Department of Medical Sciences, Division of Gastroenterology and Hepatology, A.O. Città della Salute e della Scienza di Torino, University of Turin, Turin, Italy.
Front Endocrinol (Lausanne). 2021 Nov 10;12:716533. doi: 10.3389/fendo.2021.716533. eCollection 2021.
Sarcopenia is a common muscular affection among elderly individuals. More recently, it has been recognized as the skeletal muscle (SM) expression of the metabolic syndrome. The prevalence of sarcopenia is increasing along with visceral obesity, to which it is tightly associated. Nonetheless, it is a still underreported entity by clinicians, despite the worsening in disease burden and reduced patient quality of life. Recognition of sarcopenia is clinically challenging, and variability in study populations and diagnostic methods across the clinical studies makes it hard to reach a strong evidence. Impaired insulin activity in SM is responsible for the altered molecular pathways and clinical manifestations of sarcopenia, which is morphologically expressed by myosteatosis. Lipotoxicity, oxidative stress and adipose tissue-derived inflammation lead to both alterations in glucose disposal and protein synthesis in SM, with raising insulin resistance (IR) and SM atrophy. In particular, hyperleptinemia and leptin resistance interfere directly with SM activity, but also with the release of Growth Hormone from the hypohysis, leading to a lack in its anabolic effect on SM. Moreover, sarcopenia is independently associated to liver fibrosis in Non-Alcoholic Fatty Liver Disease (NAFLD), which in turn worsens SM functionality through the secretion of proinflammatory heptokines. The cross-talk between the liver and SM in the IR setting is of crucial relevance, given the high prevalence of NAFLD and the reciprocal impact of insulin-sensitive tissues on the overall disease burden. Along with the efforts of non-invasive diagnostic approaches, irisin and myostatin are two myokines currently evaluated as potential biomarkers for diagnosis and prognostication. Decreased irisin levels seem to be potentially associated to sarcopenia, whereas increased myostatin has shown to negatively impact on sarcopenia in pre-clinical studies. Gene variants in irisin have been explored with regard to the impact on the liver disease phenotype, with conflicting results. The gut-muscle axis has gain relevance with the evidence that insulin resistance-derived gut dysbiosis is responsible for increased endotoxemia and reduction in short-chain free fatty acids, directly affecting and predisposing to sarcopenia. Based on the current evidence, more efforts are needed to increase awareness and improve the management of sarcopenic patients.
肌少症是老年人常见的肌肉疾病。最近，它被认为是代谢综合征的骨骼肌（SM）表现。随着内脏肥胖的增加，肌少症的患病率也在增加，两者密切相关。尽管疾病负担加重和患者生活质量下降，但临床医生对肌少症的认识仍然不足。SM 中胰岛素活性的改变导致了肌少症的分子途径和临床表现的改变，其形态学表现为肌脂肪病。脂肪毒性、氧化应激和脂肪组织来源的炎症导致 SM 中葡萄糖摄取和蛋白质合成的改变，从而导致胰岛素抵抗（IR）和 SM 萎缩。特别是，高瘦素血症和瘦素抵抗直接干扰 SM 活性，也干扰垂体释放生长激素，导致其对 SM 的合成代谢作用缺失。此外，肌少症与非酒精性脂肪性肝病（NAFLD）中的肝纤维化独立相关，后者通过分泌前炎症细胞因子进一步加重 SM 功能障碍。IR 状态下肝脏和 SM 之间的相互作用至关重要，因为 NAFLD 的患病率很高，而胰岛素敏感组织对整体疾病负担也有相互影响。除了努力开发非侵入性诊断方法外，鸢尾素和肌肉生长抑制素这两种肌肽目前被评估为诊断和预后的潜在生物标志物。鸢尾素水平的降低似乎与肌少症有潜在关联，而前临床研究表明，肌肉生长抑制素的增加对肌少症有负面影响。关于鸢尾素基因变异对肝病表型的影响进行了探讨，但结果存在争议。肠道-肌肉轴的重要性在于，IR 衍生的肠道菌群失调导致内毒素血症增加和短链游离脂肪酸减少，这直接影响并导致肌少症。基于目前的证据，需要进一步努力提高对肌少症患者的认识并改善其管理。
