Reference - Detail
| RRC ID | 84274 |
|---|---|
| Author | Fu Y, Kaneko K, Lin HY, Mo Q, Xu Y, Suganami T, Ravn P, Fukuda M. |
| Title | Gut Hormone GIP Induces Inflammation and Insulin Resistance in the Hypothalamus. |
| Journal | Endocrinology |
| Abstract |
The hypothalamus plays a critical role in controlling energy balance. High-fat diet (HFD) feeding increases the gene expression of proinflammatory mediators and decreases insulin actions in the hypothalamus. Here, we show that a gut-derived hormone, glucose-dependent insulinotropic polypeptide (GIP), whose levels are elevated during diet-induced obesity, promotes and mediates hypothalamic inflammation and insulin resistance during HFD-induced obesity. Unbiased ribonucleic acid sequencing of GIP-stimulated hypothalami revealed that hypothalamic pathways most affected by intracerebroventricular (ICV) GIP stimulation were related to inflammatory-related responses. Subsequent analysis demonstrated that GIP administered either peripherally or centrally, increased proinflammatory-related factors such as Il-6 and Socs3 in the hypothalamus, but not in the cortex of C57BL/6J male mice. Consistently, hypothalamic activation of IκB kinase-β inflammatory signaling was induced by ICV GIP. Further, hypothalamic levels of proinflammatory cytokines and Socs3 were significantly reduced by an antagonistic GIP receptor (GIPR) antibody and by GIPR deficiency. Additionally, centrally administered GIP reduced anorectic actions of insulin in the brain and diminished insulin-induced phosphorylation of Protein kinase B and Glycogen synthase kinase 3β in the hypothalamus. Collectively, these findings reveal a previously unrecognized role for brain GIP signaling in diet-induced inflammation and insulin resistance in the hypothalamus. |
| Volume | 161(9) |
| Published | 2020-9-1 |
| DOI | 10.1210/endocr/bqaa102 |
| PII | 5865317 |
| PMID | 32603429 |
| PMC | PMC7410368 |
| MeSH | Animals Diet, High-Fat Encephalitis / chemically induced* Encephalitis / genetics Gastric Inhibitory Polypeptide / administration & dosage Gastric Inhibitory Polypeptide / pharmacology* Gastric Inhibitory Polypeptide / physiology Hypothalamus / drug effects* Hypothalamus / immunology Hypothalamus / pathology Inflammation / chemically induced* Inflammation / genetics Infusions, Intraventricular Insulin Resistance* / genetics Male Mice Mice, Inbred C57BL Mice, Knockout Mice, Obese Receptors, Gastrointestinal Hormone / genetics Receptors, Gastrointestinal Hormone / physiology* Signal Transduction / drug effects Signal Transduction / genetics Up-Regulation / drug effects Up-Regulation / genetics |
| IF | 3.934 |
| Altmetric score |
オルトメトリクス指標項目
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| The most frequently cited source | X(Twitter) |
| Total number of mentions | 33 |
| Altmetric score changes over past 6months | 0.0 |
| Resource | |
| Mice | RBRC00782 |