Gene expression profile of subcutaneous adipose tissue in BMI-discordant monozygotic twin pairs unravels molecular and clinical changes associated with sub-types of obesity

Abstract

BACKGROUND: Subcutaneous adipose tissue (SAT) undergoes major changes in obesity, but little is known about the wholegenome scale patterns of these changes or about their variation between different obesity sub-groups. We sought to compare how transcriptomics profiles in SAT differ between monozygotic (MZ) co-twins who are discordant for body mass index (BMI), whether the profiles vary between twin pairs and whether the variation can be linked to clinical characteristics. METHODS: We analysed the transcriptomics (Affymetrix U133 Plus 2.0) patterns of SAT in young MZ twin pairs (n = 26, intra-pair difference in BMI 43 kg m − 2 , aged 23-36), from 10 birth cohorts of adult Finnish twins. The clinical data included measurements of body composition, insulin resistance, lipids and adipokines. RESULTS: We found 2108 genes differentially expressed (false discovery rate (FDR)o 0.05) in SAT of the BMI-discordant pairs. Pathway analyses of these genes revealed a significant downregulation of mitochondrial oxidative pathways (P o 0.05) and upregulation of inflammation pathways (P o 0.05). Hierarchical clustering of heavy/lean twin ratios, representing effects of acquired obesity in the transcriptomics data, revealed three sub-groups with different molecular profiles (FDR o 0.05). Analyses comparing these sub-groups showed that, in the heavy co-twins, downregulation of the mitochondrial pathways, especially that of branched chain amino acid degradation was more evident in two clusters while and upregulation of the inflammatory response was most evident in the last, presumably the unhealthiest cluster. High-fasting insulin levels and large adipocyte diameter were the predominant clinical characteristic of the heavy co-twins in this cluster (Bonferroni-adjusted P o 0.05). CONCLUSIONS: This is the first study in BMI-discordant MZ twin pairs reporting sub-types of obesity based on both SAT gene expression profiles and clinical traits. We conclude that a decrease in mitochondrial BCAA degradation and an increase in inflammation in SAT co-occur and associate with hyperinsulinemia and large adipocyte size in unhealthy obesity.

Gene Co-expression Networks Are Associated with Obesity-Related Traits in Kidney Transplant Recipients

“…Other genes within the magenta module play a role in metabolic functions and obesity including genes that code for lipase (LIPA), phospholipid transfer protein (PTLP), (28) and lipid metabolism (e.g., LPIN1) (29). This suggests that there is a relationship between metabolism, immune response, inflammatory-related genes, and body-fat in kidney transplant The findings of the current study are supported by previous studies which have found immunological, inflammatory, and metabolic genetic drivers are influential in the determination of obesity (32)(33)(34).…”

“…al used adipose tissue (subcutaneous) to study clinical changes associated with obesity; The study found that the heavier twin in BMI-discordant monozygotic twin pairs displayed an upregulation of inflammation and other immunological pathways/genes (e.g. IFI30 and CCL18) (32). Other studies have used blood samples to examine differential gene expression and weighted gene co-expression network analysis from a cohort of monozygotic twins (27).…”

Obesity and eating behavior from the perspective of twin and genetic research

“…Additionally, since gene-expression, affected by methylations and other factors, changes over aging, it is convenient that co-twins have always the same age. Epigenetic research is outside the scope of this review, but this approach has been successfully used to analyze, for example, the gene expression of fat tissue in twins discordant for BMI (Muniandy et al, 2017).…”

Gene Co-expression Networks Are Associated with Obesity-Related Traits in Kidney Transplant Recipients

“…Other studies have found immunological and inflammatory genetic drivers as influential in the determination of BMI (25)(26)(27). One such study analyzed differential gene expression data using subcutaneous adipose tissue samples from BMI-discordant monozygotic twin pairs.…”

“…Pathway analysis among this cohort revealed upregulation of inflammation and other immunological pathway signaling in the heavy co-twins. In addition, immune-related genes such as IFI30 and CCL18 were upregulated in the heavy co-twins (25). Other studies conducted gene expression profiling using whole blood samples.…”