Neural systems controlling food intake and energy balance in the modern world

Obesity continues to increase around the globe, and creates a major health problem because of its comorbidities such as diabetes and cardiovascular disease. Considering that the major cause of most human obesities is the modern lifestyle in a rapidly changing environment, this suggests that the battle is between brain areas controlling internal metabolic homeostasis and those dealing with cognitive and emotional processing of external information. Thus, this review is intended to bridge this apparent neural dichotomy and highlight possible ways of interactions between these homeostatic and nonhomeostatic systems.

Rapid progress has been made in identifying the molecular mechanisms underlying the neural circuits regulating food intake and energy balance. Specific populations of peptidergic neurons in the medial hypothalamus can be considered metabolic integrators sensing both short and long-term availability of fuels. These cell groups in turn connect with various other brain regions to orchestrate adaptive responses through changes in food intake, as well as endocrine and autonomic responses. Alternatively, the impact of the environmental changes on ingestive behavior have been documented, and many of the underlying cortico-limbic pathways are starting to be identified. It has been proposed that a switch from instinctual control of energy balance to a more cognitive control will be necessary to stop the obesity epidemic.

The realization that there is nothing wrong with the homeostatic regulatory system in common obesity suggests that a systematic investigation of pathways that link the 'cognitive' with the 'metabolic' brain might be a more promising area of research. Such an investigation would reveal new molecular and cellular mechanisms providing new drug targets, leading to behavioral therapies that are directed more towards the causes of common obesity.