Neural Orchestration of Food Intake and Energy Expenditure


Eating is one of the most hard‐wired and ubiquitous behaviours. Yet, we have only begun to map the neural circuits underlying its control. By sensing peripheral metabolic states via hormonal signals such as leptin, insulin, ghrelin and cholecystokinin, circuits composed of specific cell types either drive or suppress food intake. Homeostatic inhibitory neurons of the hypothalamic arcuate nucleus co‐expressing agouti gene‐related protein and neuropeptide Y coordinate hunger through divergent projections, while additional circuitry seems dedicated to hedonic feeding and the motivation to eat. In contrast, the vagus nerve delivers visceral information to broadly projecting neurons of the nucleus tractus solitarius to acutely suppress appetite. One of their downstream targets includes excitatory calcitonin gene‐related peptide‐expressing neurons of the parabrachial nucleus that project to the central amygdala. Distinct circuitry seems to regulate energy expenditure and body weight independent of feeding. Hence, the nervous system differentially stimulates and suppresses eating via a number of separate, neuroanatomically distributed and molecularly distinct circuits.

Key Concepts

  • Peripheral metabolic signals influence neurons either by circulating through the blood and passing from vasculature into the central nervous system or by acting on interoceptive sensory neurons of the vagus nerve.
  • Each peripheral metabolic signal has the potential to have widespread and coordinated effects on different neural populations.
  • Separable neural circuitry is dedicated to appetite stimulation versus appetite suppression.
  • Considering either the neural circuitry of appetite stimulation or suppression, there are a number of circuit‐level mechanisms that likely interact and act in parallel.
  • Some neural circuits appear to affect energy expenditure independent of feeding.

Keywords: eating; feeding; appetite; circuit; AgRP ; POMC ; vagus; NTS; PBN; CeA

Figure 1. Sagittal sections of the rodent brain illustrating the two general mechanisms by which peripheral metabolic signals can have widespread and coordinated effects on neural populations. (a) A peripheral signal can pass from the vasculature into different brain regions expressing its receptor. As an example, the outlined regions represent those with expression of the leptin receptor (Elmquist et al., ; Grill and Hayes, ). (b) Peripheral signals can also activate the vagus nerve, which then relays visceral information to broadly projecting neurons of the nucleus tractus solitarius (NTS) (Grill and Hayes ; Alhadeff et al., , ). AP, area postrema; ARC, arcuate nucleus; CB, cerebellum; DMH, dorsomedial hypothalamus; DMX, dorsal motor nucleus of the vagus; DRN, dorsl raphe nucleus; LGN, lateral geniculate nucleus; LHA, lateral hypothalamus; NAc, nucleus accumbens; PBN, parabrachial nucleus; PIR, piriform cortex; PVH, paraventricular nucleus of the hypothalamus; VMH, ventromedial hypothalamus; VTA, ventral tegmental area.
Figure 2. Parallel projections of AgRP neurons with distinct circuits to different downstream neural populations. Those circuits that are sufficient to stimulate feeding are coloured in green, whereas those that are not are in black. The arrowheads represent excitation and the flat‐heads inhibition. For simplicity, the one‐to‐one projection pattern of distinct aBNST, anterior bed nucleus of the stria terminalis; AgRP, agouti gene‐related protein; ARC, arcuate nucleus; CeA, central amygdala; LHA, lateral hypothalamus; NPY, neuropeptide Y PAG, periaqueductal grey; PBN, parabrachial nucleus; POMC, pro‐opiomelanocortin; PVH, paraventricular nucleus of the hypothalamus; and PVT, paraventricular thalamic nucleus.
Figure 3. An example of the neural circuitry that acutely suppresses appetite. A peripheral satiety signal, for example, cholecystokinin (CCK), activates the vagus nerve, which then relays visceral information to neural populations of the nucleus tractus solitarius (NTS), including those expressing pro‐opiomelanocortin (POMC), glucagon‐like peptide‐1 (GLP‐1) and norepinephrine (NE). NTS neurons provide excitatory input to neurons of the parabrachial nucleus (PBN), such as those expressing calcitonin gene‐related peptide (CGRP). PBN CGRP neurons in turn provide excitatory input to central amygdala (CeA) neurons expressing protein kinase C‐δ (PKC‐δ). The appetite‐relevant downstream targets of CeA PKC‐δ neurons have yet to be identified. The molecular nature of the NTS input to PBN CGRP neurons is also unknown. Note that POMC, GLP‐1 and NE are not necessarily expressed by the same population of NTS neurons, as POMC expression does not colocalise with that of GLP‐1 or NE (Cone, ). For simplicity, the broad projections of NTS neurons have been excluded. The arrowheads represent excitation and the flat‐head inhibition.


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Further Reading

Fenno L , Yizhar O and Deisseroth K (2011) The development and application of optogenetics. Annual Review of Neuroscience 34: 389–412.

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Soleiman, Matthew T(Apr 2015) Neural Orchestration of Food Intake and Energy Expenditure. In: eLS. John Wiley & Sons Ltd, Chichester. [doi: 10.1002/9780470015902.a0003378.pub2]