Abstract
Background
Obesity is a complex, multifactorial disease associated with substantial morbidity and mortality worldwide. Although it is frequently assessed using BMI, many epidemiological studies have shown links between body fat distribution and obesity-related outcomes. This study examined the relationships between body fat distribution and metabolic syndrome traits using Mendelian Randomization (MR).
Methods/findings
Genetic variants associated with visceral adipose tissue (VAT), abdominal subcutaneous adipose tissue (ASAT), and gluteofemoral adipose tissue (GFAT), as well as their relative ratios, were identified from a genome wide association study (GWAS) performed with the United Kingdom BioBank. GWAS summary statistics for traits and outcomes related to metabolic syndrome were obtained from the IEU Open GWAS Project. Two-sample MR and BMI-controlled multivariable MR (MVMR) were performed to examine relationships between each body fat measure and ratio with the outcomes. Increases in absolute GFAT were associated with a protective cardiometabolic profile, including lower low density lipoprotein cholesterol (β: -0.19, [95% CI: -0.28, -0.10], p < 0.001), higher high density lipoprotein cholesterol (β: 0.23, [95% CI: 0.03, 0.43], p = 0.025), lower triglycerides (β: -0.28, [95% CI: -0.45, -0.10], p = 0.0021), and decreased systolic (β: -1.65, [95% CI: -2.69, -0.61], p = 0.0019) and diastolic blood pressures (β: -0.95, [95% CI: -1.65, -0.25], p = 0.0075). These relationships were largely maintained in BMI-controlled MVMR analyses. Decreases in relative GFAT were linked with a worse cardiometabolic profile, with higher levels of detrimental lipids and increases in systolic and diastolic blood pressures.
Conclusion
A MR analysis of ASAT, GFAT, and VAT depots and their relative ratios with metabolic syndrome related traits and outcomes revealed that increased absolute and relative GFAT were associated with a favorable cardiometabolic profile independently of BMI. These associations highlight the importance of body fat distribution in obesity and more precise means to categorize obesity beyond BMI.
Funder
National Center for Advancing Translational Sciences of the National Institutes of Health
American Heart Association
National Institutes of Health
Institute for Translational Medicine and Therapeutics of the Perelman School of Medicine, University of Pennsylvania
National Heart, Lung, and Blood Institute
Measey Foundation
Doris Duke Charitable Foundation
Perelman School of Medicine, University of Pennsylvania
Publisher
Public Library of Science (PLoS)
Reference55 articles.
1. The epidemiology of obesity;YC Chooi;Metabolism,2019
2. Obesity and diabetes: An update;S Verma;Diabetes & Metabolic Syndrome: Clinical Research & Reviews,2017
3. Obesity and Cardiovascular Disease: A Scientific Statement From the American Heart Association;TM Powell-Wiley;Circulation,2021
4. Body Fatness and Cancer—Viewpoint of the IARC Working Group;B Lauby-Secretan;New England Journal of Medicine,2016
5. Obesity and Kidney Disease;CP Kovesdy;Can J Kidney Health Dis,2017