Physiological and Lifestyle Traits of Metabolic Dysfunction in the Absence of Obesity

Individuals with metabolically unhealthy normal weight (MUNW) have an adverse cardiometabolic risk factor profile in the absence of excess body weight, and increased risk for diabetes and heart disease. We critically review some physiological traits and lifestyle characteristics of the MUNW phenotype.

The prevalence of MUNW varies considerably around the world and among ethnicities, partly because of different definitions; on average, this phenotype affects about ~ 30% of normal weight persons globally. Most studies have recruited MUNW subjects who, although within the normal weight range, are significantly "more obese" than their metabolically healthy lean peers (greater body mass index or total body fat); hence one cannot ascertain whether observed differences are true traits of the MUNW phenotype of simply secondary to greater relative adiposity within the normal range. Carefully matched studies have indicated that MUNW can exist in the absence of excess total body fat. These subjects have a preferential accumulation of fat in the upper body (abdominal subcutaneous and visceral adipose tissues) and the liver, but not skeletal muscle; perhaps surprisingly, this predominantly "android" fat distribution does not translate into increased waist circumference. The MUNW phenotype is associated with lower aerobic fitness and muscle mass and strength, but whether this is simply due to inadequate regular physical activity is not entirely clear. Likewise, no consistent associations have been found between any dietary factors and the development of MUNW phenotype, but diet-induced modest weight loss facilitates its resolution. Delineating the mechanisms leading to metabolic dysfunction in the absence of increased body weight and body fat will likely reveal important targets for improving metabolic health and eventually for reducing the burden of cardiometabolic disease, not only in individuals with normal body weight but also in people with obesity.