Metabolically healthy obesity: from epidemiology and mechanisms to clinical implications

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. This Review discusses the current understanding of the concept of metabolically healthy obesity (MHO), the challenges in defining MHO and how the MHO concept can be used to improve the prevention and treatment of cardiometabolic disease. 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.