Circulating glycerate predicts resilience to fructose-induced hepatic steatosis
Year: 2025
Type: article
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.
Source: Cell Metabolism
Authors: Cuauhtemoc B. Ramirez, In Sook Ahn, Varvara I. Rubtsova, Ingrid Cely, Johnny Le, Joohwan Kim, Sunhee Jung, Miranda E. Kelly, Yeojin Kim, Hosung Bae, Won-Suk Song, Yasmine H. Alam, Guanglin Zhang, Graciel Diamante, Alina Chao, Lauren Hoffner, Alexis Anica, Izabelle Le, Miranda L. Lopez, Ian J. Tamburini, Elena M. Moyer, Ariel Tsai, Qin Yang, Xing Dai, Daniele Piomelli, Gina Lee, Xia Yang, Cholsoon Jang
Language: English
Subfield: Endocrinology, Diabetes and Metabolism
Field: Medicine
Domain: Health Sciences
Open Access status: hybrid
Estimated APC paid: $10,400
Funders: American Diabetes Association, Cancer Research Institute, Tuberous Sclerosis Alliance, National Research Foundation of Korea, National Institutes of Health, National Institute on Alcohol Abuse and Alcoholism, National Cancer Institute, National Institute of General Medical Sciences, National Institute of Diabetes and Digestive and Kidney Diseases
Awards: G1230067360, G1893372048, G2133017146, G2665618970, G3436779086, G363192923, G3786547764, Identify metabolite markers for diagnosis and treatment of TSC kidney tumor, G5364279705, G5709752925, Elucidating alcohol-induced metabolic remodeling of critical organs, Prevention and treatment of fructose-induced insulin resistance by dietary fibers, Systems Genetics Dissection of Non-alcoholic Steatohepatitis, Elucidating the role of nonessential amino acid metabolism in diabetic skin wounds, A Training Program for Interdisciplinary Cancer Research
OpenAlex ID: W4409654042