Lean, but not healthy: the 'metabolically obese, normal-weight' phenotype

Obesity is commonly associated with metabolic dysfunction but there are obese persons who are metabolically healthy. On the opposite side of the coin, there are lean persons who carry multiple cardiometabolic risk factors, typically referred to as metabolically obese, normal-weight (MONW). This has called into question our understanding of obesity and metabolic dysfunction, as an appearance of normal weight may mask significant comorbidities and delay health interventions.

High heterogeneity in MONW prevalence rates has been observed, with estimates ranging from as low as 5% to as high as 45%. Reasons for this include sample size effects, differences in MONW definition, social and demographic factors, as well as assumptions made in establishing normal weight. MONW study participants are often characterized by excess visceral adipose tissue and ectopic fat deposition, adipose tissue inflammation, altered inflammatory and adipokine profiles, reduced skeletal muscle mass and low cardiorespiratory fitness. However, more often than not, groups of MONW study participants have been somewhat 'fatter' than the control groups of metabolically healthy lean study participants, which in itself could be responsible for some of the observed differences. Very limited data are available regarding interventions to improve metabolic function in MONW study participants.

There is a need for more research to better understand the characteristics of the MONW phenotype, the cause of metabolic dysfunction in the absence of obesity, and evaluate potential therapies so as to facilitate the establishment of clinical guidelines.