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  • Review Article
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Metabolically healthy obesity: from epidemiology and mechanisms to clinical implications

Nature Reviews Endocrinology volume 20, pages 633–646 (2024)Cite this article

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Abstract

The concept of metabolic health, particularly in obesity, has attracted a lot of attention in the scientific community, and is being increasingly used to determine the risk of cardiovascular diseases and diabetes mellitus-related complications. This Review assesses the current understanding of metabolically healthy obesity (MHO). First, we present the historical evolution of the concept. Second, we discuss the evidence for and against its existence, the usage of different definitions of MHO over the years and the efforts made to provide novel definitions of MHO. Third, we highlight epidemiological data with regard to cardiovascular risk in MHO, which is estimated to be moderately elevated using widely used definitions of MHO when compared with individuals with metabolically healthy normal weight, but potentially not elevated using a novel definition of MHO. Fourth, we discuss novel findings about the physiological mechanisms involved in MHO and how such knowledge helps to identify and characterize both people with MHO and those with metabolically unhealthy normal weight. Finally, we address how the concept of MHO can be used for risk stratification and treatment in clinical practice.

Key points

  • The concept of metabolically healthy obesity (MHO) is attracting a huge amount of attention in the scientific community.

  • Total cardiovascular risk in individuals with MHO, when compared with individuals with metabolically healthy normal weight, is moderately elevated using widely used definitions of MHO.

  • Cardiovascular mortality risk in individuals with MHO, when compared with individuals with metabolically healthy normal weight, might not be elevated when using a novel definition of MHO.

  • Novel genetic data strongly support the hypothesis that body adipose tissue distribution, including the ability to expand adipose tissue mass in the gluteofemoral adipose tissue compartment, is an important determinant of MHO.

  • As of today, the concept of MHO can be used for risk stratification and treatment in clinical practice.

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Fig. 1: Development of the metabolically healthy obesity concept over time.
Fig. 2: Process to establish a novel definition of metabolically healthy obesity.
Fig. 3: Cardiovascular risk in subgroups according to BMI and metabolic health status.
Fig. 4: Consequences of stability of metabolic health versus transition to a metabolically unhealthy phenotype for cardiovascular disease risk.
Fig. 5: Energy storage under positive energy balance and metabolic health.
Fig. 6: Potential strategies to identify and treat metabolically healthy and metabolically at-risk people with obesity.

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Acknowledgements

The authors acknowledge the support of funding from the German Federal Ministry of Education and Research (BMBF) to the German Centre of Diabetes Research (DZD) and the Stratification of Obesity Phenotypes to Optimize Future Obesity Therapy (SOPHIA) project. The authors thank M. Bauer (German Institute of Human Nutrition Potsdam-Rehbruecke) for assistance in literature handling and data extraction and E. Llanaj (German Institute of Human Nutrition Potsdam-Rehbruecke) for assistance in the preparation of the initial versions of the figures.

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Authors and Affiliations

  1. Department of Molecular Epidemiology, German Institute of Human Nutrition Potsdam-Rehbruecke, Nuthetal, Germany

    Matthias B. Schulze

  2. German Center for Diabetes Research, Neuherberg, Germany

    Matthias B. Schulze & Norbert Stefan

  3. Institute of Nutritional Science, University of Potsdam, Nuthetal, Germany

    Matthias B. Schulze

  4. Department of Internal Medicine IV, University Hospital Tübingen, Tübingen, Germany

    Norbert Stefan

  5. Institute of Diabetes Research and Metabolic Diseases (IDM) of the Helmholtz Centre Munich, Tübingen, Germany

    Norbert Stefan

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Schulze, M.B., Stefan, N. Metabolically healthy obesity: from epidemiology and mechanisms to clinical implications. Nat Rev Endocrinol 20, 633–646 (2024). https://doi.org/10.1038/s41574-024-01008-5

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