Ghrelin Physiology and Its Role in Energy Homeostasis
Summary
Ghrelin is a 28-amino acid peptide hormone predominantly produced by specialised endocrine cells in the gastric mucosa and activated by post-translational n-octanoylation. As the natural ligand for the growth hormone secretagogue receptor (GHSR), ghrelin orchestrates a range of physiological processes central to energy homeostasis. In the hypothalamus, ghrelin engages arcuate nucleus circuits to stimulate orexigenic neuropeptide Y/agouti-related peptide neurones and modulate anorexigenic pro-opiomelanocortin signalling, thereby driving meal initiation. Beyond this classical axis, ghrelin crosses the blood–brain barrier to influence mesolimbic pathways, including ventral tegmental area dopamine release, linking metabolic state to reward evaluation and food-seeking behaviour. Peripheral actions encompass regulation of gastrointestinal motility, insulin secretion and lipid accumulation, while emerging evidence implicates ghrelin in glucose homoeostasis, sleep–wake rhythms and cardiovascular function. Secretion exhibits circadian oscillations and is tightly suppressed by nutrient intake, reflecting feedback integration with leptin and insulin. The dual central and peripheral reach of ghrelin renders it a critical mediator of short-term appetite control and long-term energy balance, making the ghrelin–GHSR system a promising target for interventions in obesity, cachexia and metabolic syndrome.
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Ghrelin Physiology and Its Role in Energy Homeostasis publication trend
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Technical terms
Ghrelin: A stomach-derived peptide hormone that stimulates appetite, growth hormone release and metabolic regulation.
Growth hormone secretagogue receptor (GHSR): A G protein-coupled receptor whose activation by acyl ghrelin mediates central and peripheral effects.
Energy homeostasis: The coordinated balance of energy intake, expenditure and storage to maintain physiological stability.
Acyl ghrelin: The bioactive form of ghrelin carrying an n-octanoyl fatty acid essential for receptor binding.
vS-NAc circuit: A neural pathway from the ventral hippocampus to the nucleus accumbens that modulates the decision to initiate feeding.
References
- Internal-state-dependent control of feeding behavior via hippocampal ghrelin signaling. Neuron (2023).
- GHSR blockade, but not reduction of peripherally circulating ghrelin via β1-adrenergic receptor antagonism, decreases binge-like alcohol drinking in mice. Molecular Psychiatry (2024).
- A randomized controlled experimental medicine study of ghrelin in value-based decision making. Journal of Clinical Investigation (2023).
- Structure and Physiological Actions of Ghrelin. Scientifica (2013).
- Ghrelin Acts as an Interface between Physiological State and Phasic Dopamine Signaling. Journal of Neuroscience (2014).
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