Distribution and Characteristics of Brain Dopamine
Nira Ben-Jonathan in Dopamine, 2020
The arcuate nucleus is located near the third ventricle and above the median eminence. It is composed of a diverse population of neurons as well as nonneuronal cells such as astrocytes and tanycytes, which are specialized ependymal cells. The arcuate nucleus contains large amounts of DA and is the origin of the TIDA and THDA neurons that innervate the median eminence and the posterior pituitary, respectively, as discussed in Sections 3.4.3 and 3.4.4. The parvocellular neurons within the arcuate nucleus produce several releasing/inhibiting hormones that include GnRH, GH releasing hormone (GHRH), β-endorphin, melanocyte stimulating hormone (MSH) and somatostatin. In addition, the arcuate nucleus produces a variety of neuromodulators such as kisspeptin, NPY, substance P, Agouti-related peptide (AgRP) and CART (cocaine and amphetamine regulatory transcript). The arcuate nucleus has the highest concentrations of leptin receptors in the brain and as discussed in Chapter 4, it is the best characterized hypothalamic nucleus involved in energy homeostasis.
Energy balance and its regulation
Geoffrey P. Webb in Nutrition, 2019
The arcuate nucleus of the hypothalamus now seems to play a key role in receiving and responding to both short- and long-term signals that reflect the body’s feeding and nutritional status and thus control body weight. Circulating factors can interact directly with neurones of the arcuate nucleus because it is incompletely separated from the general circulation by the blood–brain barrier. There are sub-populations of neurones within the arcuate nucleus involved in food intake regulation: some that are appetite inhibiting (anorexigenic) and some that are appetite stimulating (orexigenic). The orexigenic neurones release peptides like neuropeptide Y (NPY) and agouti-related peptide (AgRP) to receptors within the central nervous system to produce appetite stimulation, whilst anorexigenic neurones release proopiomelanocortin (POMC) and cocaine and amphetamine transcript (CART) to produce an anorectic response.
The metabolic basis of obesity
Anna Bellisari in The Anthropology Of Obesity in the United States, 2016
The arcuate nucleus, one of the hypothalamic nerve centers, contains two sets of neurons with opposing functions for controlling food intake, one as stimulator and the other as inhibitor (Ulijaszek and Lofink 2006; Woods et al. 1998). Generally, a signal that activates one set simultaneously inhibits the opposite set. For example, the neurons that stimulate food intake also turn down the rate of energy expenditure and heat dissipation to conserve energy. To resist eating, a dieter must consciously override this potent appetite-promoting, energy-conserving system. On the other hand, finishing a full meal sends satiety signals to turn off the appetite-stimulating neurons and suppresses further energy intake via efferent signals to the brainstem. The neurons that inhibit food intake simultaneously turn up the metabolic rate and energy dissipation. This system also monitors energy required for reproduction and in severely malnourished women shuts down ovulation.
Psychopharmacological advances in eating disorders
Published in Expert Review of Clinical Pharmacology, 2018
Hubertus Himmerich, Janet Treasure
The hypothalamus plays a central role in the homeostatic system regulating of food intake and body weight. It integrates signals about the nutritional state and food supply from the periphery and modulates food intake and energy consumption [73,74]. An important orexigenic signal leading to hunger and food intake is ghrelin which is produced in the stomach [75]. Anorexigenic signals from the body periphery include glucose, the enterocyte hormone GLP-1 [76], the pancreatic hormone insulin, and the fatty tissue hormone leptin [74]. In the hypothalamus, the arcuate nucleus, the paraventricular nucleus, and the lateral hypothalamus are of particular relevance for weight regulation [74,77]. The arcuate nucleus integrates the incoming humoral signals of GLP-1, insulin, leptin, ghrelin, and other hormones and energy carriers such as glucose and converts them into neuronal signals. Orexigenic hypothalamic signaling molecules are NPY and AgRP which lead to an increase in appetite, while α-MSH as well as CART are anorexic signals which lead to a feeling of satiety [74]. α-MSH is produced by the so-called pro-opiomelanocortin (POMC) neurons [78]. In acute episodes of AN, for example, ghrelin has been found to be overexpressed, and leptin reduced as would be expected in starvation [94]. However, plasma levels of NPY (part of the orexigenic system) are anomalously low [94]. Abnormalities within the hormonal regulation of the homeostatic system have also been reported for BN [108] and BED [109].
Novel approaches to anti-obesity drug discovery with gut hormones over the past 10 years
Published in Expert Opinion on Drug Discovery, 2019
Frances Rose, Stephen Bloom, Tricia Tan
Peptide YY (PYY) is a hormone belonging to the pancreatic polypeptide (PP) family, and is secreted by the neuroendocrine L-cells of the small intestine in response to eating [28]. Its effect is mediated through the neuropeptide Y (NPY) receptors, of which there are several subtypes. The hypothalamic arcuate nucleus, which is a key area in central appetite regulation, expresses the Y2 receptor (Y2R). PYY3–36 is derived from full length PYY1–36 by dipeptidyl peptidase-IV (DPP-IV), and is more selective for Y2R. Plasma PYY3–36 levels rise within 15 minutes of ingesting food, with peak levels proportional to the number of calories ingested [29]. Administration of PYY by infusion in humans leads to reduced food intake, an effect which is preserved in obesity. Obese subjects have also been shown to have lower endogenous levels of PYY, therefore making it a potential therapeutic target for appetite suppression [30].
An update on pharmacotherapeutic strategies for obesity
Published in Expert Opinion on Pharmacotherapy, 2021
Beverly G. Tchang, Mohamad Sirri Tarazi, Mohini Aras, Alpana P. Shukla
Obesity afflicts nearly 40% of adult Americans [1], and almost one of every two Americans is projected to have obesity by 2030 [2]. While obesity has traditionally been defined and classified by the body mass index (BMI), its pathophysiology has driven some in the scientific community to consider redefining it as adiposity-based chronic disease [3], characterized by impaired homeostatic mechanisms in energy regulation and inflammation [4,5]. The physiology of appetite and energy regulation is controlled by the arcuate nucleus of the hypothalamus, which contains orexigenic and anorexigenic neurons that respond to peripheral signals to increase (e.g. ghrelin, cortisol) or decrease (e.g. leptin, catecholamines) appetite. In the pathophysiology of obesity, the arcuate nucleus’s homeostatic control on appetite can be overridden by other central neural signals, such as the dopamine reward system, and can be disrupted by inflammation [6]. In rodent models of obesity, a high-fat diet was found to induce reactive gliosis, a marker of inflammation, in hypothalamic neurons, which was associated with a reduction in the number of pro-opiomelanocortin (POMC) cells in the arcuate nucleus after chronic exposure to the high-fat diet [6]. A state of leptin resistance has also been characterized in obesity and may contribute to energy dysregulation [7]. The accumulation of adipose tissue in the setting of weight gain and obesity, particularly in visceral depots, has been associated with a proinflammatory and prothrombotic milieu that is posited to be a contributor to multiple comorbid conditions, including type 2 diabetes (T2D), hypertension, and cardiovascular disease (CVD).
Related Knowledge Centers
- Median Eminence
- Neuropeptide
- Third Ventricle
- Astrocyte
- Neurotransmitter
- Pituitary Gland
- Homeostasis
- Neuron
- Hypothalamus
- Hormone