Molecular Pathways Behind Acquired Obesity: Adipose Tissue and Skeletal Muscle Multiomics in Monozygotic Twin Pairs Discordant for BMI

Overview

Journal Cell Rep Med

Publisher Cell Press

Specialties Biology
General Medicine

Date 2021 May 5

PMID 33948567

Citations 30

Authors

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

Paivi Pajukanta

Kirsi H Pietilainen

Affiliations

Soon will be listed here.

Abstract

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.

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