Matrisome alterations in obesity-Adipose tissue transcriptome study on monozygotic weight-discordant twins

Adipose tissue is a central regulator of metabolic health and its failure in obesity is a major cause of weight associated comorbidities, such as type 2 diabetes. Many extracellular matrix proteins, represented by matrisome, play a critical role in balancing adipose tissue health and dysfunction. Extracellular matrix components, produced by different cell types of adipose tissue, can modulate adipocyte function, tissue remodeling during expansion, angiogenesis, and inflammation and also form fibrotic lesions in the tissue. In this study, we investigated changes in matrisome of whole adipose tissue and adipocytes in human obesity. We investigated further the networks and biological pathways of the genes related to the changes and their association to development of metabolic dysfunction linked to type 2 diabetes. We used transcriptome data and clinical metabolic parameters from a rare weight-discordant MZ twin cohort. The Heavy-Lean differential matrisome gene expression (Dmatrisome) and differential metabolic parameters reflect changes in adipose tissue upon weight gain and changes in whole body glucose, insulin metabolism, as well as lipid status. We report that obesity Dmatrisome shows high specificity with 130 and 71 of the 1068 matrisome genes showing altered expression in the adipose tissue and adipocytes of heavier co-twin, respectively. The Dmatrisome differs considerably between adipose tissue vs adipocytes which reflects inflammation of hypertrophic adipocytes and the remodeling activity of the rest of the tissue resident cells. The obesity Dmatrisome is discussed extensively in the light of existing evidence and novel significant associations to obesity are reported to matrisome genes; cathepsin A, cathepsin O, FAM20B and N-glycanase1.(c) 2022 Elsevier B.V. All rights reserved.

Automated summary

This study investigates changes in the matrisome of adipose tissue and adipocytes in human obesity and explores their association with metabolic dysfunction related to type 2 diabetes. The findings reveal the specificity of obesity Dmatrisome, with 130 matrisome genes showing altered expression in adipose tissue and 71 genes in adipocytes. The Dmatrisome in obesity reflects inflammation in hypertrophic adipocytes and remodeling activity in the rest of the tissue resident cells. Additionally, significant associations of novel matrisome genes with obesity are reported.