Liver fat gene
Coactivator sequestration by PNPLA3
Also searched as Coactivator sequestration by PNPLA3.
You want it low. It is a close relative of the rate-limiting lipase and competes for the same activator, soaking up the key without hydrolysing anything. A comMON human variant makes it worse: one widespread version captures the activator even more effectively and is strongly associated with fatty liver disease. That is how a decoy protein becomes a clinical problem.
In depth
A near-copy of the main lipase that captures its activator without doing any of the work.
What drives it
Lipid synthesis switch increases it.
PNPLA3 is a direct SREBP-1c target gene, strongly induced by feeding and insulin. doi 10.1186/s41021-022-00246-1
What it drives
It reduces Lipase activator.
The decoy. 'adiponutrin (also named as pnpla3), which is a close paralog of ATGL, has been demonstrated to compete with ATGL for binding to CGI58 and, in turn, effectively sequestering CGI58 from activating ATGL, thereby decreasing lipolysis' (doi 10.3389/fphys.2022.826314). The clinical edge: 'Genetic variations in the human PNPLA3 gene (the rs738409 I148M allele) have been strongly associated with fatty liver disease... PNPLA3-I148M suppresses the interaction of CGI58 with ATGL even more effectively.'. doi 10.3389/fphys.2022.826314
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.