Natriuretic clearance receptor
Natriuretic peptide receptor C (NPR-C)↓
Also searched as Natriuretic peptide receptor C (NPR-C).
Two receptors answer the same hormone. One does the work; the other exists only to clear the hormone away. What matters is the ratio between them — and in people carrying more fat, the clearing one is more abundant, so the signal is blunted before it can act. That means the useful target on this road is the drain, not the hormone: raising a hormone into a widened drain achieves less than narrowing the drain would. The machinery is weakest exactly where it is most needed.
In depth
The receptor that removes the heart's fat-release hormone from circulation — and it is more abundant in obesity.
What drives it
Heart-derived pressure hormone increases it.
ANP and BNP are the ligands bound and internalized by the NPR-C clearance receptor. PMID 7631865
What it drives
It reduces Heart-derived pressure hormone.
The second road has a drain, and it is wider in exactly the people who need the road. There are two receptors for the heart's fat-release hormones: one does the work, the other simply removes the hormone from circulation. 'the ability of the NPs to elicit a biological response depends on the relative ratio of the functional receptor npra to the clearance receptor nprc' (pmc7418652 — Enhancing natriuretic peptide signaling in adipose tissue, but not in muscle, protects against diet-induced obesity). And the ratio is unfavourable in obesity: 'compared with lean individuals, obese subjects have increased NPRC abundance in adipose tissues, resulting in a decreased NPRA/NPRC ratio and blunted cellular responses' (pmc7418652 — Enhancing natriuretic peptide signaling in adipose tissue, but not in muscle, protects against diet-induced obesity, and confirmed independently in pmc5067565 — Adipose tissue natriuretic peptide receptor expression is related to insulin sensitivity in obesity and diabetes). ⇒ the target worth reaching on this road is not the hormone. It is the drain. Raising the hormone into a widened drain achieves less than narrowing the drain would. This is the same shape as the finding that the first lipase is depleted in obesity: the machinery is weakest precisely where it is most needed.
It reduces Releases stored fat.
The second road has a drain, and it is wider in exactly the people who need the road. There are two receptors for the heart's fat-release hormones: one does the work, the other simply removes the hormone from circulation. 'the ability of the NPs to elicit a biological response depends on the relative ratio of the functional receptor npra to the clearance receptor nprc' (pmc7418652 — Enhancing natriuretic peptide signaling in adipose tissue, but not in muscle, protects against diet-induced obesity). And the ratio is unfavourable in obesity: 'compared with lean individuals, obese subjects have increased NPRC abundance in adipose tissues, resulting in a decreased NPRA/NPRC ratio and blunted cellular responses' (pmc7418652 — Enhancing natriuretic peptide signaling in adipose tissue, but not in muscle, protects against diet-induced obesity, and confirmed independently in pmc5067565 — Adipose tissue natriuretic peptide receptor expression is related to insulin sensitivity in obesity and diabetes). ⇒ the target worth reaching on this road is not the hormone. It is the drain. Raising the hormone into a widened drain achieves less than narrowing the drain would. This is the same shape as the finding that the first lipase is depleted in obesity: the machinery is weakest precisely where it is most needed.
Blends that modulate it
Each blend page names this pathway and carries the study behind its claim.
See it on the map
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