학술논문
Molecular pathways behind acquired obesity: Adipose tissue and skeletal muscle multiomics in monozygotic twin pairs discordant for BMI
Document Type
article
Author
Birgitta W. van der Kolk; Sina Saari; Alen Lovric; Muhammad Arif; Marcus Alvarez; Arthur Ko; Zong Miao; Navid Sahebekhtiari; Maheswary Muniandy; Sini Heinonen; Ali Oghabian; Riikka Jokinen; Sakari Jukarainen; Antti Hakkarainen; Jesper Lundbom; Juho Kuula; Per-Henrik Groop; Taru Tukiainen; Nina Lundbom; Aila Rissanen; Jaakko Kaprio; Evan G. Williams; Nicola Zamboni; Adil Mardinoglu; Päivi Pajukanta; Kirsi H. Pietiläinen
Source
Cell Reports Medicine, Vol 2, Iss 4, Pp 100226- (2021)
Subject
Language
English
ISSN
2666-3791
Abstract
Summary: 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.