Obesity Research Unit, Research Program for Clinical and Molecular Metabolism, Faculty of Medicine, University of Helsinki, Helsinki, Finland.
Science for Life Laboratory, KTH-Royal Institute of Technology, Stockholm, Sweden.
Cell Rep Med. 2021 Mar 30;2(4):100226. doi: 10.1016/j.xcrm.2021.100226. eCollection 2021 Apr 20.
Tissue-specific mechanisms prompting obesity-related development complications in humans remain unclear. We apply multiomics analyses of subcutaneous adipose tissue and skeletal muscle to examine the effects of acquired obesity among 49 BMI-discordant monozygotic twin pairs. Overall, adipose tissue appears to be more affected by excess body weight than skeletal muscle. In heavier co-twins, we observe a transcriptional pattern of downregulated mitochondrial pathways in both tissues and upregulated inflammatory pathways in adipose tissue. In adipose tissue, heavier co-twins exhibit lower creatine levels; in skeletal muscle, glycolysis- and redox stress-related protein and metabolite levels remain higher. Furthermore, metabolomics analyses in both tissues reveal that several proinflammatory lipids are higher and six of the same lipid derivatives are lower in acquired obesity. Finally, in adipose tissue, but not in skeletal muscle, mitochondrial downregulation and upregulated inflammation are associated with a fatty liver, insulin resistance, and dyslipidemia, suggesting that adipose tissue dominates in acquired obesity.
组织特异性机制促使人类肥胖相关并发症的发展仍不清楚。我们应用皮下脂肪组织和骨骼肌的多组学分析来研究 49 对 BMI 不一致的同卵双胞胎中获得性肥胖的影响。总的来说，脂肪组织似乎比骨骼肌更容易受到超重的影响。在更重的同卵双胞胎中，我们观察到两种组织中线粒体途径下调和脂肪组织中炎症途径上调的转录模式。在脂肪组织中，更重的同卵双胞胎表现出较低的肌酸水平；在骨骼肌中，糖酵解和氧化还原应激相关蛋白和代谢物水平仍然较高。此外，两种组织的代谢组学分析表明，几种促炎脂质在获得性肥胖中较高，六种相同的脂质衍生物较低。最后，在脂肪组织中，但不是在骨骼肌中，线粒体下调和炎症上调与脂肪肝、胰岛素抵抗和血脂异常有关，这表明脂肪组织在获得性肥胖中占主导地位。
