Abstract
Metabolically healthy obesity refers to an obesity phenotype with no or little evidence of metabolic dysfunction. Lower liver fat content and visceral adipose tissue, greater insulin sensitivity and secretion, greater cardiorespiratory fitness, and a predominantly lower body (i.e., leg) fat deposition are key physiological traits of a metabolically healthy phenotype. About 35% of all subjects with obesity are metabolically healthy. These individuals have approximately half the risk of developing type 2 diabetes and cardiovascular disease compared with metabolically unhealthy subjects with obesity, but they still have a significantly greater risk (by 50-300%) compared with metabolically healthy lean subjects. Therefore, absence of metabolic risk factors in people with obesity should not be a contraindication for weight-loss treatment. Metabolically healthy obesity needs to be treated, and this need is reinforced by the fact that this phenotype is not stable over time, as ∼50% of these subjects will cease being metabolically healthy within ∼10 y. Intervening early is therefore important. Weight loss dose-dependently decreases visceral adipose tissue and liver fat content, and it improves multiorgan insulin sensitivity and β-cell function (i.e., it beneficially affects many of the physiological traits of a metabolically healthy phenotype); however, weight loss is very difficult to maintain. This typically results in disappointment among patients and hinders adherence, which is likely critical for the limited success of most weight-loss treatments in the long term. On the other hand, using ≥1 metabolic health targets in a non-weight-loss-centered treatment paradigm that includes prudent dietary changes and increased physical activity can serve as an appropriate first goal that can help motivate patients toward the long-term goals of obesity treatment.
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