Division of Endocrinology and Diabetes, Medanta The Medicity Hospital, Gurugram 122001, Haryana, India.
Department of Endocrinology and Nutrition, Virgen de la Victoria University Hospital, Instituto de Investigacion Biomedica de Malaga (IBIMA), Faculty of Medicine, University of Malaga, 29010 Malaga, Spain.
Ageing Res Rev. 2022 Sep;80:101696. doi: 10.1016/j.arr.2022.101696. Epub 2022 Jul 14.
In the last few decades, the loss of skeletal muscle mass and function, known as sarcopenia, has significantly increased in prevalence, becoming a major global public health concern. On the other hand, the prevalence of non-alcoholic fatty liver disease (NAFLD) has also reached pandemic proportions, constituting the leading cause of hepatic fibrosis worldwide. Remarkably, while sarcopenia and NAFLD-related fibrosis are independently associated with all-cause mortality, the combination of both conditions entails a greater risk for all-cause and cardiac-specific mortality. Interestingly, both sarcopenia and NAFLD-related fibrosis share common pathophysiological pathways, including insulin resistance, chronic inflammation, hyperammonemia, alterations in the regulation of myokines, sex hormones and growth hormone/insulin-like growth factor-1 signaling, which may explain reciprocal connections between these two disorders. Additional contributing factors, such as the gut microbiome, may also play a role in this relationship. In skeletal muscle, phosphatidylinositol 3-kinase/Akt and myostatin signaling are the central anabolic and catabolic pathways, respectively, and the imbalance between them can lead to muscle wasting in patients with NAFLD-related fibrosis. In this review, we summarize the bidirectional influence between NAFLD-related fibrosis and sarcopenia, highlighting the main potential mechanisms involved in this complex crosstalk, and we discuss the synergistic effects of both conditions in overall and cardiovascular mortality.
在过去的几十年中，骨骼肌质量和功能的丧失，即肌肉减少症，其患病率显著增加，已成为一个主要的全球公共卫生关注点。另一方面，非酒精性脂肪性肝病 (NAFLD) 的患病率也已达到流行程度，成为全球肝纤维化的主要原因。值得注意的是，虽然肌肉减少症和与 NAFLD 相关的纤维化都与全因死亡率独立相关，但这两种情况的组合会导致全因和心脏特异性死亡率的风险更高。有趣的是，肌肉减少症和与 NAFLD 相关的纤维化具有共同的病理生理途径，包括胰岛素抵抗、慢性炎症、高血氨、肌因子、性激素和生长激素/胰岛素样生长因子-1 信号转导的调节改变，这可能解释了这两种疾病之间的相互联系。其他促成因素，如肠道微生物组，也可能在这种关系中发挥作用。在骨骼肌中，磷脂酰肌醇 3-激酶/ Akt 和肌肉生长抑制素信号分别是主要的合成代谢和分解代谢途径，它们之间的失衡可能导致与 NAFLD 相关的纤维化患者出现肌肉消耗。在这篇综述中，我们总结了与 NAFLD 相关的纤维化和肌肉减少症之间的双向影响，强调了这种复杂串扰中涉及的主要潜在机制，并讨论了这两种情况对全因和心血管死亡率的协同作用。
