Research
Hormonal
LEAP2 acts as a GHSR antagonist that hyperpolarizes arcuate NPY neurons and prevents acyl-ghrelin from activating them, thereby blunting ghrelin's orexigenic effects.
This is a deep biological mechanism showing how your brain processes hunger signals. LEAP2 physically blocks the hunger signal at the neuronal level. This explains why high levels of LEAP2 in obesity might contribute to 'ghrelin resistance,' where the hunger signal is less effective.
StrongSupportsVERY_HIGH confidence
We showed that LEAP2 both hyperpolarizes and prevents acyl-ghrelin from activating arcuate NPY neurons.
Why this rating
Direct electrophysiological evidence (patch-clamp) provides high-fidelity mechanistic data.
Source
LEAP2 changes with body mass and food intake in humans and mice
Bharath K. Mani et al. · Journal of Clinical Investigation · 2019
DOI 10.1172/jci125332
cohortCited 205×
Read the paper DOI resolved against Crossref · corpus check 2026-06-10
More from this paper
- Plasma LEAP2 levels increase with higher body mass, obesity, and postprandial states in humans and mice, acting as an endogenous antagonist to acyl-ghrelin to limit food intake and blood glucose elevation.Good
- Bariatric surgeries, specifically Roux-en-Y gastric bypass (RYGB) and vertical sleeve gastrectomy (VSG), reduce fasting plasma LEAP2 levels in humans with obesity, correlating with weight loss and improved metabolic markers.Good
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