heavy chain phenotype) yet was dependent on SIRT1 and AMPKα [ 61 ]. Similarly, C2C12 myotubes treated with leucine for 24 or 48 h also required SIRT1 and AMPKα to increase PGC-1α mRNA [ 55 ].…”