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Targeting colonic macrophages as a potential therapeutic option in metabolic disease

Rohm, Theresa. Targeting colonic macrophages as a potential therapeutic option in metabolic disease. 2020, Doctoral Thesis, University of Basel, Faculty of Science.

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Official URL: http://edoc.unibas.ch/diss/DissB_13634

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Abstract

Obesity is characterized by chronic low-grade inflammation. However, the initiating mechanisms remain poorly understood. Here, we characterized intestinal macrophage subpopulations and their role in high-fat diet (HFD)-induced obesity in mice and humans. Pro-inflammatory/monocyte-derived intestinal macrophages transiently increased upon food intake and became chronically elevated upon HFD, suggesting a link between macrophage numbers and glycemia. Indeed, pharmacological dose-dependent or genetic ablation of macrophages improved glucose homeostasis. In particular, colon-specific macrophage depletion improved glycemic control and ameliorated β-cell function. Intestinal macrophage activation upon HFD was characterized by a strong interferon signature and metabolic shift, potentially via mTOR activation. Accordingly, colon-specific mTOR-inhibition enhanced insulin and GLP-1 secretion. In obese humans, pro-inflammatory intestinal macrophages were also increased, potentially by enhanced monocyte recruitment. Taken together, these data reveal that intestinal innate immunity contributes to glycemic dysfunction in obesity. Therefore, specifically targeting colonic macrophages or their activation might be a novel therapeutic avenue to improve glycemic control.
Advisors:Hess, Christoph and Christofori, Gerhard M.
Faculties and Departments:03 Faculty of Medicine > Departement Biomedizin > Department of Biomedicine, University Hospital Basel > Immunobiology (Hess C)
05 Faculty of Science
UniBasel Contributors:Hess, Christoph and Christofori, Gerhard M.
Item Type:Thesis
Thesis Subtype:Doctoral Thesis
Thesis no:13634
Thesis status:Complete
Bibsysno:Link to catalogue
Number of Pages:1 Online-Ressource (113 Blätter)
Language:English
Identification Number:
Last Modified:12 Aug 2020 04:30
Deposited On:11 Aug 2020 12:28

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