Medical Physiology

Leptin is a peptide hormone secreted by adipose cells, which plays a role in energy homeostasis. In a well-fed state, adipose fat stores increase, which causes leptin secretion to increase. The total amount of leptin secreted by the body increases as total fat mass increases.

Leptin has the following effects within the hypothalamus:
• Inhibits the lateral area, which controls hunger
• Stimulates the ventromedial area, which controls satiety

Leptin maintains energy homeostasis in response to high fat levels through the following effects:
• Decreases food intake
• Increases metabolic rate, activity level, and temperature
• Inhibits synthesis and release of insulin

Loss-of-function mutations in the leptin gene leads to early-onset, severe obesity.

Sleep deprivation leads to a decrease in leptin production.

Ghrelin is a peptide hormone secreted primarily by the P/D1 cells in the fundus of the stomach, as well as epsilon cells of the endocrine pancreas (small amount). Ghrelin is involved in energy homeostasis, and has effects antagonistic to those of leptin.

Ghrelin stimulates ‘food seeking’ behavior (orexigenic effect) through activation of the arcuate nucleus of the hypothalamus, and the vagus nerve of the parasympathetic nervous system.

Ghrelin levels drop shortly after a meal, and increase before a meal and during a period of fasting.

Ghrelin increases the secretion of:
• Growth hormone (via the growth hormone secretagogue receptor)
• Cortisol
• ACTH
• Prolactin

Gastric bypass surgery will result in a decreased ghrelin level.

Clinical Correlate: In Prader-Willi patients, ghrelin levels do not decrease after a meal. This leads to continuous food-seeking and subsequent weight gain.

Endocannabinoids are lipid ligands that bind to cannabinoid receptors and stimulate cortical reward centers, thereby stimulating desire for foods that are high in fat.

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