We are pleased to announce the publication in Nature Metabolism titled “Glycerol-3-phosphate activates ChREBP, FGF21 transcription and lipogenesis in citrin deficiency”, authored by Vinod Tiwari (first author) and Charles Brenner (senior author) at the Beckman Research Institute of City of Hope. You may read the full publication here: https://doi.org/10.1038/s42255-025-01399-3
This study proposes a mechanistic explanation for carbohydrate aversion and fatty liver observed in citrin deficiency (CD) patients. Using a CD mouse and complementary cellular systems, the authors observe the accumulation of glycerol-3-phosphate (G3P) that could activate the carbohydrate response element-binding protein (ChREBP) transcriptional program and upregulate fibroblast growth factor 21 (Fgf21). They propose that this signaling mechanism acts in the brain for dietary aversion behavior and induces lipogenesis. Based on these findings, the authors suggest potential ways to develop drugs for lean metabolic-dysfunction-associated steatotic liver disease (MASLD) and CD.
The Foundation is pleased to have introduced the unique research questions surrounding CD to the group and to have provided the specific mouse model that made this work possible. This work illustrates how studying CD, which causes the inactivation of the malate-aspartate shuttle, a fundamental metabolic pathway, can yield broader insights with implications beyond the condition itself. We warmly congratulate the authors on this impactful contribution to our understanding of CD.
