Research
Hormonal
Obesity results from dysregulation of the hypothalamic melanocortin system, where antagonists like AgRP block the anorexic effects of insulin and leptin.
Your brain has a 'thermostat' for fat (melanocortin system). If this system is disrupted (genetically or by obesity itself), your brain fights weight loss. Understanding this helps explain why dieting is hard and why medical interventions targeting this system can be effective.
StrongSupportsVERY_HIGH confidence
The melanocortin system projects to multiple areas in the brain... POMC-expressing neurons in the ARC express receptors for adiposity signals (e.g., leptin)... Leptin and insulin also function to reduce NPY and AgRP expression.
Why this rating
Strong genetic and pharmacological evidence cited (knockout mice, receptor antagonists).
Source
Insulin and Leptin as Adiposity Signals
S.C. Benoit · Recent Progress in Hormone Research · 2004
DOI 10.1210/rp.59.1.267
narrative_reviewCited 264×
Read the paper DOI resolved against Crossref · corpus check 2026-06-10
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