TABLE OF CONTENTS 1. Abstract 2. Hypothalamic arcuate nucleus control of energy metabolism 3. Leptin 4. Ghrelin 5. Insulin 6. Thyroid hormones 7. Glucocorticoids 8. Perspectives 9. Acknowledgements 10. References ABSTRACT Over the past century, the hypothalamus has emerged as one of the critical sites involved in energy homeostasis. Degeneration studies in rats performed some six decades ago, first led to identifying hypothalamic subregions controlling food intake and body weight. The idea that

more »

... the central nervous system (CNS), and the hypothalamus in particular, are key in metabolism regulation was reinforced by the discovery of leptin in 1994. Since the identification of leptin, enormous progress has been made in the understanding of the regulation of hypothalamic and extrahypothalamic brain regions that control food intake and energy expenditure by peripheral signals such as hormones. An important challenge is to decipher these complicated interactions between peripheral signals and neuronal circuits to better understand the etiology of metabolic disorders and to identify opportunities to intervene with pharmacological treatment. In this review, we focus on the hormonal regulation of the neuronal circuits of the arcuate nucleus of the hypothalamus: the melanocortin system. HYPOTHALAMIC ARCUATE NUCLEUS CONTROL OF ENERGY METABOLISM The hypothalamus consists of several nuclei involved in the regulation of food intake. One of the most studied hypothalamic nuclei is the arcuate nucleus (ARC). The ARC, located at the medial base of the hypothalamus around the third ventricle, contains at least two distinct groups of neurons controlling energy balance: the orexigenic neuropeptides; agouti-gene-related protein (AgRP) and neuropeptide Y (NPY) containing neurons, and the anorexigenic neuropeptides; pro-opiomelanocortin (POMC) and cocaine and amphetamine-regulated transcript (CART) expressing neurons. Both the AGRP/NPY and the POMC/CART neurons have been identified as main regulators of appetite, satiety, and the regulation of energy expenditure. Because of their proximal location to the median eminence (ME) where the blood brain barrier (BBB) is not present (1), these neurons are responsive to many peripheral signals including leptin, insulin, glucocorticoids, ghrelin, thyroid hormones and many other hormones. These