瘦素
肠道菌群
机制(生物学)
内分泌学
内科学
生物
炎症
肥胖
免疫学
医学
认识论
哲学
作者
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
出处
期刊:Cell Reports
[Elsevier]
日期:2021-05-01
卷期号:35 (8): 109163-109163
被引量:48
标识
DOI:10.1016/j.celrep.2021.109163
摘要
Summary
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.
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