2. Academic Validation
  3. Targeting colonic macrophages improves glycemic control in high-fat diet-induced obesity

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

  • Commun Biol. 2022 Apr 19;5(1):370. doi: 10.1038/s42003-022-03305-z.
Theresa V Rohm 1 2,  Lena Keller 1 2,  Angela J T Bosch 1 2,  Shefaa AlAsfoor 1 2,  Zora Baumann 1 2,  Amandine Thomas 3,  Sophia J Wiedemann 1 2,  Laura Steiger 1 2,  Elise Dalmas 1 2,  Josua Wehner 1 2,  Leila Rachid 1 2,  Catherine Mooser 4 5,  Bahtiyar Yilmaz 4 5,  Nerea Fernandez Trigo 4 5,  Annaise J Jauch 2,  Stephan Wueest 6,  Daniel Konrad 6,  Sandrine Henri 7,  Jan H Niess 2 8,  Petr Hruz 2 8,  Stephanie C Ganal-Vonarburg 4 5,  Julien Roux 2 9,  Daniel T Meier 1 2,  Claudia Cavelti-Weder 10 11 12
Affiliations

Affiliations

  • 1 Clinic of Endocrinology, Diabetes and Metabolism, University Hospital Basel, Basel, Switzerland.
  • 2 Department of Biomedicine (DBM), University of Basel, University Hospital Basel, Basel, Switzerland.
  • 3 Biozentrum, University of Basel, Basel, Switzerland.
  • 4 Department of Visceral Surgery und Medicine, Bern University Hospital, University of Bern, Bern, Switzerland.
  • 5 Department for BioMedical Research (DBMR), University of Bern, Bern, Switzerland.
  • 6 Division of Pediatric Endocrinology and Diabetology, and Children's Research Center, University Children's Hospital, University of Zurich, Zurich, Switzerland.
  • 7 Centre d'Immunologie de Marseille-Luminy, Aix Marseille Université, INSERM, CNRS, Marseille, France.
  • 8 Clarunis, Department of Visceral Surgery, University Center for Gastrointestinal and Liver Diseases, St. Clara Hospital and University Hospital Basel, Basel, Switzerland.
  • 9 Swiss Institute of Bioinformatics (SIB), Basel, Switzerland.
  • 10 Clinic of Endocrinology, Diabetes and Metabolism, University Hospital Basel, Basel, Switzerland. [email protected].
  • 11 Department of Biomedicine (DBM), University of Basel, University Hospital Basel, Basel, Switzerland. [email protected].
  • 12 Department of Endocrinology, Diabetology and Clinical Nutrition, University Hospital Zurich (USZ) and University of Zurich (UZH), Zurich, Switzerland. [email protected].
PMID: 35440795 DOI: 10.1038/s42003-022-03305-z
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.

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