Satiety hormone sensitivity quantifies the responsiveness of the brain’s appetite centers, primarily in the hypothalamus, to circulating peptide hormones released by the gut and adipose tissue, such as leptin, ghrelin, and peptide YY (PYY). High sensitivity indicates an effective feedback loop where hormone signals accurately register fullness, leading to appropriate cessation of eating and maintenance of energy balance. Reduced sensitivity, or resistance, is a major physiological driver of hyperphagia and weight dysregulation.
Origin
This concept is rooted in neuroendocrinology, emerging from the discovery of leptin in the mid-1990s, which established the link between adipose tissue mass and hypothalamic appetite regulation. The term ‘sensitivity’ emphasizes that the clinical problem is often not a deficiency in the hormone itself but a failure of the target receptor to transduce the signal effectively. This is a key area of research in the pathology of obesity and metabolic syndrome.
Mechanism
The mechanism involves the binding of satiety hormones to their specific receptors on neurons within the arcuate nucleus of the hypothalamus, modulating the expression of appetite-regulating neuropeptides like pro-opiomelanocortin (POMC). When sensitivity is high, a small hormonal signal leads to a robust neural response that suppresses hunger and increases energy expenditure. Conversely, chronic overexposure to high levels of these hormones, such as hyperleptinemia, can lead to receptor downregulation and signal blunting, resulting in a state of functional resistance.
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