The role of sirtuins in the regulation of metabolic homeostasis in skeletal muscle

Purpose of review To discuss recent findings regarding the role of the histone deacetylase sirtuin SirT1 in anabolic and catabolic signaling pathways in skeletal muscle. Recent findings Since its discovery as a regulator of peroxisome proliferator-activated receptor g-coactivator 1 alpha transcriptional activity, SirT1 has received much attention for its role in the regulation of tissue-specific and whole body regulation of metabolic processes. Although these early seminal discoveries identified SirT1 as a central player in metabolism, it is only more recently that we have begun to understand the complexities of SirT1 signaling. In addition to peroxisome proliferator-activated receptorgamma-coactivator 1 alpha, SirT1 has been found to regulate the activity and/or transcription of protein kinase B, mammalian target of rapamycin, forkhead box O 1 and 3a and myogenic determination factor, all of which are central players in the regulation of energy status in skeletal muscle, via actions on catabolic and anabolic signaling. Summary SirT1-mediated regulation of skeletal muscle metabolism (and indeed, whole body metabolism) likely occurs at numerous levels, from cell membrane receptors to transcription factors and histones. The end result of these regulatory actions of SirT1 is to maintain cellular homeostasis.