Abstract
Skeletal muscle comprises 30–40% of the total body mass and plays a central role in energy homeostasis in the body. The deregulation of energy homeostasis is a common underlying characteristic of metabolic syndrome. Over the past decades, peroxisome proliferator-activated receptors (PPARs) have been shown to play critical regulatory roles in skeletal muscle. The three family members of PPAR have overlapping roles that contribute to the myriad of processes in skeletal muscle. This review aims to provide an overview of the functions of different PPAR members in energy homeostasis as well as during skeletal muscle metabolic disorders, with a particular focus on human and relevant mouse model studies.
Highlights
Skeletal muscle is the largest metabolic organ in the human body, and it contributes ~40% of the total human body mass in healthy non-obese adults
The deregulation of skeletal muscle energy homeostasis plays a major role in the pathogenesis of peripheral insulin resistance and type 2 diabetes mellitus (T2DM)
peroxisome proliferator-activated receptors (PPARs) are ligand-activated transcription factors that belong to the nuclear hormone receptor superfamily, and they are activated by a variety of synthetic ligands and endogenous ligands, such as the naturally occurring free fatty acid (FFA) and their metabolites, arachidonic acid and eicosanoids
Summary
Skeletal muscle is the largest metabolic organ in the human body, and it contributes ~40% of the total human body mass in healthy non-obese adults. The type I fibers are rich in myoglobin, surrounded by many capillaries, and contain relatively abundant intracellular lipid levels for oxidative metabolism. These characteristics support long-duration contractile activities, such as walking and postural stabilization. The deregulation of skeletal muscle energy homeostasis plays a major role in the pathogenesis of peripheral insulin resistance and type 2 diabetes mellitus (T2DM). The deregulation of the metabolic homeostasis in skeletal muscle causes muscle fiber type switching, from the slow-twitch to fast-twitch, as the disease worsens over time [7]. The peroxisome proliferator-activated receptors (PPARs) have emerged as the master regulators of both lipid and glucose homeostasis, and are considered as valuable pharmaceutical targets for treating metabolic dysfunctions and T2DM. We will focus on the metabolic regulatory roles of PPARs in the skeletal muscle during healthy and diseased states, primarily with studies that have used human and mouse models
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