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Obesity

Illuminating the ‘healthy obese’ phenotype

Nature Metabolism volume 5, pages 193–194 (2023)Cite this article

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Some individuals with obesity have a healthy metabolic profile and are not at increased risk for diabetes or cardiovascular disease. The mechanisms behind this phenomenon are poorly understood, but recent work now characterizes the biological underpinnings of the metabolically healthy obese phenotype.

The global prevalence of obesity has risen dramatically, and today more than 670 million adults are obese1. Obesity is often caused by an unhealthy diet and lifestyle: factors that promote a detrimental metabolic profile characterized by hyperglycaemia, insulin resistance, hypertension or hypercholesteraemia. Obesity is defined as having a body mass index (BMI) of 30 kg m−2 or more. However, obesity is a crude measure of adiposity, and two individuals with the same BMI can vary in the amount and distribution of adipose tissue, as well as having very different reasons for their obesity. Obesity is a highly polygenic trait, and, beside lifestyle factors, thousands of genetic variants have been shown to influence BMI and other adiposity-related traits2. Among these genetic variants, most of the alleles that increase the risk of obesity are also associated with poor metabolic health. However, some of the BMI-increasing alleles have been associated with a more favourable metabolic profile. An explanation for this discordance, which could shed light on the causal mechanisms behind obesity-associated diseases and offer new leads for pharmaceutical development and risk assessment, is still lacking.

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Fig. 1: Two individuals with the same BMI can have very different risks for T2D.

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Acknowledgements

A.J. is supported by the Swedish Research Council (2019-01497), the Swedish Heart-Lung foundation (20200687) and the Swedish Cancer Society (22 2222 Pj). M.R.-A. is supported by the Marcus Borgström and Åke Wiberg Foundations.

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  1. Department of Immunology, Genetics and Pathology, Science for Life Laboratory, Uppsala University, Uppsala, Sweden

    Mathias Rask-Andersen & Åsa Johansson

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  1. Mathias Rask-Andersen
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  2. Åsa Johansson
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Correspondence to Åsa Johansson.

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Rask-Andersen, M., Johansson, Å. Illuminating the ‘healthy obese’ phenotype. Nat Metab 5, 193–194 (2023). https://doi.org/10.1038/s42255-022-00733-3

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