The Second Padlock
You want it low, and its existence raises a question the field has not answered. It inhibits the same lipase by the same direct binding, only less potently — and nobody knows why the cell keeps two. The current guess is that they guard different droplets. It also works both ends: independently of the lipase, it drives the enzyme that puts fat back. It slows the emptying and speeds the refilling.
In depth
A hypoxia-driven protein that binds the rate-limiting lipase and shuts it, alongside the first padlock.
What drives it
Hypoxia response increases it.
HILPDA, the hypoxia-inducible lipid-droplet-associated protein, is a direct HIF-1alpha target gene. PMID 20624928
What it drives
It reduces Fat-releasing enzyme (ATGL).
'hilpda, also known as hypoxia-induced gene-2, inhibits ATGL activity through direct physical interaction as well, even though with a lower inhibitory potency tHAN G0S2' (doi 10.3389/fphys.2022.826314). An open question the source admits: 'the reasons for being equipped with two similar, endogenous ATGL inhibitors are unclear.' and it works both ends: 'independently of its effects on ATGL, HILPDA also stimulates DGAT1-mediated triglyceride synthesis.'. doi 10.3389/fphys.2022.826314
See it on the map
Open the causal map to follow this pathway upstream and downstream, arrow by arrow, each with its study.