The gut microbiota regulates hypothalamic inflammation and leptin sensitivity in Western diet-fed mice via a GLP-1R-dependent mechanism
| Autor: | Christina N. Heiss, Randy J. Seeley, Ying Shiuan Lee, Fredrik Bäckhed, Anna Håkansson Gladh, Daniel J. Drucker, Louise Mannerås-Holm, Julia Serrano-Lobo, Louise E. Olofsson |
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| Rok vydání: | 2021 |
| Předmět: |
Leptin
Male 0301 basic medicine endocrine system medicine.medical_specialty diet-induced obesity Hypothalamus microglia Gut flora Glucagon-Like Peptide-1 Receptor General Biochemistry Genetics and Molecular Biology leptin sensitivity Mice 03 medical and health sciences 0302 clinical medicine Internal medicine medicine Animals Humans Obesity Receptor hypothalamic inflammation Inflammation gut microbiota Glial fibrillary acidic protein biology Microglia digestive oral and skin physiology astrocytes biology.organism_classification medicine.disease Glucagon-like peptide-1 Gastrointestinal Microbiome 030104 developmental biology medicine.anatomical_structure Endocrinology glucagon-like peptide-1 Diet Western biology.protein medicine.symptom GLP-1 Weight gain hormones hormone substitutes and hormone antagonists 030217 neurology & neurosurgery |
| Zdroj: | 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, vol. 35, no. 8, 109163 . https://doi.org/10.1016/j.celrep.2021.109163 |
| ISSN: | 2211-1247 |
| DOI: | 10.1016/j.celrep.2021.109163 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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