Thioredoxin Interacting Protein Is Required for a Chronic Energy-Rich Diet to Promote Intestinal Fructose Absorption
Anu Shah,
Sezin Dagdeviren,
Jordan P. Lewandowski,
Angela B. Schmider,
Elisabeth M. Ricci-Blair,
Niranjana Natarajan,
Henna Hundal,
Hye Lim Noh,
Randall H. Friedline,
Charles Vidoudez,
Jason K. Kim,
Amy J. Wagers,
Roy J. Soberman,
Richard T. Lee
Affiliations
Anu Shah
Department of Stem Cell and Regenerative Biology and the Harvard Stem Cell Institute, Harvard University, Sherman Fairchild Biochemistry Building, 7 Divinity Avenue, Cambridge, MA 02138, USA
Sezin Dagdeviren
Department of Stem Cell and Regenerative Biology and the Harvard Stem Cell Institute, Harvard University, Sherman Fairchild Biochemistry Building, 7 Divinity Avenue, Cambridge, MA 02138, USA
Jordan P. Lewandowski
Department of Stem Cell and Regenerative Biology and the Harvard Stem Cell Institute, Harvard University, Sherman Fairchild Biochemistry Building, 7 Divinity Avenue, Cambridge, MA 02138, USA
Angela B. Schmider
Molecular Imaging Core and Nephrology Division, Department of Medicine, Massachusetts General Hospital, Charlestown, MA 02129, USA
Elisabeth M. Ricci-Blair
Department of Stem Cell and Regenerative Biology and the Harvard Stem Cell Institute, Harvard University, Sherman Fairchild Biochemistry Building, 7 Divinity Avenue, Cambridge, MA 02138, USA
Niranjana Natarajan
Department of Stem Cell and Regenerative Biology and the Harvard Stem Cell Institute, Harvard University, Sherman Fairchild Biochemistry Building, 7 Divinity Avenue, Cambridge, MA 02138, USA
Henna Hundal
Department of Stem Cell and Regenerative Biology and the Harvard Stem Cell Institute, Harvard University, Sherman Fairchild Biochemistry Building, 7 Divinity Avenue, Cambridge, MA 02138, USA
Hye Lim Noh
Program in Molecular Medicine, Department of Medicine, University of Massachusetts Medical School, Worcester, MA 01605, USA
Randall H. Friedline
Program in Molecular Medicine, Department of Medicine, University of Massachusetts Medical School, Worcester, MA 01605, USA
Charles Vidoudez
Small Molecule Mass Spectrometry, Harvard University, Cambridge, MA 02138, USA
Jason K. Kim
Program in Molecular Medicine, Department of Medicine, University of Massachusetts Medical School, Worcester, MA 01605, USA; Division of Endocrinology, Metabolism and Diabetes, Department of Medicine, University of Massachusetts Medical School, Worcester, MA 01605, USA
Amy J. Wagers
Department of Stem Cell and Regenerative Biology and the Harvard Stem Cell Institute, Harvard University, Sherman Fairchild Biochemistry Building, 7 Divinity Avenue, Cambridge, MA 02138, USA; Glenn Center for the Biology of Aging, Harvard Medical School, Boston, MA 02115, USA; Section on Islet Cell and Regenerative Biology, Joslin Diabetes Center, Boston, MA 02215, USA
Roy J. Soberman
Molecular Imaging Core and Nephrology Division, Department of Medicine, Massachusetts General Hospital, Charlestown, MA 02129, USA
Richard T. Lee
Department of Stem Cell and Regenerative Biology and the Harvard Stem Cell Institute, Harvard University, Sherman Fairchild Biochemistry Building, 7 Divinity Avenue, Cambridge, MA 02138, USA; Cardiovascular Division, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA; Corresponding author
Summary: Increased consumption of fats and added sugars has been associated with an increase in metabolic syndromes. Here we show that mice chronically fed an energy-rich diet (ERD) with high fat and moderate sucrose have enhanced the absorption of a gastrointestinal fructose load, and this required expression of the arrestin domain protein Txnip in the intestinal epithelial cells. ERD feeding induced gene and protein expression of Glut5, and this required the expression of Txnip. Furthermore, Txnip interacted with Rab11a, a small GTPase that facilitates the apical localization of Glut5. We also demonstrate that ERD promoted Txnip/Glut5 complexes in the apical intestinal epithelial cell. Our findings demonstrate that ERD facilitates fructose absorption through a Txnip-dependent mechanism in the intestinal epithelial cell, suggesting that increased fructose absorption could potentially provide a mechanism for worsening of metabolic syndromes in the setting of a chronic ERD.
