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.