Department of Pharmaceutical Sciences, University of South Florida, 12901 Bruce B. Downs Blvd., Tampa, FL 33612, USA.
Department of Nutritional Sciences, University of Vienna, Althanstrasse 14, 1090 Vienna, Austria.
Int J Mol Sci. 2020 Oct 29;21(21):8056. doi: 10.3390/ijms21218056.
Skeletal muscle is a major metabolic organ that uses mostly glucose and lipids for energy production and has the capacity to remodel itself in response to exercise and fasting. Skeletal muscle wasting occurs in many diseases and during aging. Muscle wasting is often accompanied by chronic low-grade inflammation associated to inter- and intra-muscular fat deposition. During aging, muscle wasting is advanced due to increased movement disorders, as a result of restricted physical exercise, frailty, and the pain associated with arthritis. Muscle atrophy is characterized by increased protein degradation, where the ubiquitin-proteasomal and autophagy-lysosomal pathways, atrogenes, and growth factor signaling all play an important role. Peroxisome proliferator-activated receptors (PPARs) are members of the nuclear receptor family of transcription factors, which are activated by fatty acids and their derivatives. PPARs regulate genes that are involved in development, metabolism, inflammation, and many cellular processes in different organs. PPARs are also expressed in muscle and exert pleiotropic specialized responses upon activation by their ligands. There are three PPAR isotypes, viz., PPARα, -β/δ, and -γ. The expression of PPARα is high in tissues with effective fatty acid catabolism, including skeletal muscle. PPARβ/δ is expressed more ubiquitously and is the predominant isotype in skeletal muscle. It is involved in energy metabolism, mitochondrial biogenesis, and fiber-type switching. The expression of PPARγ is high in adipocytes, but it is also implicated in lipid deposition in muscle and other organs. Collectively, all three PPAR isotypes have a major impact on muscle homeostasis either directly or indirectly. Furthermore, reciprocal interactions have been found between PPARs and the gut microbiota along the gut-muscle axis in both health and disease. Herein, we review functions of PPARs in skeletal muscle and their interaction with the gut microbiota in the context of muscle wasting.
骨骼肌是一种主要的代谢器官，主要利用葡萄糖和脂质来产生能量，并具有响应运动和禁食进行自身重塑的能力。许多疾病和衰老过程中都会发生骨骼肌减少症。肌肉减少症通常伴随着慢性低度炎症，伴随着肌肉内和肌肉间脂肪沉积。随着年龄的增长，由于运动障碍增加、体力活动受限、虚弱以及关节炎相关疼痛，肌肉减少症会进一步加重。肌肉萎缩的特征是蛋白质降解增加，其中泛素蛋白酶体和自噬溶酶体途径、肌萎缩基因和生长因子信号转导都起着重要作用。过氧化物酶体增殖物激活受体 (PPARs) 是核受体转录因子家族的成员，它们被脂肪酸及其衍生物激活。PPARs 调节参与不同器官发育、代谢、炎症和许多细胞过程的基因。PPARs 也在肌肉中表达，并在其配体激活时发挥多效性的特殊反应。有三种 PPAR 同工型，即 PPARα、-β/δ 和 -γ。PPARα 在具有有效脂肪酸分解代谢的组织中表达较高，包括骨骼肌。PPARβ/δ 表达更广泛，是骨骼肌中的主要同工型。它参与能量代谢、线粒体生物发生和纤维型转换。PPARγ 在脂肪细胞中表达较高，但它也与肌肉和其他器官中的脂质沉积有关。总的来说，所有三种 PPAR 同工型都直接或间接地对肌肉稳态产生重大影响。此外，在健康和疾病状态下，已经发现 PPARs 与肠道微生物群之间存在沿肠道-肌肉轴的相互作用。本文综述了 PPARs 在骨骼肌中的功能及其与肌肉减少症背景下肠道微生物群的相互作用。
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