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Obesity and metabolic disorders are becoming increasingly prevalent in many parts of the world, and have been accompanied by rising morbidity and associated health costs. This crisis has driven increased research efforts aimed at understanding the neurophysiological systems that regulate food intake and metabolism — and how these systems can become dysfunctional. Nature Reviews Neuroscience presents a series of articles examining various aspects of this regulation in health and disease, including the potential implications for the development of therapies.
The extent and contribution of maternal influence to the developing hypothalamus to later feeding behaviour remain controversial. In this Opinion, Zeltser proposes that crosstalk between developing circuits regulating different modalities of food intake shapes susceptibility to environmental challenges.
Coordination between peripheral signals that reflect feeding status and central regulatory mechanisms are crucial for regulating body weight. In this Review, Sandoval and colleagues discuss how and where peripherally derived signals are integrated within the CNS to modulate feeding behaviour.
The brain regulates adipose tissue metabolism through sympathetic efferent pathways; in turn, adipose tissues relay energy-status information to the brain. This Review gives an overview of interactions between the brain and adipose tissues, with a particular focus on leptin as a regulator of these communications.
Although leptin administration decreases food intake and body weight in lean mice, it has no effect in obese mice. In this Review, Pan and Myers discuss how leptin action becomes dysfunctional in obesity and suggest that elevated leptin levels promote processes that limit leptin action.
Eating patterns in modern societies often preclude the metabolic switch from utilization of glucose to ketones as a cellular energy source. In this Review, Mattson and colleagues discuss how intermittent metabolic switching impacts brain function and vulnerability to injury and disease.
The dopamine motive system, which integrates reinforcement and motivation, is influenced by obesogenic foods and addictive drugs. In this Review, Volkow and colleagues highlight how these stimuli sensitize the subject's motivation towards them while desensitizing the subject's motivation towards alternative reinforcers.