Cell metabolism · 2025
Circulating glycerate predicts resilience to fructose-induced hepatic steatosis.
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Ramirez Cuauhtemoc B, Ahn In Sook, Rubtsova Varvara I, Cely Ingrid, Le Johnny, Kim Joohwan, Jung Sunhee, Kelly Miranda E, Kim Yeojin, Bae Hosung, Song Won-Suk, Alam Yasmine H, Zhang Guanglin, Diamante Graciel, Chao Alina, Hoffner Lauren, Anica Alexis, Le Izabelle, Lopez Miranda L, Tamburini Ian J, Moyer Elena M, Tsai Ariel, Yang Qin, Dai Xing, Piomelli Daniele, Lee Gina, Yang Xia, Jang Cholsoon
Аннотация
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.