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Aliluev, A. ; Tritschler, S. ; Sterr, M. ; Oppenländer, L. ; Hinterdobler, J. ; Greisle, T. ; Irmler, M. ; Beckers, J. ; Sun, N. ; Walch, A.K. ; Stemmer, K. ; Kindt, A. ; Krumsiek, J. ; Tschöp, M.H. ; Luecken, M. ; Theis, F.J. ; Lickert, H. ; Böttcher, A.

Diet-induced alteration of intestinal stem cell function underlies obesity and prediabetes in mice.

Nat. Metab. 3, 1202-1216 (2021)
Verlagsversion DOI PMC
Open Access Gold (Paid Option)
Creative Commons Lizenzvertrag
Excess nutrient uptake and altered hormone secretion in the gut contribute to a systemic energy imbalance, which causes obesity and an increased risk of type 2 diabetes and colorectal cancer. This functional maladaptation is thought to emerge at the level of the intestinal stem cells (ISCs). However, it is not clear how an obesogenic diet affects ISC identity and fate. Here we show that an obesogenic diet induces ISC and progenitor hyperproliferation, enhances ISC differentiation and cell turnover and changes the regional identities of ISCs and enterocytes in mice. Single-cell resolution of the enteroendocrine lineage reveals an increase in progenitors and peptidergic enteroendocrine cell types and a decrease in serotonergic enteroendocrine cell types. Mechanistically, we link increased fatty acid synthesis, Ppar signaling and the Insr-Igf1r-Akt pathway to mucosal changes. This study describes molecular mechanisms of diet-induced intestinal maladaptation that promote obesity and therefore underlie the pathogenesis of the metabolic syndrome and associated complications.
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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Korrespondenzautor
Schlagwörter Insulin-resistance; Bariatric Surgery; Wnt/beta-catenin; Homeostasis; Glucose; Differentiation; Proliferation; Metabolism; Physiology; Secretion
ISSN (print) / ISBN 2522-5812
e-ISSN 2522-5812
Zeitschrift Nature metabolism
Quellenangaben Band: 3, Heft: 9, Seiten: 1202-1216 Artikelnummer: , Supplement: ,
Verlag Springer
Verlagsort London
Nichtpatentliteratur Publikationen
Begutachtungsstatus Peer reviewed
Institut(e) Institute of Computational Biology (ICB)
Institute of Diabetes and Regeneration Research (IDR)
Institute of Experimental Genetics (IEG)
Research Unit Analytical Pathology (AAP)
Institute of Diabetes and Obesity (IDO)