Heart-derived pressure hormone
Natriuretic peptide-cGMP signaling
Also searched as Natriuretic peptide-cGMP signaling.
You want this route intact because it is independent of adrenaline. It reaches the same two guard proteins through a different second messenger and a different kinase, so it still works when the adrenaline arm is blunted — which matters, because that arm is measurably blunted in obesity. These are cardiac hormones; anything claiming to move them is making a cardiovascular claim, not only a fat-loss one.
In depth
Heart-derived peptides that open the same fat droplet through a completely different messenger — cGMP rather than cAMP.
What drives it
Natriuretic clearance receptor reduces it.
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.
What it drives
It increases Releases stored fat.
10.1017/s0029665109990279 — a second, fully independent trigger — different messenger, different kinase, same targets. 'Natriuretic peptides promote cGMP accumulation and PKG activation via type A receptor. PKA and PKG phosphorylate hormone-sensitive lipase (HSL) and perilipin A (PLINA)' (Proc Nutr Soc). And on division of labor between the lipases: 'Hormone-sensitive lipase appears as the major lipase for catecholamine and natriuretic peptide-stimulated lipolysis whereas adipose triglyceride lipase mediates the hydrolysis of triglycerides during basal lipolysis.' These are cardiac hormones. doi 10.1017/s0029665109990279
It increases Natriuretic receptor.
'atrial natriuretic peptide (ANP) binds to natriuretic peptide receptor A (NPR-A), leading to the activation of the guanylyl cyclase (GC) domain of NPR-A and the rise of cyclic guanine MONOPHOSPHATE (cGMP) levels'. doi 10.1242/jeb.165381 · PMID 29514884
It increases Natriuretic clearance receptor.
ANP and BNP are the ligands bound and internalized by the NPR-C clearance receptor. PMID 7631865
Blends that modulate it
Each blend page names this pathway and carries the study behind its claim.
See it on the map
Open the causal map to follow this pathway upstream and downstream, arrow by arrow, each with its study.