Journal article
Intestinal fructose catabolism promotes obesity and insulin resistance via ileal lacteal remodeling
Science advances, Vol.12(35), eaec0481
08/28/2026
DOI: 10.1126/sciadv.aec0481
PMID: 42664326
Abstract
High-fructose corn syrup (HFCS) consumption is a risk factor for obesity and diabetes, yet the underlying mechanisms, especially at the specific organ level, are incompletely understood. Catabolism of dietary fructose primarily occurs in the small intestine and liver, with fructose breakdown in the liver being pathological, while small intestinal fructose clearance protects the liver. Here, we report that inhibition of fructose catabolism specifically in the murine small intestine unexpectedly mitigates fructose-induced obesity and insulin resistance. Such phenotypes are attributed to decreased dietary fat absorption by the shortening of ileal lacteals. Fecal transplantation experiments revealed that the microbiome altered by blunted host intestinal fructose catabolism decreases ileal macrophages essential for lacteal growth. Thus, altered intestinal lacteal architecture likely contributes to the synergistic effects of high fat and sugar on metabolic disorders. It may also be relevant to the clinical evidence that pharmacologic suppression of fructose catabolism mitigates diet-induced obesity.
Details
- Title: Subtitle
- Intestinal fructose catabolism promotes obesity and insulin resistance via ileal lacteal remodeling
- Creators
- Miranda L Lopez - University of California, IrvineTaekyung Kang - University of California, IrvineAna M Espeleta - University of California, IrvineVarvara I Rubtsova - University of California, IrvineJongwon Baek - University of California, IrvineJakob Songcuan - University of California, IrvineElena M Moyer - University of California, IrvineJoohwan Kim - University of California, IrvineWon-Suk Song - University of California, IrvineSunhee Jung - University of California, IrvineRochelle W Lai - University of California, Los AngelesAiyana Binuya - University of California, IrvineChristopher H Lee - University of California, IrvineAmy R Lantz - University of California, IrvineNicholas D'Sa - University of California, IrvineAlexis Anica - University of California, IrvineElise Tran - University of California, IrvineYujin Chun - University of California, IrvineWonsuk Choi - University of California, IrvineKi-Hong Jang - University of California, IrvineSungji Cho - University of California, IrvineMiranda E Kelly - University of California, IrvineIan J Tamburini - University of California, IrvineYasmine H Alam - University of California, IrvineJohnny Le - University of California, IrvineCuauhtemoc B Ramirez - University of California, IrvineRaghu P Kataru - Memorial Sloan Kettering Cancer CenterSeon Pyo Hong - Institute for Basic ScienceThomas Q de Aguiar Vallim - University of California, Los AngelesDequina A Nicholas - University of California, IrvineKatherine S Xue - University of California, IrvineGina Lee - University of California, IrvineHosung Bae - University of IowaCholsoon Jang - University of California, Irvine
- Resource Type
- Journal article
- Publication Details
- Science advances, Vol.12(35), eaec0481
- DOI
- 10.1126/sciadv.aec0481
- PMID
- 42664326
- NLM abbreviation
- Sci Adv
- ISSN
- 2375-2548
- eISSN
- 2375-2548
- Publisher
- American Association for the Advancement of Science
- Grant note
- T32 GM136624 / NIGMS NIH HHS R01 AA029124 / NIAAA NIH HHS R21 AA030358 / NIAAA NIH HHS P30 DK063491 / NIDDK NIH HHS
- Language
- English
- Date published
- 08/28/2026
- Academic Unit
- Internal Medicine
- Record Identifier
- 9985221947702771
Metrics
5 Record Views