Here’s why obesity affects people differently

A global study found genetic variants that allow some people with obesity to stay metabolically healthier, identifying eight subtypes of obesity. The findings may enable personalised prevention and treatment strategies.

New Delhi: Ever wondered why some people with obesity remain relatively healthy while others develop serious conditions like diabetes and heart disease? Genetic differences may be the reason, according to a new study.

An international team of researchers led by the Icahn School of Medicine at Mount Sinai and the University of Copenhagen analysed genetic data from 452,768 people and discovered variants in 205 regions of the genome linked to higher body fat but better metabolic health.

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Using these findings, they developed a genetic risk score that accounts for the impact of these variants. Individuals with higher scores were more likely to develop obesity — but were less likely to suffer complications such as high blood pressure, high cholesterol, diabetes, or heart disease. This is partly due to the way fat cells behave in different people.

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 usual warning signs of metabolic disease, the study revealed. The research was published in Nature Medicine.

“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, Instructor of Environmental Medicine and Artificial Intelligence and Human Health, at the Icahn School.

“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,” Chami added.

The research 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,” Chami said.

The team cautioned, however, 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, Assistant Professor at the University of Alabama at Birmingham.

The study was conducted using individuals from the UK Biobank, comprising people of European ancestry. Future work will extend to more diverse populations. Researchers used this data to perform a comprehensive multi-trait genome-wide screen, analysing three adiposity traits and eight cardiometabolic traits, including lipid, glycemic, and blood pressure indicators.

“By revealing new biological pathways that separate obesity from related diseases, the findings may pave the way for more personalised care, better-targeted therapies, and earlier prevention strategies — even from childhood,” said Ruth Loos, Professor at the University of Copenhagen.