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

doi:10.1016/j.isci.2020.101521

Thioredoxin Interacting Protein Is Required for a Chronic Energy-Rich Diet to Promote Intestinal Fructose Absorption

iScience. 2020 Sep 2;23(9):101521. doi: 10.1016/j.isci.2020.101521. eCollection 2020 Sep 25.

Authors

Anu Shah¹, Sezin Dagdeviren¹, Jordan P Lewandowski¹, Angela B Schmider², Elisabeth M Ricci-Blair¹, Niranjana Natarajan¹, Henna Hundal¹, Hye Lim Noh³, Randall H Friedline³, Charles Vidoudez⁴, Jason K Kim^{3

5}, Amy J Wagers^{1

6

7}, Roy J Soberman², Richard T Lee^{1

8}

Affiliations

¹ 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.
² Molecular Imaging Core and Nephrology Division, Department of Medicine, Massachusetts General Hospital, Charlestown, MA 02129, USA.
³ Program in Molecular Medicine, Department of Medicine, University of Massachusetts Medical School, Worcester, MA 01605, USA.
⁴ Small Molecule Mass Spectrometry, Harvard University, Cambridge, MA 02138, USA.
⁵ Division of Endocrinology, Metabolism and Diabetes, Department of Medicine, University of Massachusetts Medical School, Worcester, MA 01605, USA.
⁶ Glenn Center for the Biology of Aging, Harvard Medical School, Boston, MA 02115, USA.
⁷ Section on Islet Cell and Regenerative Biology, Joslin Diabetes Center, Boston, MA 02215, USA.
⁸ Cardiovascular Division, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA.

Abstract

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.

Keywords: Human Metabolism; Molecular Biology.

Abstract

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