Histone deacetylase functions and therapeutic implications for adult skeletal muscle metabolism

Abstract

Skeletal muscle is a highly adaptive organ that sustains continuous metabolic changes in response to different functional demands. Healthy skeletal muscle can adjust fuel utilization to the intensity of muscle activity, the availability of nutrients and the intrinsic characteristics of muscle fibers. This property is defined as metabolic flexibility. Importantly, impaired metabolic flexibility has been associated with, and likely contributes to the onset and progression of numerous pathologies, including sarcopenia and type 2 diabetes. Numerous studies involving genetic and pharmacological manipulations of histone deacetylases (HDACs) in vitro and in vivo have elucidated their multiple functions in regulating adult skeletal muscle metabolism and adaptation. Here, we briefly review HDAC classification and skeletal muscle metabolism in physiological conditions and upon metabolic stimuli. We then discuss HDAC functions in regulating skeletal muscle metabolism at baseline and following exercise. Finally, we give an overview of the literature regarding the activity of HDACs in skeletal muscle aging and their potential as therapeutic targets for the treatment of insulin resistance.

Effects of Supplementing Growing–Finishing Crossbred Pigs with Glycerin, Vitamin C and Niacinamide on Carcass Characteristics and Meat Quality

“…Myofiber types also can influence the redness (a*) value of muscle [40,41]; these myofibers can be divided into oxidative types, including type I and IIa, which are red and rich in mitochondria, and into lipids, myoglobin and glycolytic type Iib, which are white and possess fewer mitochondria, lipids and myoglobin [42,43]. The supplementation of the diet of obese Zucker rats or growing pigs with niacin at 750 mg/kg induced type II myofiber to switch to type I muscle fiber, increasing the percentage of type I myofibers in the muscle [44,45].…”

Epitranscriptomics as a New Layer of Regulation of Gene Expression in Skeletal Muscle: Known Functions and Future Perspectives

“…SIRT1 enzymatic activity is deeply correlated with the differentiation of muscle fibers, energy homeostasis and muscle cell fate signaling. In addition to SIRT1-mediated effects on the transcription of key genes, among which is MyoD [178], SIRT1 is intimately linked to nutrient availability in muscle cells and controls energy metabolism [179]. Moreover, as an inhibitor of nuclear factor kappa-B DNA binding subunit (NF-KB) signaling, SIRT1 activation ameliorates muscle pathology in MD [180,181].…”

Targeting Epigenetic Regulators with HDAC and BET Inhibitors to Modulate Muscle Wasting

“…The inhibition of HDAC activity has resulted in improvements, for example, with AR-42 in C26-tumor-bearing mice [137] and with entinostat in cardiac complications in rodent cachexia [138]. In addition to the control of processes regulating muscle atrophy, HDACs can modify the expression of critical metabolic enzymes; a recent review highlights the most relevant metabolic pathways regulated by HDACs [139]. For example, class II HDACs induce gluconeogenic enzyme G6Pase expression [108], while also triggering their other downstream target FoxO, a transcription factor associated with muscle protein degradation and autophagy [140], providing another link between epigenetic regulation and metabolism for muscle atrophy.…”