The Anchor
You want it low, and the genetics are unusually consistent. It is required for the stability of the lectin that sits on the droplet suppressing release; without it that lectin is destroyed in the lysosome. Deleting it in both white and brown fat raises release, both at baseline and under adrenaline, apparently because the rate-limiting lipase reaches the droplet more easily. The source is honest that the order of causation between the two proteins is not yet settled.
In depth
The protein that keeps the droplet gatekeeper stable — remove it and the gatekeeper degrades.
What drives it
Fat-cell formation↓ increases it.
VPS13C expression rises during adipocyte differentiation, where it supports lipid-droplet maturation. PMID 27073999
What it drives
It increases The Droplet Gatekeeper.
'VACUOLAR protein sorting 13C (VPS13C), a novel lipid droplet protein, was identified as a major GALECTIN12-binding protein that is required for GALECTIN12 protein stability. Consistently, knockdown of VPS13C leaded to GALECTIN12 degradation primarily through the lysosomal pathway'. doi 10.3389/fphys.2022.826314
It reduces Releases stored fat.
'deletion of vps13c in brown and white adipocytes augments basal and beta-adrenergic-induced lipolysis, likely due to enhanced ATGL trafficking to lipid dropletS' (doi 10.3389/fphys.2022.826314). The source leaves the causal order open: 'It will be of interest to explore whether the impact of VPS13C loss on lipolysis depends on GALECTIN12 OR VICE VERSA.'. 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.