A high-fat diet induces a microbiota-dependent increase in stem cell activity in the Drosophila intestine

Autoři: Jakob von Frieling aff001;  Muhammed Naeem Faisal aff001;  Femke Sporn aff001;  Roxana Pfefferkorn aff001;  Stella Solveig Nolte aff001;  Felix Sommer aff002;  Philip Rosenstiel aff002;  Thomas Roeder aff001
Působiště autorů: Zoological Institute, Department of Molecular Physiology, Kiel University, Kiel, Germany aff001;  IKMB, UKSH, Kiel University, Kiel, Germany aff002;  German Center for Lung Research, Airway Research Center North, Kiel, Germany aff003
Vyšlo v časopise: A high-fat diet induces a microbiota-dependent increase in stem cell activity in the Drosophila intestine. PLoS Genet 16(5): e32767. doi:10.1371/journal.pgen.1008789
Kategorie: Research Article
doi: 10.1371/journal.pgen.1008789


Over-consumption of high-fat diets (HFDs) is associated with several pathologies. Although the intestine is the organ that comes into direct contact with all diet components, the impact of HFD has mostly been studied in organs that are linked to obesity and obesity related disorders. We used Drosophila as a simple model to disentangle the effects of a HFD on the intestinal structure and physiology from the plethora of other effects caused by this nutritional intervention. Here, we show that a HFD, composed of triglycerides with saturated fatty acids, triggers activation of intestinal stem cells in the Drosophila midgut. This stem cell activation was transient and dependent on the presence of an intestinal microbiota, as it was completely absent in germ free animals. Moreover, major components of the signal transduction pathway have been elucidated. Here, JNK (basket) in enterocytes was necessary to trigger synthesis of the cytokine upd3 in these cells. This ligand in turn activated the JAK/STAT pathway in intestinal stem cells. Chronic subjection to a HFD markedly altered both the microbiota composition and the bacterial load. Although HFD-induced stem cell activity was transient, long-lasting changes to the cellular composition, including a substantial increase in the number of enteroendocrine cells, were observed. Taken together, a HFD enhances stem cell activity in the Drosophila gut and this effect is completely reliant on the indigenous microbiota and also dependent on JNK signaling within intestinal enterocytes.

Klíčová slova:

Bacteria – c-Jun N-terminal kinase signaling cascade – Diet – Drosophila melanogaster – Fatty acids – Gastrointestinal tract – Microbiome – Quantitative analysis


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