Summary of project PR002594
This data is available at the NIH Common Fund's National Metabolomics Data Repository (NMDR) website, the Metabolomics Workbench, https://www.metabolomicsworkbench.org, where it has been assigned Project ID PR002594. The data can be accessed directly via it's Project DOI: 10.21228/M8BN8K This work is supported by NIH grant, U2C- DK119886.
See: https://www.metabolomicsworkbench.org/about/howtocite.php
| Project ID: | PR002594 |
| Project DOI: | doi: 10.21228/M8BN8K |
| Project Title: | Glycerol-3-phosphate activates ChREBP, FGF21 transcription and lipogenesis in Citrin Deficiency |
| Project Type: | MS quantitative analysis |
| Project Summary: | 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 do not like sweets. We discovered that SLC25A13 loss causes accumulation of glycerol-3-phosphate (G3P), which activates carbohydrate response element binding protein (ChREBP) to transcribe FGF21, which acts in the brain to restrain intake of sweets and alcohol, and to transcribe key genes of de novo lipogenesis. Mouse and human data establish G3P-ChREBP as a new mechanistic component of the Randle Cycle that contributes to metabolic dysfunction-associated steatotic liver disease (MASLD) and forms part of a system that communicates metabolic states from liver to brain in a manner that alters food and alcohol choices. The data provide a framework for understanding FGF21 induction in varied conditions, suggest ways to develop FGF21-inducing drugs, and drug candidates for both lean MASLD and support of urea cycle function in CD. |
| Institute: | Beckman Research Institute of City of Hope |
| Last Name: | Brenner |
| First Name: | Charles |
| Address: | 1500 E. Duarte Road, Duarte, California, 91010, USA |
| Email: | cbrenner@coh.org |
| Phone: | 626-218-2750 |
| Funding Source: | National Institute of Health grant R01HL147545 |
| Publications: | Tiwari, V. et al Glycerol-3-phosphate activates ChREBP, FGF21 transcription and lipogenesis in Citrin Deficiency doi: 10.1101/2024.12.27.630525 |
| Contributors: | Edwin Lopez Gonzalez, Vinod Tiwari and Olivia Sun |
Summary of all studies in project PR002594
| Study ID | Study Title | Species | Institute | Analysis(* : Contains Untargted data) | Release Date | Version | Samples | Download(* : Contains raw data) |
|---|---|---|---|---|---|---|---|---|
| ST004126 | Glyc3P, hexose phosphates, and pentose phosphates measurements in citrin deficiency. | Mus musculus | Beckman Research Institute of City of Hope | MS | 2025-08-21 | 1 | 35 | Uploaded data (690.3M)* |
