Is obesity a brain disease?

That the brain is involved in the pathogenesis and perpetuation of obesity is broadly self-intuitive, but traditional evaluation of this relationship has focused on psychological and environment-dependent issues, often referred to as the "it's all in the head" axiom. Here we review evidence that excessive nutrition or caloric flux, regardless of its primary trigger, elicits a biological trap which imprints aberrant energy control circuits that tend to worsen with the accumulation of body fat. Structural and functional changes in the brain can be recognized, such as hypothalamic inflammation and gliosis, reduction in brain volume, reduced regional blood flow or diminished hippocampal size. Such induced changes collectively translate into a vicious cycle of deranged metabolic control and cognitive deficits, some of which can be traced back even to childhood or adolescence. Much like other components of the obese state, brain disease is inseparable from obesity itself and requires better recognition to allow future therapeutic targeting.