The receptive function of hypothalamic and brainstem centres to hormonal and nutrient signals affecting energy balance

Abstract

The hypothalamic arcuate nucleus (ARC) and the area postrema (AP) represent targets for hormonal and metabolic signals involved in energy homoeostasis, e.g. glucose, amylin, insulin, leptin, peptide YY (PYY), glucagon-like peptide 1 (GLP-1) and ghrelin. Orexigenic neuropeptide Y expressing ARC neurons are activated by food deprivation and inhibited by feeding in a nutrient-dependent manner. PYY and leptin also reverse or prevent fasting-induced activation of the ARC. Interestingly, hypothalamic responses to fasting are blunted in different models of obesity (e.g. diet-induced obesity (DIO) or late-onset obesity). The AP also responds to feeding-related signals. The pancreatic hormone amylin acts via the AP to control energy intake. Amylin-sensitive AP neurons are also glucose-responsive. Furthermore, diet-derived protein attenuates amylin responsiveness suggesting a modulation of AP sensitivity by macronutrient supply. This review gives an overview of the receptive function of the ARC and the AP to hormonal and nutritional stimuli involved in the control of energy balance and the possible implications in the context of obesity. Collectively, there is consistency between the neurophysiological actions of these stimuli and their effects on energy homoeostasis under experimental conditions. However, surprisingly little progress has been made in the development of effective pharmacological approaches against obesity. A promising way to improve effectiveness involves combination treatments (e.g. amylin/leptin agonists). Hormonal alterations (e.g. GLP-1 and PYY) are also considered to mediate body weight loss observed in obese patients receiving bariatric surgery. The effects of hormonal and nutritional signals and their interactions might hold the potential to develop poly-mechanistic therapeutic strategies against obesity. Arcuate nucleus: Area postrema: Food intake: ObesityDriven by the search for therapeutic treatment strategies against obesity and associated metabolic disorders, considerable knowledge has accumulated about the control mechanisms involved in the maintenance of energy balance. The redundancy of control mechanisms, the capacity of these systems to compensate for pharmacological effects and the existence of obesity-related hormonal insensitivities make it difficult to achieve sufficient therapeutic efficiency for the reduction of body weight over longer periods of time. Evidently, at least under nonlaboratory conditions, so-called non-homoeostatic factors (hedonic properties and availability of food, food preferences, social factors, eating habits, etc.) and central reward mechanisms override homoeostatic hormonal and metabolic signals that are considered to reflect and to control the body's energy status.

Physiology of leptin: energy homeostasis, neuroendocrine function and metabolism

“…Leptin appears to act synergistically with GLP-1 and CCK in the NTS to promote satiety [29]. Peptide YY (PYY) is released from L cells of the ileum and colon in response to feeding, crosses blood-brain barrier and acts on Y2 receptor on NPY neurons in the ARC to inhibit the release of NPY, thereby reducing food intake in mice and humans [30, 31]. Peripheral administration of PYY in mice also activates neurons in the NTS, which may partly influence food intake.…”

Hypothalamic expression of anorexigenic and orexigenic hormone receptors in obese femalesNeotomodon alstoni:Effect of fasting

“…Both leptin and ghrelin are endocrine signals out of balance in conditions of obesity. 14,15 Pituitary adenylate cyclase-activating polypeptide (PACAP) and vasoactive intestinal peptide (VIP) are also involved in food intake in various species. 16 Both ligands act through common receptors such as VPACR-1 and VPACR-2, also known as PACAP/ VIP mutual receptors; VIP and PACAP are actively expressed in the hypothalamus and participate in the control of appetite and energy homeostasis.…”

Strength Training and Physical Activity in Boys: a Randomized Trial

“…6 The arcuate nucleus of the hypothalamus is recognized as the brain' s command center for controlling energy balance. 7 Along with other hypothalamic and brainstem nuclei, the neurons of the arcuate nucleus coordinate energy intake and expenditure. Although most reviews discussing the regulation of energy balance are focused on food intake, little is known about the regulation of spontaneous PA in childhood.…”