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Cell Metab., April 22, 2025 | https://doi.org/10.1016/j.cmet.2025.03.017
Circulating glycerate predicts resilience to fructose-induced hepatic steatosis
Cuauhtemoc B. Ramirez,1,2,9 In Sook Ahn,3,9 Varvara I. Rubtsova,1,2,10 Ingrid Cely,3,10 Johnny Le,1 Joohwan Kim,2 Sunhee Jung,1 Miranda E. Kelly,1 Yeojin Kim,1 Hosung Bae,1 Won-Suk Song,1 Yasmine H. Alam,1 Guanglin Zhang,3 Graciel Diamante,3 Alina Chao,1 Lauren Hoffner,1,2 Alexis Anica,1,2 Izabelle Le,1,2 Miranda L. Lopez,1 Ian J. Tamburini,1 Elena M. Moyer,1 Ariel Tsai,1 Qin Yang,4 Xing Dai,1 Daniele Piomelli,1,5,6 Gina Lee,2,7,8,* Xia Yang,3,* and Cholsoon Jang 1,7,8,11,*
1Department of Biological Chemistry, University of California, Irvine, Irvine, CA, USA
2Department of Microbiology and Molecular Genetics, University of California, Irvine, Irvine, CA, USA
3Department of Integrative Biology and Physiology, University of California, Los Angeles, Los Angeles, CA, USA
4Department of Physiology and Biophysics, University of California, Irvine, Irvine, CA, USA
5Department of Anatomy and Neurobiology, University of California, Irvine, Irvine, CA, USA
6Department of Pharmaceutical Sciences, University of California, Irvine, Irvine, CA, USA
7Chao Family Comprehensive Cancer Center, University of California, Irvine, Irvine, CA, USA
8Center for Epigenetics and Metabolism, University of California, Irvine, Irvine, CA, USA
9These authors contributed equally
10These authors contributed equally
11Lead contact
2Department of Microbiology and Molecular Genetics, University of California, Irvine, Irvine, CA, USA
3Department of Integrative Biology and Physiology, University of California, Los Angeles, Los Angeles, CA, USA
4Department of Physiology and Biophysics, University of California, Irvine, Irvine, CA, USA
5Department of Anatomy and Neurobiology, University of California, Irvine, Irvine, CA, USA
6Department of Pharmaceutical Sciences, University of California, Irvine, Irvine, CA, USA
7Chao Family Comprehensive Cancer Center, University of California, Irvine, Irvine, CA, USA
8Center for Epigenetics and Metabolism, University of California, Irvine, Irvine, CA, USA
9These authors contributed equally
10These authors contributed equally
11Lead contact
*Corresponding authors: correspondence to Gina Lee, Xia Yang or Cholsoon Jang
Abstract
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.
논문정보
- Research article
- 2025년 04월 (BRIC 등록일 2025-04-24)
- 국외 연구진
- 생명과학 > 생화학
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