Dataset Information

ACE2 expression in adipose tissue is associated with cardio-metabolic risk factors and cell type composition-implications for COVID-19.

ABSTRACT:

Background

COVID-19 severity varies widely. Although some demographic and cardio-metabolic factors, including age and obesity, are associated with increasing risk of severe illness, the underlying mechanism(s) are uncertain.

Subjects/methods

In a meta-analysis of three independent studies of 1471 participants in total, we investigated phenotypic and genetic factors associated with subcutaneous adipose tissue expression of Angiotensin I Converting Enzyme 2 (ACE2), measured by RNA-Seq, which acts as a receptor for SARS-CoV-2 cellular entry.

Results

Lower adipose tissue ACE2 expression was associated with multiple adverse cardio-metabolic health indices, including type 2 diabetes (T2D) (P = 9.14 × 10^-6), obesity status (P = 4.81 × 10^-5), higher serum fasting insulin (P = 5.32 × 10^-4), BMI (P = 3.94 × 10^-4), and lower serum HDL levels (P = 1.92 × 10^-7). ACE2 expression was also associated with estimated proportions of cell types in adipose tissue: lower expression was associated with a lower proportion of microvascular endothelial cells (P = 4.25 × 10^-4) and higher proportion of macrophages (P = 2.74 × 10^-5). Despite an estimated heritability of 32%, we did not identify any proximal or distal expression quantitative trait loci (eQTLs) associated with adipose tissue ACE2 expression.

Conclusions

Our results demonstrate that individuals with cardio-metabolic features known to increase risk of severe COVID-19 have lower background ACE2 levels in this highly relevant tissue. Reduced adipose tissue ACE2 expression may contribute to the pathophysiology of cardio-metabolic diseases, as well as the associated increased risk of severe COVID-19.

SUBMITTER: El-Sayed Moustafa JS

PROVIDER: S-EPMC9119844 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Similar Datasets

Project description: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.

Project description:BackgroundObesity is one of the conditions that increases the risk of cardiovascular disease. Studies about obesity trajectory and cardio metabolic outcomes at adulthood are still scarce. Therefore, we aimed to assess the association between patterns of overweight over the life-course and cardio metabolic risk factors in young adults.MethodsIn 1982, the maternity hospitals in Pelotas were visited daily and those newborns whose family lived in the urban area of the city were identified (n = 5914), and have prospectively followed for several occasions. Weight and height were measured at every visit. BMI-for-age z-score was calculated using the WHO Child Growth Standards. Overweight and obesity were defined as a BMI greater than or equal to 25 kg/m2 and 30 kg/m2 respectively. This was the definition adopted for evaluations overweight and obesity at 30 years. The participants were divided into eight groups according to the presence of overweight or obesity in childhood, adolescence and adulthood. Blood pressure, random blood glucose, HDL cholesterol, LDL cholesterol triglycerides and fat mass were measured.ResultsFrom 2219 participants with anthropometric data in childhood, adolescence and adulthood, 25% never had been overweight, whereas 11.6% were overweight in the three periods. Random blood glucose, SBP and DBP were higher among those subjects who were always overweight/ obese or only overweight/obese during adolescence and adulthood. The participants who were never overweight/obese or only in childhood or adolescence had a lower cardiovascular risk profile (higher HDL cholesterol, lower blood pressure, lower random glucose, lower LDL cholesterol) at 30 years. Fat mass captured from 25 to 100% of the association of overweight and obesity trajectory with cardiometabolic risk factors.ConclusionsThe tracking of overweight/obesity is associated with an adverse cardio metabolic profile and this association is largely mediated by fat mass in adulthood.