Targeting colonic macrophages improves glycemic control in high-fat diet-induced obesity.
Journal
Communications biology
ISSN: 2399-3642
Titre abrégé: Commun Biol
Pays: England
ID NLM: 101719179
Informations de publication
Date de publication:
19 04 2022
19 04 2022
Historique:
received:
21
10
2021
accepted:
22
03
2022
entrez:
20
4
2022
pubmed:
21
4
2022
medline:
22
4
2022
Statut:
epublish
Résumé
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.
Identifiants
pubmed: 35440795
doi: 10.1038/s42003-022-03305-z
pii: 10.1038/s42003-022-03305-z
pmc: PMC9018739
doi:
Substances chimiques
Blood Glucose
0
TOR Serine-Threonine Kinases
EC 2.7.11.1
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
370Informations de copyright
© 2022. The Author(s).
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