![]() ![]() Increasing NPY tone pharmacologically results in hyperphagia and reduced thermogenesis of brown adipose tissue (BAT), associated with diminished activity of the thyroid axis ( Clark et al. The expression and release of ARC NPY respond to changes in energy status, being reduced under feeding conditions and increased under fasting conditions ( Beck et al. NPY is widely expressed throughout the CNS, but it is most densely localized in the ARC in the hypothalamus ( Gehlert et al. This neuronal circuit is crucial for sensing and integrating a number of peripheral signals allowing for a precise control of food intake and energy expenditure (see section ‘ARC neuronal circuits: POMC, AgRP, and RIPCre neurons’). These two populations of neurons (hereafter referred to as AgRP and POMC respectively), together with downstream target neurons expressing the melanocortin receptor 4 (MC4R) and MC3R, constitute the central melanocortin system. In the ARC, there are at least two major populations of neurons controlling appetite and energy expenditure: i) a subset of neurons that coexpress orexigenic neuropeptide Y (NPY) and agouti-related peptide (AGRP) and ii) a population of neurons that coexpress the anorexigenic neuropeptides cocaine- and amphetamine-regulated transcript (CART (CARTPT)) and α-melanocyte-stimulating hormone (α-MSH, a product of proopiomelanocortin (POMC) processing). This area has a semi-permeable blood–brain barrier (BBB Broadwell & Brightman 1976), and thus it is strategically positioned to sense hormonal and nutrient fluctuations in the bloodstream. It is located below the VMN, on both sides of the third ventricle, and immediately adjacent to the median eminence (ME). The ARC is a very important area of the CNS involved in the control of energy homeostasis. The present review attempts to summarize current understanding of the anatomy, neurochemistry, functions, and interactions of relevant neural circuits involved in the homeostatic regulation of energy balance. Despite the precision of these systems in matching energy demand with energy expenditure, contemporary, and lifestyle factors are the main causes of the prevailing obesity epidemics. ![]() The immense complexity of these systems illustrates the biological importance of adequate nutrient and energy balance, a process that has been evolutionarily conserved and refined to guarantee appropriate adiposity levels. These sophisticated biological programs are influenced by multiple factors, including environmental, genetic, and epigenetic mechanisms. The regulation of appetite and body weight is an intricate process controlled by redundant and distributed neural systems that integrate a myriad of cognitive, hedonic, emotional, and homeostatic cues to precisely regulate systemic energy balance through behavioral, autonomic, and endocrine outputs. ![]()
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