Diet-induced alteration of intestinal stem cell function underlies obesity and prediabetes in mice
Aliluev A, Tritschler S, Sterr M, Oppenlaender L, Hinterdobler J, Greisle T, Irmler M, Beckers J, Sun N, Walch A, Stemmer K, Kindt A, Krumsiek J, Tschop MH, Luecken MD, Theis FJ, Lickert H, Boettcher A (2021)
Publication Type: Journal article
Publication year: 2021
Journal
Book Volume: 3
Pages Range: 1202-1216
Journal Issue: 9
DOI: 10.1038/s42255-021-00458-9
Abstract
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.
Involved external institutions
Deutsches Zentrum für Diabetesforschung e.V. (DZD)
Germany (DE)
Helmholtz Zentrum München - Deutsches Forschungszentrum für Gesundheit und Umwelt (HMGU) / Helmholtz Munich
Germany (DE)
Germany (DE)
Helmholtz Zentrum München - Deutsches Forschungszentrum für Gesundheit und Umwelt (HMGU) / Helmholtz Munich
Germany (DE)
How to cite
APA:
Aliluev, A., Tritschler, S., Sterr, M., Oppenlaender, L., Hinterdobler, J., Greisle, T.,... Boettcher, A. (2021). Diet-induced alteration of intestinal stem cell function underlies obesity and prediabetes in mice. Nature Metabolism, 3(9), 1202-1216. https://doi.org/10.1038/s42255-021-00458-9
MLA:
Aliluev, Alexandra, et al. "Diet-induced alteration of intestinal stem cell function underlies obesity and prediabetes in mice." Nature Metabolism 3.9 (2021): 1202-1216.
BibTeX: Download