Molecular pathways behind acquired obesity: Adipose tissue and skeletal muscle multiomics in monozygotic twin pairs discordant for BMI.

van der Kolk BW, Saari S, Lovric A, Arif M, Alvarez M, Ko A, Miao Z, Sahebekhtiari N, Muniandy M, Heinonen S, Oghabian A, Jokinen R, Jukarainen S, Hakkarainen A, Lundbom J, Kuula J, Groop PH, Tukiainen T, Lundbom N, Rissanen A, Kaprio J, Williams EG, Zamboni N, Mardinoglu A, Pajukanta P, Pietiläinen KH

Cell Rep Med 2 (4) 100226 [2021-04-20; online 2021-03-30]

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.

Adil Mardinoglu

SciLifeLab Fellow

PubMed 33948567

DOI 10.1016/j.xcrm.2021.100226

Crossref 10.1016/j.xcrm.2021.100226

pmc: PMC8080113
pii: S2666-3791(21)00042-2

Publications 9.5.0