Obesity is a disease of the nervous system. While some will view this statement as provocative, others will take it as obvious. Whatever our side is, the pharmacology tells us that targeting the nervous system works for promoting weight loss. It works, but at what cost? Is the nervous system a safe target for sustainable treatment of obesity? What have we learned-and unlearned-about the central control of energy balance in the last few years? Herein we provide a thought-provoking exploration of obesity as a disorder of neurotransmission. We discuss the state of knowledge on the brain pathways regulating energy homeostasis that are commonly targeted in anti-obesity therapy and explore how medications affecting neurotransmission such as atypical antipsychotics, antidepressants, and antihistamines relate to body weight. Our goal is to provide the endocrine community with a conceptual framework that will help expending our understanding of the pathophysiology of obesity, a disease of the nervous system.
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