Not All Obesity Is the Same: Scientists Find Genetic Answers

An international team of researchers led by Icahn School of Medicine at Mount Sinai and the University of Copenhagen in Denmark has pinpointed some of the reasons why obesity does not affect everyone in the same way. Their study, published today in Nature Medicine, identifies genetic differences that help explain why some people with obesity remain relatively healthy while others develop serious conditions like diabetes and heart disease (1^✔ ✔Trusted Source
Mount Sinai Study Uncovers Genetic Factors Behind Individual Differences in Obesity Impact

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Large-Scale Genome Data Analysis

The team analyzed genetic data from 452,768 people and discovered variants in 205 regions of the genome linked to higher body fat but better metabolic health. Using these discoveries, they developed a genetic risk score that adds up the impact of these variants. Individuals with higher scores were more likely to develop obesity, but were less likely to suffer from complications such as high blood pressure, high cholesterol, diabetes, or heart disease. This is due, in part, to the way fat cells behave in different people.

Early Protective Effects in Children

Importantly, these protective genetic effects were already visible in children. Kids carrying the protective variants were more likely to develop obesity but did not show the expected warning signs of metabolic disease.

Understanding Obesity Subtypes

“Our study shows that obesity is not a single condition—it is made up of different subtypes, each with its own risks,” said Nathalie Chami, PhD, first author on this paper and Instructor of Environmental Medicine, and Artificial Intelligence and Human Health, at the Icahn School of Medicine. “By uncovering these genetic differences, we can start to understand why obesity leads to different health outcomes in different individuals. This could eventually change how we predict, prevent, and treat obesity and its complications.”

Eight Obesity Subtypes Identified

The research also identified eight distinct obesity subtypes, each linked to unique health risks. “These insights could eventually help doctors predict which patients are most vulnerable to complications and inform new treatments that mimic the protective genetic effects found in some people,” said Dr. Chami.

Lifestyle Factors Remain Critical

The research team cautions that the findings do not mean obesity is harmless. “Most people with obesity still face health challenges, and lifestyle factors such as diet and exercise remain critical for overall health” said Zhe Wang, PhD, co-first author on this paper, and Adjunct Assistant Professor of Artificial Intelligence and Human Health, at the Icahn School of Medicine; and Assistant Professor at the University of Alabama at Birmingham.

Expanding Research Across Populations

The study was conducted in individuals from the UK Biobank, comprising people of European ancestry, and future work will extend to more diverse populations. It leveraged this data to perform a comprehensive multi-trait genome-wide screen. The team wanted to find new genes that affect body fat without being linked to cardiometabolic comorbidities by analyzing three adiposity and eight cardiometabolic traits, including lipid, glycemic, and blood pressure traits.

Toward Personalized Care and Prevention

“By revealing new biological pathways that separate obesity from related diseases, the findings may pave the way for more personalized care, better-targeted therapies, and earlier prevention strategies—even from childhood,” said Ruth Loos, PhD, corresponding author, and Professor of Environmental Medicine at Icahn School of Medicine, and Professor at the University of Copenhagen in Denmark.

Reference:

1. Mount Sinai Study Uncovers Genetic Factors Behind Individual Differences in Obesity Impact - (https://bioengineer.org/mount-sinai-study-uncovers-genetic-factors-behind-individual-differences-in-obesity-impact/)

Source-Mount Sinai School of Medicine