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

Research output: Contribution to journal › Journal article › Research › peer-review

Standard

The gut microbiota regulates hypothalamic inflammation and leptin sensitivity in Western diet-fed mice via a GLP-1R-dependent mechanism. / Heiss, Christina N.; Mannerås-Holm, Louise; Lee, Ying Shiuan; Serrano-Lobo, Julia; Håkansson Gladh, Anna; Seeley, Randy J.; Drucker, Daniel J.; Bäckhed, Fredrik; Olofsson, Louise E.

In: Cell Reports, Vol. 35, No. 8, 109163, 2021.

Research output: Contribution to journal › Journal article › Research › peer-review

Harvard

Heiss, CN, Mannerås-Holm, L, Lee, YS, Serrano-Lobo, J, Håkansson Gladh, A, Seeley, RJ, Drucker, DJ, Bäckhed, F & Olofsson, LE 2021, 'The gut microbiota regulates hypothalamic inflammation and leptin sensitivity in Western diet-fed mice via a GLP-1R-dependent mechanism', Cell Reports, vol. 35, no. 8, 109163. https://doi.org/10.1016/j.celrep.2021.109163

APA

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

Vancouver

Heiss CN, Mannerås-Holm L, Lee YS, Serrano-Lobo J, Håkansson Gladh A, Seeley RJ et al. The gut microbiota regulates hypothalamic inflammation and leptin sensitivity in Western diet-fed mice via a GLP-1R-dependent mechanism. Cell Reports. 2021;35(8). 109163. https://doi.org/10.1016/j.celrep.2021.109163

Author

Heiss, Christina N. ; Mannerås-Holm, Louise ; Lee, Ying Shiuan ; Serrano-Lobo, Julia ; Håkansson Gladh, Anna ; Seeley, Randy J. ; Drucker, Daniel J. ; Bäckhed, Fredrik ; Olofsson, Louise E. / The gut microbiota regulates hypothalamic inflammation and leptin sensitivity in Western diet-fed mice via a GLP-1R-dependent mechanism. In: Cell Reports. 2021 ; Vol. 35, No. 8.

Bibtex

@article{4a8068d08ae04c5aa9ac086381885665,
title = "The gut microbiota regulates hypothalamic inflammation and leptin sensitivity in Western diet-fed mice via a GLP-1R-dependent mechanism",
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.",
keywords = "astrocytes, diet-induced obesity, GLP-1, glucagon-like peptide-1, gut microbiota, hypothalamic inflammation, leptin sensitivity, microglia",
author = "Heiss, {Christina N.} and Louise Manner{\aa}s-Holm and Lee, {Ying Shiuan} and Julia Serrano-Lobo and {H{\aa}kansson Gladh}, Anna and Seeley, {Randy J.} and Drucker, {Daniel J.} and Fredrik B{\"a}ckhed and Olofsson, {Louise E.}",
note = "Publisher Copyright: {\textcopyright} 2021 The Authors",
year = "2021",
doi = "10.1016/j.celrep.2021.109163",
language = "English",
volume = "35",
journal = "Cell Reports",
issn = "2211-1247",
publisher = "Cell Press",
number = "8",

}

RIS

TY - JOUR

T1 - The gut microbiota regulates hypothalamic inflammation and leptin sensitivity in Western diet-fed mice via a GLP-1R-dependent mechanism

AU - Heiss, Christina N.

AU - Mannerås-Holm, Louise

AU - Lee, Ying Shiuan

AU - Serrano-Lobo, Julia

AU - Håkansson Gladh, Anna

AU - Seeley, Randy J.

AU - Drucker, Daniel J.

AU - Bäckhed, Fredrik

AU - Olofsson, Louise E.

N1 - Publisher Copyright: © 2021 The Authors

PY - 2021

Y1 - 2021

N2 - 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.

AB - 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.

KW - astrocytes

KW - diet-induced obesity

KW - GLP-1

KW - glucagon-like peptide-1

KW - gut microbiota

KW - hypothalamic inflammation

KW - leptin sensitivity

KW - microglia

U2 - 10.1016/j.celrep.2021.109163

DO - 10.1016/j.celrep.2021.109163

M3 - Journal article

C2 - 34038733

AN - SCOPUS:85106476645

VL - 35

JO - Cell Reports

JF - Cell Reports

SN - 2211-1247

IS - 8

M1 - 109163

ER -

ID: 272422158