Differences in Muscle and Adipose Tissue Gene Expression and Cardio-Metabolic Risk Factors in the Members of Physical Activity Discordant Twin Pairs

Abstract

High physical activity/aerobic fitness predicts low morbidity and mortality. Our aim was to identify the most up-regulated gene sets related to long-term physical activity vs. inactivity in skeletal muscle and adipose tissues and to obtain further information about their link with cardio-metabolic risk factors. We studied ten same-sex twin pairs (age range 50–74 years) who had been discordant for leisure-time physical activity for 30 years. The examinations included biopsies from m. vastus lateralis and abdominal subcutaneous adipose tissue. RNA was analyzed with the genome-wide Illumina Human WG-6 v3.0 Expression BeadChip. For pathway analysis we used Gene Set Enrichment Analysis utilizing active vs. inactive co-twin gene expression ratios. Our findings showed that among the physically active members of twin pairs, as compared to their inactive co-twins, gene expression in the muscle tissue samples was chronically up-regulated for the central pathways related to energy metabolism, including oxidative phosphorylation, lipid metabolism and supportive metabolic pathways. Up-regulation of these pathways was associated in particular with aerobic fitness and high HDL cholesterol levels. In fat tissue we found physical activity-associated increases in the expression of polyunsaturated fatty acid metabolism and branched-chain amino acid degradation gene sets both of which associated with decreased ‘high-risk’ ectopic body fat and plasma glucose levels. Consistent with other findings, plasma lipidomics analysis showed up-regulation of the triacylglycerols containing the polyunsaturated fatty acids. Our findings identified skeletal muscle and fat tissue pathways which are associated with the long-term physical activity and reduced cardio-metabolic disease risk, including increased aerobic fitness. In particular, improved skeletal muscle oxidative energy and lipid metabolism as well as changes in adipocyte function and redistribution of body fat are associated with reduced cardio-metabolic risk.

Causes and consequences of obesity: the contribution of recent twin studies

“…52 A similar finding in a study of the Finnish same-sex twins discordant for physical activity for almost 30 years showed a clear downregulation of BCAA catabolism in both adipose and skeletal muscle tissue among the less active co-twins. 53 Together these findings strengthen the view that mitochondrial dysfunction and specifically BCAA catabolism has a key role in the development of obesity-related insulin resistance and that exercise may counteract these effects.…”

Long-term Leisure-time Physical Activity and Serum Metabolome

“…20 In addition, 10 twin pairs free of diabetes mellitus and coronary heart disease volunteered another laboratory visit to give muscle (vastus lateralis) and abdominal subcutaneous adipose tissue needle biopsy samples for gene expression analyses after an overnight fast. 21 After clustering of genes expressed differentially between active and inactive co-twins into functional groups, the leading-edge genes (ie, genes contributing to the enrichment scores of the Gene Set Enrichment Analysis) 22 were used to calculate expression centroids for those gene sets that were most upregulated among active compared with inactive co-twins. 21 Before both their laboratory visits, the twins were advised not to exercise vigorously (except for walking and other daily chores) during the 2 days before the visits.…”

“…21 After clustering of genes expressed differentially between active and inactive co-twins into functional groups, the leading-edge genes (ie, genes contributing to the enrichment scores of the Gene Set Enrichment Analysis) 22 were used to calculate expression centroids for those gene sets that were most upregulated among active compared with inactive co-twins. 21 Before both their laboratory visits, the twins were advised not to exercise vigorously (except for walking and other daily chores) during the 2 days before the visits. …”

“…21 HDL cholesterol may have as-yet unknown roles in oxidative metabolism such as its role as (mi)RNA transporter. 39 In addition, a finding consistently pointing toward lower cardiovascular risk among the physically active was their lower ratio of apolipoprotein B to A1.…”

Health-Related Findings Among Twin Pairs Discordant for Leisure-Time Physical Activity for 32 Years: The TWINACTIVE Study Synopsis

“…In addition, from healthy volunteers (three MZ and seven DZ pairs from the TWINACTIVE participants), we took muscle and subcutaneous adipose tissue samples a few weeks after the first laboratory visit for gene expression arrays (Leskinen et al, 2010). The authors declare that all procedures that contributed to this work complied with the ethical standards of the relevant national and institutional committees on human experimentation and with the Helsinki Declaration of 1975, as revised in 2008.…”