MECHANISMS IN ENDOCRINOLOGY: Are metabolically healthy obese individuals really healthy?

Obesity has become one of the major public health concerns of the past decades, because it is a key risk factor for type 2 diabetes, cardiovascular diseases, dyslipidemia, hypertension, and certain types of cancer, which may lead to increased mortality. Both treatment of obesity and prevention of obesity-related diseases are frequently not successful. Moreover, a subgroup of individuals with obesity does not seem to be at an increased risk for metabolic complications of obesity. In this literature, this obesity subphenotype is therefore referred to as metabolically healthy obesity (MHO). Importantly, individuals with MHO do not significantly improve their cardio-metabolic risk upon weight loss interventions and may therefore not benefit to the same extent as obese patients with metabolic comorbidities from early lifestyle, bariatric surgery, or pharmacological interventions. However, it can be debated whether MHO individuals are really healthy, especially since there is no general agreement on accepted criteria to define MHO. In addition, overall health of MHO individuals may be significantly impaired by several psycho-social factors, psychosomatic comorbidities, low fitness level, osteoarthritis, chronic pain, diseases of the respiratory system, the skin, and others. There are still open questions about predictors, biological determinants, and the mechanisms underlying MHO and whether MHO represents a transient phenotype changing with aging and behavioral and environmental factors. In this review, the prevalence, potential biological mechanisms, and the clinical relevance of MHO are discussed.