Abstract
SummaryTissue-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.
Highlights
Obesity, a major public health burden, has increased globally, doubling in prevalence in 70 countries between 1980 and 2015.1 Obesity predisposes individuals to a range of complex metabolic diseases, including type 2 diabetes mellitus (T2DM), cardiovascular diseases, and some cancers.[2]
We detected no differences in total cholesterol, lowdensity lipoprotein (LDL) cholesterol, C-reactive protein (CRP), or physical activity levels between the heavier and leaner co-twins
More transcripts were altered in adipose tissue than in skeletal muscle To understand the biological effect of the acquired excess body weight, we first compared the adipose tissue and skeletal muscle transcriptomes among co-twins
Summary
A major public health burden, has increased globally, doubling in prevalence in 70 countries between 1980 and 2015.1 Obesity predisposes individuals to a range of complex metabolic diseases, including type 2 diabetes mellitus (T2DM), cardiovascular diseases, and some cancers.[2].
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