Navigation auf zora.uzh.ch

Search ZORA

ZORA (Zurich Open Repository and Archive)

Targeting colonic macrophages improves glycemic control in high-fat diet-induced obesity

Abstract

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.

Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > University Hospital Zurich > Clinic for Endocrinology and Diabetology
04 Faculty of Medicine > University Children's Hospital Zurich > Medical Clinic
Dewey Decimal Classification:610 Medicine & health
Scopus Subject Areas:Health Sciences > Medicine (miscellaneous)
Life Sciences > General Biochemistry, Genetics and Molecular Biology
Life Sciences > General Agricultural and Biological Sciences
Language:English
Date:19 April 2022
Deposited On:16 May 2022 06:30
Last Modified:27 Jan 2025 02:38
Publisher:Nature Publishing Group
ISSN:2399-3642
OA Status:Gold
Free access at:PubMed ID. An embargo period may apply.
Publisher DOI:https://doi.org/10.1038/s42003-022-03305-z
PubMed ID:35440795
Download PDF  'Targeting colonic macrophages improves glycemic control in high-fat diet-induced obesity'.
Preview
  • Content: Published Version
  • Licence: Creative Commons: Attribution 4.0 International (CC BY 4.0)

Metadata Export

Statistics

Citations

Dimensions.ai Metrics
18 citations in Web of Science®
17 citations in Scopus®
Google Scholar™

Altmetrics

Downloads

11 downloads since deposited on 16 May 2022
3 downloads since 12 months
Detailed statistics

Authors, Affiliations, Collaborations

Similar Publications