Overweight is risking fate

Obesity is the result of ancient evolutionary survival mechanisms in a modern environment of affluence. When pressures from this environment generate a long-term or chronic hypothalamic arousal, neuroendocrine–endocrine and autonomic nervous systems are activated, leading to disease-generating ‘risk factors’ including the metabolic syndrome, with visceral fat accumulation as a conveniently observable marker. The susceptibility to develop these co-morbidities is probably dependent on a functional defect of the inhibitory feedback control of the hypothalamus–pituitary–adrenal axis by central glucocorticoid receptors, often based on a prevalent polymorphism of the gene locus for this receptor. This means that moderate (‘peripheral’) obesity is a fairly innocent condition while, when hypothalamic arousal is added, as indicated by the internalization of excess body fat (‘central’ obesity), a highly malignant condition develops in genetically susceptible individuals. Obesity research would benefit from a distinction between these two types of condition.