The University of Sheffield, Sheffield, UK.
The University of Liverpool, Liverpool, UK.
J Cachexia Sarcopenia Muscle. 2022 Feb;13(1):68-85. doi: 10.1002/jcsm.12878. Epub 2022 Jan 4.
Sarcopenic obesity is a distinct condition of sarcopenia in the context of obesity, with the cumulative health risks of both phenotypes. Differential expression of microRNAs (miRNAs) has been reported separately in people with obesity and sarcopenia and may play a role in the pathogenesis of sarcopenic obesity. However, this has not been explored to date. This study aimed to identify differentially expressed miRNAs reported in serum, plasma, and skeletal muscle of people with obesity and sarcopenia and whether there are any commonalities between these conditions. We performed a systematic review on Embase and MEDLINE (PROSPERO, CRD42020224486) for differentially expressed miRNAs (fold change >1.5 or P-value <0.05) in (i) sarcopenia or frailty and (ii) obesity or metabolic syndrome. The functions and targets of miRNAs commonly changed in both conditions, in the same direction, were searched using PubMed. Following deduplication, 247 obesity and 42 sarcopenia studies were identified for full-text screening. Screening identified 36 obesity and 6 sarcopenia studies for final inclusion. A total of 351 miRNAs were identified in obesity and 157 in sarcopenia. Fifty-five miRNAs were identified in both obesity and sarcopenia-by sample type, 48 were found in plasma and one each in serum and skeletal muscle. Twenty-four miRNAs were identified from 10 of the included studies as commonly changed in the same direction (22 in plasma and one each in serum and skeletal muscle) in obesity and sarcopenia. The majority of miRNA-validated targets identified in the literature search were members of the phosphoinositide 3-kinase/protein kinase B and transforming growth factor-β signalling pathways. The most common targets identified were insulin-like growth factor 1 (miR-424-5p, miR-483-3p, and miR-18b-5p) and members of the SMAD family (miR-483-3p, miR-92a-3p, and miR-424-5p). The majority of commonly changed miRNAs were involved in protein homeostasis, mitochondrial dynamics, determination of muscle fibre type, insulin resistance, and adipogenesis. Twenty-four miRNAs were identified as commonly dysregulated in obesity and sarcopenia with functions and targets implicated in the pathogenesis of sarcopenic obesity. Given the adverse health outcomes associated with sarcopenic obesity, understanding the pathogenesis underlying this phenotype has the potential to lead to effective screening, monitoring, or treatment strategies. Further research is now required to confirm whether these miRNAs are differentially expressed in older adults with sarcopenic obesity.
肌少症合并肥胖是肥胖背景下肌少症的一种特殊情况,具有这两种表型的累积健康风险。微小 RNA(miRNA)的差异表达已分别在肥胖和肌少症患者中报道,可能在肌少症合并肥胖的发病机制中发挥作用。然而,迄今为止尚未对此进行探索。本研究旨在鉴定在肥胖和肌少症患者的血清、血浆和骨骼肌中报道的差异表达 miRNA,并确定这些条件之间是否存在任何共性。我们在 Embase 和 MEDLINE(PROSPERO、CRD42020224486)上进行了一项系统评价,以鉴定(i)肌少症或虚弱和(ii)肥胖或代谢综合征中差异表达的 miRNA(倍数变化>1.5 或 P 值<0.05)。使用 PubMed 搜索在两种情况下均以相同方向发生变化的 miRNA 的功能和靶标。在进行去重后,确定了 247 项肥胖和 42 项肌少症研究进行全文筛选。筛选确定了 36 项肥胖和 6 项肌少症研究进行最终纳入。在肥胖症中鉴定出 351 种 miRNA,在肌少症中鉴定出 157 种 miRNA。按样本类型,肥胖症中有 55 种 miRNA,血浆中有 48 种,血清中有 1 种,骨骼肌中有 1 种。在肥胖症和肌少症中以相同方向发生变化的 24 种 miRNA 是从 10 项纳入研究中确定的。在文献检索中鉴定的大多数 miRNA 验证靶标是磷酸肌醇 3-激酶/蛋白激酶 B 和转化生长因子-β信号通路的成员。鉴定出的最常见靶标是胰岛素样生长因子 1(miR-424-5p、miR-483-3p 和 miR-18b-5p)和 SMAD 家族成员(miR-483-3p、miR-92a-3p 和 miR-424-5p)。大多数共同改变的 miRNA 参与蛋白质稳态、线粒体动力学、肌肉纤维类型的确定、胰岛素抵抗和脂肪生成。在肥胖症和肌少症中,有 24 种 miRNA 被鉴定为共同失调,其功能和靶标与肌少症合并肥胖的发病机制有关。鉴于肌少症合并肥胖症与不良健康结局相关,了解该表型的发病机制有可能导致有效的筛查、监测或治疗策略。现在需要进一步的研究来确认这些 miRNA 是否在患有肌少症合并肥胖症的老年人中差异表达。
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