Introduction The hypothalamus is a critical integrator of peripheral and central signals that mediate energy homeostasis. Over the last two decades, substantial progress has been made in elucidating the details of how neural, hormonal and nutrient signals from the gut and adipose tissue act on specific hypothalamic pathways to control energy balance and various physiologic processes. These hypothalamic circuits affect not only appetite, but through their diverse projections to the autonomic nervous system, brainstem and higher centers also influence motivational and motor function, and the endocrine system via the pituitary gland. Although the details of the interacting factors and effector mechanisms remain an area of active research, it is clear that neuropeptides at the level of the hypothalamus modulate key aspects of feeding behavior, energy expenditure and neuroendocrine function (Grill & Kaplan, 2002). In this chapter, we provide an overview of the hypothalamic circuitry within a framework for understanding its role as a sensor, integrator and effector of energy homeostasis and diverse physiologic processes. Classical role of the hypothalamus in feeding regulation A crucial involvement of the base of the diencephalon in energy homeostasis was first suggested by clinical observations in patients with pituitary tumors associated with excessive fat deposition and hypogonadism (Bramwell, 1888; Frolich, 1901). Several animal studies confirmed the importance of this region in body weight regulation, but it was not until the experiments of Hetherington and Ranson that the role of the hypothalamus rather than that of the pituitary gland was firmly established.
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