we also see an integrated stress response in the mouse model of this dz, which looks to exascerbate urea cycle function, & GWAS signal suggesting that SLC25A13 carriers have elevated FGF21

tx to all authors, funding agencies, Dr. Saheki &
@citrinfdn
for inspiration & support🙏

our diagrams create a framework for solving the paradoxes of FGF21 (eg both ketogenic diet & simple carbs turn it on)... converging on G3P-ChREBP as the activator

same system depresses expression & activity of CPT1A, which explains why MCT can be burned but the TGs in their livers & dietary TGs aren't burned

i hypothesized that their livers are under a stress in which they make FGF21 bc this would account for the sweet aversion

in this paper we discovered that G3P turns on ChREBP not only to turn on FGF21 but to create the fatty liver

they have fatty liver despite being overall lean, they can have outbreaks of urea cycle toxicity, they are predisposed to liver cancer & they don't like sweets

CD is a rare dz that disrupts SLC25A13 gene. in 1st month of life, pts present w liver problems: retaining bile, exporting lactate & not running urea cycle

after genetic diagnosis, their diet is modified to low carb, low protein, high MCT oil & they can grow to adulthood but...

our work on citrin deficiency (CD) revealed G3P as the ChREBP activator, created a framework to explain FGF21 induction in a wide variety of conditions, accounts for the beneficial effect of MCTs in CD, why urea cycle dysfunction is so severe in CD and more

Congrats on this exciting new work! Uncovering how glycerol-3-phosphate activates ChREBP, FGF21, and lipogenesis in Citrin Deficiency adds valuable insight to metabolic regulation. Looking forward to seeing how this advances the field! 🚀🧬👏

pretty astonishing

The doi segment of the first link in the thread's url was cutoff; here's the link in its entirety: www.biorxiv.org/content/10.1...

The doi segment of the first link in the thread's url was cutoff; here's the link in its entirety: www.biorxiv.org/content/10.1...