Tutkijat tunnistivat hormonin (lontooksi cholesin), jonka eritys suolistossa lisääntyy vasteena kolesterolin imeytymiselle ruuasta. Tämä hormoni estää kolesterolisynteesiä maksassa ylläpitäen näin kolesterolin homeostaasia.
A gut-derived hormone regulates cholesterol metabolism
Highlights
•Cholesin is a cholesterol-induced gut hormone
•Cholesin regulates plasma cholesterol levels in both human and mouse
•Cholesin inhibits PKA-ERK1/2 signaling via binding to GPR146
•Cholesin suppresses SREBP2-controlled cholesterol synthesis in the liver
Abstract
The reciprocal coordination between cholesterol absorption in the intestine and de novo cholesterol synthesis in the liver is essential for maintaining cholesterol homeostasis, yet the mechanisms governing the opposing regulation of these processes remain poorly understood. Here, we identify a hormone, Cholesin, which is capable of inhibiting cholesterol synthesis in the liver, leading to a reduction in circulating cholesterol levels. Cholesin is encoded by a gene with a previously unknown function (C7orf50 in humans; 3110082I17Rik in mice). It is secreted from the intestine in response to cholesterol absorption and binds to GPR146, an orphan G-protein-coupled receptor, exerting antagonistic downstream effects by inhibiting PKA signaling and thereby suppressing SREBP2-controlled cholesterol synthesis in the liver. Therefore, our results demonstrate that the Cholesin-GPR146 axis mediates the inhibitory effect of intestinal cholesterol absorption on hepatic cholesterol synthesis. This discovered hormone, Cholesin, holds promise as an effective agent in combating hypercholesterolemia and atherosclerosis.
Rekisteröidy
Kirjaudu sisään
UKK
Etsi
