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

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

doi:10.1016/j.xcrm.2021.100226

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

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 RissanenJaakko Kaprio, Evan G. Williams, Nicola Zamboni, Adil Mardinoglu, Päivi Pajukanta, Kirsi H. Pietiläinen

^*Corresponding author for this work

Centre for Host Microbiome Interactions

Research output: Contribution to journal › Article › peer-review

38 Citations (Scopus)

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.

Original language	English
Article number	100226
Journal	Cell Reports Medicine
Volume	2
Issue number	4
DOIs	https://doi.org/10.1016/j.xcrm.2021.100226
Publication status	Published - 20 Apr 2021

Keywords

adipose tissue
genome-scale metabolic models
metabolomics
multiomics
obesity
proteomics
skeletal muscle
transcriptomics
twins

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

Access to Document

10.1016/j.xcrm.2021.100226

Cite this

van der Kolk, B. W., 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, P. H., Tukiainen, T., Lundbom, N., ... Pietiläinen, K. H. (2021). Molecular pathways behind acquired obesity: Adipose tissue and skeletal muscle multiomics in monozygotic twin pairs discordant for BMI. Cell Reports Medicine, 2(4), Article 100226. https://doi.org/10.1016/j.xcrm.2021.100226

@article{db6ec12cf1b742698138341ef4fb52ee,

title = "Molecular pathways behind acquired obesity: Adipose tissue and skeletal muscle multiomics in monozygotic twin pairs discordant for BMI",

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.",

keywords = "adipose tissue, genome-scale metabolic models, metabolomics, multiomics, obesity, proteomics, skeletal muscle, transcriptomics, twins",

author = "{van der Kolk}, {Birgitta W.} and Sina Saari and Alen Lovric and Muhammad Arif and Marcus Alvarez and Arthur Ko and Zong Miao and Navid Sahebekhtiari and Maheswary Muniandy and Sini Heinonen and Ali Oghabian and Riikka Jokinen and Sakari Jukarainen and Antti Hakkarainen and Jesper Lundbom and Juho Kuula and Groop, {Per Henrik} and Taru Tukiainen and Nina Lundbom and Aila Rissanen and Jaakko Kaprio and Williams, {Evan G.} and Nicola Zamboni and Adil Mardinoglu and P{\"a}ivi Pajukanta and Pietil{\"a}inen, {Kirsi H.}",

note = "Funding Information: We thank the twin pairs for invaluable contributions to this study. The Obesity Research Unit team and the staff at the Finnish Twin Cohort Study are acknowledged for assistance with data collection. K.H.P. was funded by the Academy of Finland ( 314383 and 266286 ), the Academy of Finland Center of Excellence in Research on Mitochondria, Metabolism and Disease (FinMIT; 272376 ), the Finnish Medical Foundation , the Gyllenberg Foundation , the Novo Nordisk Foundation ( NNF17OC0027232 and NNF10OC1013354 ), the Finnish Diabetes Research Foundation , the Finnish Foundation for Cardiovascular Research , Government Research Funds , the University of Helsinki , and Helsinki University Hospital . B.W.v.d.K. was supported by the Finnish Diabetes Research Foundation . P.P. was supported by the National Institutes of Health (NIH; HL-095056 , HL-28481 , and U01 DK105561 ). M.A. was supported by the HHMI Gilliam Fellowship and NIH ( T32HG002536 ). A.K. was supported by the American Heart Association ( 19CDA34760186 ). J.K. was supported by the Academy of Finland ( 265240 , 263278 , 308248 , and 312073 ). N.Z. was supported by the Strategic Focal Area “Personalized Health and Related Technologies” (PHRT) of the ETH Domain . Z.M. was supported by the American Heart Association ( 19PRE34430112 ). Publisher Copyright: {\textcopyright} 2021 The Authors Copyright: Copyright 2021 Elsevier B.V., All rights reserved.",

year = "2021",

month = apr,

day = "20",

doi = "10.1016/j.xcrm.2021.100226",

language = "English",

volume = "2",

journal = "Cell Reports Medicine",

issn = "2666-3791",

publisher = "Cell Press",

number = "4",

}

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 2021, 'Molecular pathways behind acquired obesity: Adipose tissue and skeletal muscle multiomics in monozygotic twin pairs discordant for BMI', Cell Reports Medicine, vol. 2, no. 4, 100226. https://doi.org/10.1016/j.xcrm.2021.100226

TY - JOUR

T1 - Molecular pathways behind acquired obesity

T2 - Adipose tissue and skeletal muscle multiomics in monozygotic twin pairs discordant for BMI

AU - van der Kolk, Birgitta W.

AU - Saari, Sina

AU - Lovric, Alen

AU - Arif, Muhammad

AU - Alvarez, Marcus

AU - Ko, Arthur

AU - Miao, Zong

AU - Sahebekhtiari, Navid

AU - Muniandy, Maheswary

AU - Heinonen, Sini

AU - Oghabian, Ali

AU - Jokinen, Riikka

AU - Jukarainen, Sakari

AU - Hakkarainen, Antti

AU - Lundbom, Jesper

AU - Kuula, Juho

AU - Groop, Per Henrik

AU - Tukiainen, Taru

AU - Lundbom, Nina

AU - Rissanen, Aila

AU - Kaprio, Jaakko

AU - Williams, Evan G.

AU - Zamboni, Nicola

AU - Mardinoglu, Adil

AU - Pajukanta, Päivi

AU - Pietiläinen, Kirsi H.

N1 - Funding Information: We thank the twin pairs for invaluable contributions to this study. The Obesity Research Unit team and the staff at the Finnish Twin Cohort Study are acknowledged for assistance with data collection. K.H.P. was funded by the Academy of Finland ( 314383 and 266286 ), the Academy of Finland Center of Excellence in Research on Mitochondria, Metabolism and Disease (FinMIT; 272376 ), the Finnish Medical Foundation , the Gyllenberg Foundation , the Novo Nordisk Foundation ( NNF17OC0027232 and NNF10OC1013354 ), the Finnish Diabetes Research Foundation , the Finnish Foundation for Cardiovascular Research , Government Research Funds , the University of Helsinki , and Helsinki University Hospital . B.W.v.d.K. was supported by the Finnish Diabetes Research Foundation . P.P. was supported by the National Institutes of Health (NIH; HL-095056 , HL-28481 , and U01 DK105561 ). M.A. was supported by the HHMI Gilliam Fellowship and NIH ( T32HG002536 ). A.K. was supported by the American Heart Association ( 19CDA34760186 ). J.K. was supported by the Academy of Finland ( 265240 , 263278 , 308248 , and 312073 ). N.Z. was supported by the Strategic Focal Area “Personalized Health and Related Technologies” (PHRT) of the ETH Domain . Z.M. was supported by the American Heart Association ( 19PRE34430112 ). Publisher Copyright: © 2021 The Authors Copyright: Copyright 2021 Elsevier B.V., All rights reserved.

PY - 2021/4/20

Y1 - 2021/4/20

N2 - 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.

AB - 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.

KW - adipose tissue

KW - genome-scale metabolic models

KW - metabolomics

KW - multiomics

KW - obesity

KW - proteomics

KW - skeletal muscle

KW - transcriptomics

KW - twins

UR - http://www.scopus.com/inward/record.url?scp=85105035301&partnerID=8YFLogxK

U2 - 10.1016/j.xcrm.2021.100226

DO - 10.1016/j.xcrm.2021.100226

M3 - Article

AN - SCOPUS:85105035301

SN - 2666-3791

VL - 2

JO - Cell Reports Medicine

JF - Cell Reports Medicine

IS - 4

M1 - 100226

ER -

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

Abstract

Keywords

UN SDGs

Access to Document

Other files and links

Fingerprint

Cite this