I don't know any expert people in the NAD field who are convinced that P7C3 compounds are NAMPT activators

happy to announce that i have post-doc openings for mid-2016 to advance this science

please read our work, think about the most exciting questions & approaches, & be in touch for an interview

note that there are now human data in support of our model
www.medrxiv.org/content/10.6...

Glycerol-3-phosphate activates ChREBP, FGF21 transcription and lipogenesis in citrin deficiency - Nature Metabolism In a mouse model of the rare disease citrin deficiency, the authors discovered that the accumulation of glycerol-3-phosphate leads to ChREBP activation and FGF21 induction. The study identifies glycerol-3-phosphate as a ChREBP-activating ligand, which could resolve paradoxes of FGF21 expression and clarify the logic of lipogenic transcription.

RESEARCH |
@charlesmbrenner.bsky.social et al
@cityofhope.bsky.social

In citrin deficiency, accumulation of glycerol-3-phosphate leads to ChREBP activation and FGF21 induction🧪

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

thank you, Christian

thanks to @russgoodman.bsky.social @markhermanmd.bsky.social @cnspracklen.bsky.social

Vinod Tiwari, Olivia Sun and Edwin Lopez Gonzalez from my lab, Byungchang Jin in Russ's lab, Hardik Shah and others

heading to helsinki to join @keisakamoto.bsky.social @awartiovaara.bsky.social and others at tuesday's SWAN meeting:

healthy aging, mitochondrial disease, MASLD, rare disease and more!

pretty astonishing

@charlesmbrenner.bsky.social nice podcast with Drs Nadolsky

happy to say i got a completely routine email today requesting that i ad hoc on an april 2 study section

thank you, Paul

IMO the mystery is why more folks don't call BS when it is so plain to see and why editors continue to review papers from groups that are obfuscatory

Glycerol-3-phosphate activates ChREBP, FGF21 transcription and lipogenesis in Citrin Deficiency Citrin Deficiency (CD) is caused by inactivation of SLC25A13, a mitochondrial membrane protein required to move electrons from cytosolic NADH to the mitochondrial matrix in hepatocytes. People with CD...

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...

Glycerol-3-phosphate activates ChREBP, FGF21 transcription and lipogenesis in Citrin Deficiency Citrin Deficiency (CD) is caused by inactivation of SLC25A13, a mitochondrial membrane protein required to move electrons from cytosolic NADH to the mitochondrial matrix in hepatocytes. People with CD...

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...

jackson state really brings it

I’m celebrating tonight with my father in law, Jack Strominger, who is about to enjoy his 100th New Years!

He wants to know whether any other scientist has published in their 100th year. He’s proud to have a paper in the works. I told him you all would know! Please RT

a crude wooden menorah lit with 7 candles!

happy newyearsnukkah 🕎

may it be so again!

for some reason down a rabbit hole of mid-80s-mid 2000s discoveries (Leptin, Orexin, Growth Hormone production, cold receptor, p21 KO mouse, human iPSCs, etc) and realizing that they were all accepted less than two week after submission. Orexin in 4 days! Those were the days....

Just to add to the sad news on #chemsky right now: I've now had it confirmed to me that Martin Karplus died on Saturday.

white text on black "Poorly explain what you do for a job."

I convert tax dollars to pdfs

Glycerol-3-phosphate activates ChREBP, FGF21 transcription and lipogenesis in Citrin Deficiency Citrin Deficiency (CD) is caused by inactivation of SLC25A13, a mitochondrial membrane protein required to move electrons from cytosolic NADH to the mitochondrial matrix in hepatocytes. People with CD...

www.biorxiv.org/content/10.1...

Excited that we could be part of this collaboration with the Brenner lab identifying that G3P is the metabolite that ChREBP directly senses!

Glycerol-3-phosphate activates ChREBP, FGF21 transcription and lipogenesis in Citrin Deficiency www.biorxiv.org/content/10.1101/2024.12....

Glycerol-3-phosphate activates ChREBP, FGF21 transcription and lipogenesis in Citrin Deficiency Citrin Deficiency (CD) is caused by inactivation of SLC25A13, a mitochondrial membrane protein required to move electrons from cytosolic NADH to the mitochondrial matrix in hepatocytes. People with CD...

Glycerol-3-phosphate activates ChREBP, FGF21 transcription and lipogenesis in Citrin Deficiency www.biorxiv.org/content/10.1...