Hormonal
Leptin acts as an anorexigenic signal by binding to LEPRb in the hypothalamus, activating the JAK2/STAT3 and PI3K pathways to stimulate POMC and inhibit AgRP neurons, thereby reducing food intake and increasing energy expenditure.
Your body produces leptin to tell your brain you are full. In obesity, this signal often gets ignored (leptin resistance). You cannot simply 'take' leptin to fix this. Focus on strategies that may improve insulin sensitivity and reduce inflammation, which are linked to leptin signaling, rather than seeking leptin-based supplements which are ineffective for most.
Leptin binds to LEPRb and activates JAK2, which, in turn, phosphorylates several tyrosine residues on the intracellular domain of the LEPRb. This results in the activation, dimerization, and nuclear translocation of STAT3... In the nucleus, STAT3 enhances Pomc gene expression and inhibits Agrp gene expression... Leptin stimulates Pomc transcription, depolarizes POMC neurons, and also increases a-MSH processing and secretion... while attenuating the expression and release of orexigenic NPY and AGRP neuropeptides.
Why this rating
The paper cites extensive genetic, pharmacological, and electrophysiological evidence from multiple studies (knockout mice, human mutations) confirming the pathway.
Source
Hypothalamic and brainstem neuronal circuits controlling homeostatic energy balance
Marc Schneeberger et al. · Journal of Endocrinology · 2013
DOI 10.1530/joe-13-0398
More from this paper
- Ghrelin acts as an orexigenic signal by binding to GHSR on AgRP neurons in the arcuate nucleus, stimulating NPY and AGRP expression and increasing food intake and adiposity.Strong
- GLP1, secreted from intestinal L-cells after meals, acts as an anorexigenic signal by activating GLP1 receptors in the hypothalamus and brainstem, inhibiting food intake via vagal afferents and central circuits.Strong
- Insulin acts as an anorexigenic signal in the CNS by binding to insulin receptors in the hypothalamus, activating PI3K signaling to inhibit NPY and stimulate POMC, thereby reducing food intake.Good
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