[en] 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.
Disciplines :
Biochemistry, biophysics & molecular biology
Author, co-author :
van der Kolk, Birgitta W.
Saari, Sina
Lovric, Alen
Arif, Muhammad
Alvarez, Marcus
Ko, Arthur
Miao, Zong
Sahebekhtiari, Navid
Muniandy, Maheswary
Heinonen, Sini
Oghabian, Ali
Jokinen, Riikka
Jukarainen, Sakari
Hakkarainen, Antti
Lundbom, Jesper
Kuula, Juho
Groop, Per-Henrik
Tukiainen, Taru
Lundbom, Nina
Rissanen, Aila
Kaprio, Jaakko
Williams, Evan ; University of Luxembourg > Luxembourg Centre for Systems Biomedicine (LCSB) > Gene Expression and Metabolism