Rohm, Theresa V; Keller, Lena; Bosch, Angela J T; AlAsfoor, Shefaa; Baumann, Zora; Thomas, Amandine; Wiedemann, Sophia J; Steiger, Laura; Dalmas, Elise; Wehner, Josua; Rachid, Leila; Mooser, Catherine; Yilmaz, Bahtiyar; Fernandez Trigo, Nerea; Jauch, Annaise J; Wueest, Stephan; Konrad, Daniel; Henri, Sandrine; Niess, Jan H; Hruz, Petr; ... (2022). Targeting colonic macrophages improves glycemic control in high-fat diet-induced obesity. Communications biology, 5(1), p. 370. Springer Nature 10.1038/s42003-022-03305-z
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The obesity epidemic continues to worsen worldwide. However, the mechanisms initiating glucose dysregulation in obesity remain poorly understood. We assessed the role that colonic macrophage subpopulations play in glucose homeostasis in mice fed a high-fat diet (HFD). Concurrent with glucose intolerance, pro-inflammatory/monocyte-derived colonic macrophages increased in mice fed a HFD. A link between macrophage numbers and glycemia was established by pharmacological dose-dependent ablation of macrophages. In particular, colon-specific macrophage depletion by intrarectal clodronate liposomes improved glucose tolerance, insulin sensitivity, and insulin secretion capacity. Colonic macrophage activation upon HFD was characterized by an interferon response and a change in mitochondrial metabolism, which converged in mTOR as a common regulator. Colon-specific mTOR inhibition reduced pro-inflammatory macrophages and ameliorated insulin secretion capacity, similar to colon-specific macrophage depletion, but did not affect insulin sensitivity. Thus, pharmacological targeting of colonic macrophages could become a potential therapy in obesity to improve glycemic control.
Item Type: |
Journal Article (Original Article) |
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Division/Institute: |
04 Faculty of Medicine > Department of Gastro-intestinal, Liver and Lung Disorders (DMLL) > Clinic of Visceral Surgery and Medicine > Gastroenterology 04 Faculty of Medicine > Pre-clinic Human Medicine > BioMedical Research (DBMR) > DBMR Forschung Mu35 > Forschungsgruppe Gastroenterologie / Mukosale Immunologie 04 Faculty of Medicine > Pre-clinic Human Medicine > BioMedical Research (DBMR) > DBMR Forschung Mu35 > Forschungsgruppe Gastroenterologie / Mukosale Immunologie |
UniBE Contributor: |
Mooser, Catherine, Yilmaz, Bahtiyar (A), Fernandez Trigo, Nerea, Ganal-Vonarburg, Stephanie Christine |
Subjects: |
600 Technology > 610 Medicine & health |
ISSN: |
2399-3642 |
Publisher: |
Springer Nature |
Language: |
English |
Submitter: |
Pubmed Import |
Date Deposited: |
21 Apr 2022 15:21 |
Last Modified: |
05 Dec 2022 16:19 |
Publisher DOI: |
10.1038/s42003-022-03305-z |
PubMed ID: |
35440795 |
BORIS DOI: |
10.48350/169418 |
URI: |
https://boris.unibe.ch/id/eprint/169418 |
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