Metabolically healthy obesity: facts and fantasies

Abstract

Although obesity is typically associated with metabolic dysfunction and cardiometabolic diseases, some people with obesity are protected from many of the adverse metabolic effects of excess body fat and are considered "metabolically healthy." However, there is no universally accepted definition of metabolically healthy obesity (MHO). Most studies define MHO as having either 0, 1, or 2 metabolic syndrome components, whereas many others define MHO using the homeostasis model assessment of insulin resistance (HOMA-IR). Therefore, numerous people reported as having MHO are not metabolically healthy, but simply have fewer metabolic abnormalities than those with metabolically unhealthy obesity (MUO). Nonetheless, a small subset of people with obesity have a normal HOMA-IR and no metabolic syndrome components. The mechanism(s) responsible for the divergent effects of obesity on metabolic health is not clear, but studies conducted in rodent models suggest that differences in adipose tissue biology in response to weight gain can cause or prevent systemic metabolic dysfunction. In this article, we review the definition, stability over time, and clinical outcomes of MHO, and discuss the potential factors that could explain differences in metabolic health in people with MHO and MUO - specifically, modifiable lifestyle factors and adipose tissue biology. Better understanding of the factors that distinguish people with MHO and MUO can produce new insights into mechanism(s) responsible for obesity-related metabolic dysfunction and disease.

Figure 1. Estimated prevalence of metabolically healthy and metabolically unhealthy obesity among people with obesity in North America and Europe based on the number of metabolic syndrome criteria and an assessment of insulin sensitivity (using the homeostasis model assessment of insulin resistance [HOMA-IR] score).

Data were derived from 33 studies involving a total of 123,548 people with obesity as described in the Supplemental Material (available online with this article; https://doi.org/10.1172/JCI129186DS1).

Figure 2. Putative characteristics of people with metabolically unhealthy obesity that are distinct from those of people with metabolically healthy obesity.

However, the evidence to support a difference in many of these characteristics between people with MUO and MHO is not definitive because of inadequate data or conflicting results from different studies.