We propose a model in which I148M and CGI-58 function at the nexus of two pathways critical for clearing hepatic TG – lipolysis and VLDL secretion – contributing to our understanding of how I148M increases risk for fatty liver disease.
Thank you to the co-authors and my postdoc mentor, Ray Deshaies!

Membrane fluidity is a biophysical property that is important for the biogenesis and secretion of VLDLs, which require substantial membrane deformations and changes along the secretory pathway. As a result of impaired VLDL secretion, TG builds up intracellularly in lipid droplets... Thread 🧵 4/5

ApoB is the main scaffolding protein found in all very low-density lipoprotein (VLDL) particles. We found that, through its sequestration of the lipolytic activator ABHD5/CGI-58, I148M causes a shift in cellular lipid composition that causes reduced membrane fluidity... Thread 🧵 3/5

However, it has proven challenging to elucidate the function of the wild-type protein and what goes awry with I148M to cause hepatic triglyceride (TG) accumulation.
Here, my colleagues and I show that liver cells expressing endogenous I148M have impaired secretion of ApoB...
Thread 🧵 2/5

Really inspiring talk! Thank you.