Hypothalamus

The hypothalamus is at the base of the brain, above the pituitary gland. The hypothalamus governs higher autonomic control, including mechanisms that maintain constancy of the internal environment. Included are controls of food intake and energy expenditure, making the hypothalamus important for regulating body weight and adiposity.

The hypothalamus is part of the diencephalon. It lies beneath the thalamus and borders the third cerebral ventricle. The hypothalamus is divided into nuclear areas distinguishable by cell appearance and neuropeptide and neurotransmitter contents. Hypothalamic nuclei and other brain areas communicate via complex neural circuits. There are also neural connections between the hypothalamus and the posterior lobe of the pituitary gland, and vascular connections with the anterior lobe of the pituitary gland. Thus, distinct populations of hypothalamic neurons are positioned to influence neural activity in other brain regions, as well as the release of pituitary hormones, and govern body temperature, “appetitive” processes such as food and water intake and sexual behavior, defensive reactions, and various endocrine and activity rhythms.

The hypothalamus receives nutrient, neural, and hormonal inputs indexing whole-body energy status, integrates these signals, and coordinates central nervous system and peripheral mechanisms that defend energy balance. In a simplified model, for example, the arcuate nucleus is a main receiver [Page 382]of energy signals. The arcuate nucleus contains two neuron types with receptors for both leptin and insulin, hormones that indicate, respectively, fat mass and levels of blood glucose. One neural population makes proopiomelanocortin (POMC), precursor of alpha-melanocyte-stimulating hormone, which stimulates melanocortin-3 and -4 receptors, resulting in decreased food intake and increased energy expenditure. Food deprivation or underweight decreases, and overconsumption or overweight increases POMC. Other arcuate neurons make neuropeptide Y (NPY) and the melanocortin-3 and -4 receptor inhibitor agouti-related protein (AgRP), which increase food intake and decrease energy expenditure. Food deprivation and underweight increase NPY and AgRP, and overconsumption and overweight decrease them.

The NPY/AgRP and POMC neurons project to the paraventricular nucleus (PVN), lateral hypothalamic area (LH), and other hypothalamic nuclei with receptors for these neuropeptides. PVN is important in anorexigenic/catabolic signaling, whereas the LH is involved in orexigenic/anabolic signaling. The PVN contains multiple neuronal subtypes that make oxytocin, corticotrophin-releasing hormone, or other neuropeptides that lead to reduced food intake or increased energy expenditure. The LH contains neurons that produce either orexins or melanin concentrating hormone, which increase feeding. PVN and LH projections to the pituitary gland and other brain sites mediate these effects on energy balance.