Sarcopenic obesity or obese sarcopenia: A cross talk between age-associated adipose tissue and skeletal muscle inflammation as a main mechanism of the pathogenesis
Sarcopenic obesity or obese sarcopenia: A cross talk between age-associated adipose tissue and skeletal muscle inflammation as a main mechanism of the pathogenesis
复制标题
肌少性肥胖或肥胖性肌少症：年龄相关性脂肪组织与骨骼肌炎症之间的相互作用是其发病的主要机制
DOI：
10.1016/j.arr.2016.09.008
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发表时间：
2017-05-01
影响因子：
13.1
通讯作者：
Livshits, Gregory
中科院分区：
文献类型：
--
作者：
Kalinkovich, Alexander;Livshits, Gregory
肌肉减少症是一种与年龄相关的骨骼肌质量下降和功能退化，可能因肥胖而加剧，导致更高的残疾、虚弱、发病率和死亡率。在肌肉减少症和肥胖症的结合中，一些关键的年龄和肥胖介导的因素和途径可能加重肌肉减少症，称为肌肉减少性肥胖（sarcopenic obesity，SAB）。本文就其发病机制作一综述。在肥胖脂肪组织（AT）中，脂肪细胞经历肥大、增生和活化，导致促炎性巨噬细胞和其他免疫细胞的积累以及各种脂肪因子的失调产生，所述脂肪因子与衰老细胞和免疫细胞释放的细胞因子和趋化因子一起产生局部促炎性状态。此外，肥胖AT的特征在于过量产生和紊乱的储存脂质的能力，其在骨骼肌中异位积累。这些肌内脂质及其衍生物诱导线粒体功能障碍，其特征在于β-氧化能力受损和活性氧形成增加，提供脂毒性环境和胰岛素抵抗，以及一些促炎性肌因子的分泌增强，这些促炎性肌因子能够通过自分泌/旁分泌方式诱导肌肉功能障碍。反过来，通过内分泌方式，这些肌因子可能加剧AT炎症，也支持慢性低度全身性炎症（炎症），总体上建立了维持AT和骨骼肌炎症的有害恶性循环，从而触发和支持AT发展。在这种情况下，我们认为AT炎症比骨骼肌炎症更重要。因此，本质上，它将过程的向量从“少肌症->肥胖症”重定向到“肥胖症->少肌症”。因此，我们建议将这种情况定义为“肥胖性肌肉减少症”，以反映病理途径的方向。(C)© 2016 Elsevier B. V.版权所有。
Sarcopenia, an age-associated decline in skeletal muscle mass coupled with functional deterioration, may be exacerbated by obesity leading to higher disability, frailty, morbidity and mortality rates. In the combination of sarcopenia and obesity, the state called sarcopenic obesity (SOB), some key age and obesity-mediated factors and pathways may aggravate sarcopenia. This review will analyze the mechanisms underlying the pathogenesis of SOB. In obese adipose tissue (AT), adipocytes undergo hypertrophy, hyperplasia and activation resulted in accumulation of pro-inflammatory macrophages and other immune cells as well as dysregulated production of various adipokines that together with senescent cells and the immune cell-released cytokines and chemokines create a local pro-inflammatory status. In addition, obese AT is characterized by excessive production and disturbed capacity to store lipids, which accumulate ectopically in skeletal muscle. These intramuscular lipids and their derivatives induce mitochondria( dysfunction characterized by impaired beta-oxidation capacity and increased reactive oxygen species formation providing lipotoxic environment and insulin resistance as well as enhanced secretion of some pro-inflammatory myokines capable of inducing muscle dysfunction by auto/paracrine manner. In turn, by endocrine manner, these myokines may exacerbate AT inflammation and also support chronic low grade systemic inflammation (inflammaging), overall establishing a detrimental vicious circle maintaining AT and skeletal muscle inflammation, thus triggering and supporting SOB development. Under these circumstances, we believe that AT inflammation dominates over skeletal muscle inflammation. Thus, in essence, it redirects the vector of processes from "sarcopenia -> obesity" to "obesity -> sarcopenia". We therefore propose that this condition be defined as "obese sarcopenia", to reflect the direction of the pathological pathway. (C) 2016 Elsevier B.V. All rights reserved.