Circulating glycerate predicts resilience to fructose-induced hepatic steatosis
Excessive intake of dietary fructose increases the risk of metabolic-dysfunction-associated steatotic liver disease (MASLD), cirrhosis, and cancers. However, what host factors determine disease vulnerability is incompletely understood. Here, we leverage genetically divergent mouse strains, mass spectrometry-based metabolomics, and in vivo isotope tracing, identifying circulating glycerate as a biomarker that predicts resilience to fructose-induced hepatic steatosis in both sexes. We found that the surge of circulating glycerate after an oral fructose provision reflects strong small-intestinal fructose catabolism. Such fructose clearance by the small intestine is linked to a weaker induction of hepatic de novo lipogenesis and steatosis upon chronic fructose exposure across strains. These data indicate the potential utility of an oral fructose tolerance test and circulating glycerate measurements to predict an individual's susceptibility to fructose-elicited steatotic liver and provide personalized dietary recommendations.
Authors
- Hosung Bae (ORCID: https://orcid.org/0000-0001-5848-7972)
- Varvara I. Rubtsova (ORCID: https://orcid.org/0000-0003-3912-4820)
- Yasmine H. Alam
- Sunhee Jung (ORCID: https://orcid.org/0000-0001-5396-4813)
- Cholsoon Jang (ORCID: https://orcid.org/0000-0001-6651-4213)
- Daniele Piomelli (ORCID: https://orcid.org/0000-0002-2983-774X)
- Ingrid Cely
- Xing Dai (ORCID: https://orcid.org/0000-0001-8134-1365)
- Lauren Hoffner (ORCID: https://orcid.org/0000-0002-2861-9898)
- Graciel Diamante (ORCID: https://orcid.org/0000-0002-2433-6161)
- Joo‐Hwan Kim (ORCID: https://orcid.org/0000-0002-2999-4411)
- Gina Lee (ORCID: https://orcid.org/0000-0002-8120-9169)
- Yeojin Kim (ORCID: https://orcid.org/0009-0009-2647-7046)
- A. Chun-Hui Tsai
- Cuauhtemoc B. Ramirez (ORCID: https://orcid.org/0000-0001-7182-1859)
- Johnny Le (ORCID: https://orcid.org/0000-0002-0245-5848)
- Xia Yang (ORCID: https://orcid.org/0000-0002-3971-038X)
- Alexis Anica
- Guanglin Zhang (ORCID: https://orcid.org/0000-0001-7248-4874)
- Miranda Lopez
- Alina Chao
- Won-Suk Song
- In Sook Ahn
- M. Kelly
- Ian Tamburini
- Qin Yang (ORCID: https://orcid.org/0000-0003-3792-2116)
- Elena M. Moyer
Institutions
- University of California, Los Angeles (US)
- University of California, Irvine (US)
- Irvine University (US)
Publication Details
- Journal
- Cell Metabolism
- Published
- 2025-04-22
- DOI
- https://doi.org/10.1016/j.cmet.2025.03.017
- Citations
- 3
- Primary Topic
- Diet, Metabolism, and Disease
- Type
- article
- Field-Weighted Citation Impact
- 3.88