Display options
Cite
Heiss CN, Mannerås-Holm L, Lee YS, et al. The gut microbiota regulates hypothalamic inflammation and leptin sensitivity in Western diet-fed mice via a GLP-1R-dependent mechanism. Cell Rep. 2021;35(8):109163doi: 10.1016/j.celrep.2021.109163.
Heiss, C. N., Mannerås-Holm, L., Lee, Y. S., Serrano-Lobo, J., Håkansson Gladh, A., Seeley, R. J., Drucker, D. J., Bäckhed, F., & Olofsson, L. E. (2021). The gut microbiota regulates hypothalamic inflammation and leptin sensitivity in Western diet-fed mice via a GLP-1R-dependent mechanism. Cell reports, 35(8), 109163. https://doi.org/10.1016/j.celrep.2021.109163
Heiss, Christina N, et al. "The gut microbiota regulates hypothalamic inflammation and leptin sensitivity in Western diet-fed mice via a GLP-1R-dependent mechanism." Cell reports vol. 35,8 (2021): 109163. doi: https://doi.org/10.1016/j.celrep.2021.109163
Heiss CN, Mannerås-Holm L, Lee YS, Serrano-Lobo J, Håkansson Gladh A, Seeley RJ, Drucker DJ, Bäckhed F, Olofsson LE. The gut microbiota regulates hypothalamic inflammation and leptin sensitivity in Western diet-fed mice via a GLP-1R-dependent mechanism. Cell Rep. 2021 May 25;35(8):109163. doi: 10.1016/j.celrep.2021.109163. PMID: 34038733.
Copy Download .nbib Format: NLM
Share it on

Cell Rep. 2021 May 25;35(8):109163. doi: 10.1016/j.celrep.2021.109163.

The gut microbiota regulates hypothalamic inflammation and leptin sensitivity in Western diet-fed mice via a GLP-1R-dependent mechanism.

Cell reports

Christina N Heiss, Louise Mannerås-Holm, Ying Shiuan Lee, Julia Serrano-Lobo, Anna Håkansson Gladh, Randy J Seeley, Daniel J Drucker, Fredrik Bäckhed, Louise E Olofsson

Affiliations

  1. Wallenberg Laboratory, Department of Molecular and Clinical Medicine, Institute of Medicine, University of Gothenburg, 41345 Gothenburg, Sweden.
  2. Department of Surgery, University of Michigan Medical School, Ann Arbor, MI 48109, USA.
  3. Department of Medicine, Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, University of Toronto, ON M5G 1X5, Canada.
  4. Wallenberg Laboratory, Department of Molecular and Clinical Medicine, Institute of Medicine, University of Gothenburg, 41345 Gothenburg, Sweden; Novo Nordisk Foundation Center for Basic Metabolic Research, Section for Metabolic Receptology and Enteroendocrinology, Faculty of Health Sciences, University of Copenhagen, 2200 Copenhagen, Denmark; Department of Clinical Physiology, Region Västra Götaland, Sahlgrenska University Hospital, 41345 Gothenburg, Sweden.
  5. Wallenberg Laboratory, Department of Molecular and Clinical Medicine, Institute of Medicine, University of Gothenburg, 41345 Gothenburg, Sweden. Electronic address: [email protected].

PMID: 34038733 DOI: 10.1016/j.celrep.2021.109163

Abstract

Mice lacking a microbiota are protected from diet-induced obesity. Previous studies have shown that feeding a Western diet causes hypothalamic inflammation, which in turn can lead to leptin resistance and weight gain. Here, we show that wild-type (WT) mice with depleted gut microbiota, i.e., germ-free (GF) and antibiotic-treated mice, have elevated levels of glucagon-like peptide-1 (GLP-1), are protected against diet-induced hypothalamic inflammation, and have enhanced leptin sensitivity when fed a Western diet. Using GLP-1 receptor (GLP-1R)-deficient mice and pharmacological inhibition of the GLP-1R in WT mice, we demonstrate that intact GLP-1R signaling is required for preventing hypothalamic inflammation and enhancing leptin sensitivity. Furthermore, we show that astrocytes express the GLP-1R, and deletion of the receptor in glial fibrillary acidic protein (GFAP)-expressing cells diminished the antibiotic-induced protection against diet-induced hypothalamic inflammation. Collectively, our results suggest that depletion of the gut microbiota attenuates diet-induced hypothalamic inflammation and enhances leptin sensitivity via GLP-1R-dependent mechanisms.

Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.

Keywords: GLP-1; astrocytes; diet-induced obesity; glucagon-like peptide-1; gut microbiota; hypothalamic inflammation; leptin sensitivity; microglia

Conflict of interest statement

Declaration of interests D.J.D. has served as an advisor or consultant or speaker within the past 12 months to Forkhead Biotherapeutics, Intarcia Therapeutics, Kallyope, Eli Lilly, Merck Research Labo

Publication Types