Central Nervous System Regulation of Food Intake

The central nervous system (CNS) governs food intake through a distributed network of hypothalamic and brainstem nuclei that integrate hormonal, nutritional and neural signals. Within the arcuate nucleus of the hypothalamus, orexigenic agouti-related peptide (AgRP) neurons and anorexigenic pro-opiomelanocortin (POMC) neurons respond oppositely to changes in energy status, driving hunger or satiety, respectively. These neurons relay information to downstream centres, including the paraventricular nucleus and lateral hypothalamus, and engage brainstem structures such as the nucleus of the solitary tract to fine-tune meal size and frequency. Peripheral hormones—leptin from adipose tissue, insulin from the pancreas and ghrelin from the stomach—modulate the firing rates of these populations, while vagal afferents convey immediate visceral feedback. Beyond hard-wired circuits, recent data reveal that specialised glial-like cells called tanycytes contribute to hypothalamic neurogenesis and plasticity, suggesting an adaptive capacity in energy-balance pathways. Overall, CNS regulation of feeding represents a dynamic interplay between rapid neural reflexes and slower hormonal cues, ensuring metabolic homeostasis and appropriate behavioural responses to nutrient availability.

Research from Nature Portfolio

Recent studies have mapped a brainstem-forebrain circuit critical for anorexia: cholecystokinin-expressing and noradrenergic neurons in the nucleus of the solitary tract directly excite calcitonin gene-related peptide-expressing neurons in the lateral parabrachial nucleus, and activation of this pathway by optogenetic or chemogenetic methods sharply reduces food intake and body weight in mice. In parallel, investigations into the adult hypothalamic niche have identified dorsal α-tanycytes as a stem-like population that gives rise to new neurons and glia. These α-tanycytes require local fibroblast growth factor signalling for proliferation and contribute to the replenishment of feeding-related circuits, hinting at a regenerative mechanism that may adjust energy-balance control over time.

Central Nervous System Regulation of Food Intake publication trend

The graph below shows the total number of articles in central nervous system regulation of food intake across all publications each year (not limited to Nature Index journals).

Technical terms

G protein-coupled receptor (GPCR): A large family of cell-surface receptors that transduce extracellular signals via G-protein activation.

Nucleus of the solitary tract (NTS): A medullary brainstem nucleus that receives visceral afferent input and relays satiety signals.

Parabrachial nucleus (PBN): A pontine structure that processes visceral and gustatory information, influencing feeding and aversive behaviours.

α-Tanycytes: Specialized ependymal cells lining the third ventricle that act as neural progenitors in the adult hypothalamus.

Agouti-related peptide (AgRP) neurons: Hypothalamic neurons that promote feeding and decrease energy expenditure.

Pro-opiomelanocortin (POMC) neurons: Hypothalamic neurons that suppress appetite and increase energy consumption.

Melanocortin 4 receptor (MC4R): A CNS GPCR activated by POMC-derived peptides to reduce food intake and regulate body weight.

References

1. Dysfunction of the adhesion G protein-coupled receptor latrophilin 1 (ADGRL1/LPHN1) increases the risk of obesity. Signal Transduction and Targeted Therapy (2024).
2. Hypothalamic circuits regulating appetite and energy homeostasis: pathways to obesity. Disease Models & Mechanisms (2017).
3. Genetically and functionally defined NTS to PBN brain circuits mediating anorexia. Nature Communications (2016).
4. α-Tanycytes of the adult hypothalamic third ventricle include distinct populations of FGF-responsive neural progenitors. Nature Communications (2013).
5. Evaluation of a melanocortin-4 receptor (MC4R) agonist (Setmelanotide) in MC4R deficiency. Molecular Metabolism (2017).
6. Whole-brain mapping of the direct inputs and axonal projections of POMC and AgRP neurons. Frontiers in Neuroanatomy (2015).