| RRC ID |
72150
|
| 著者 |
Kawamura N, Katsuura G, Yamada-Goto N, Nakama R, Kambe Y, Miyata A, Furuyashiki T, Narumiya S, Ogawa Y, Inui A.
|
| タイトル |
Brain fractalkine-CX3CR1 signalling is anti-obesity system as anorexigenic and anti-inflammatory actions in diet-induced obese mice.
|
| ジャーナル |
Sci Rep
|
| Abstract |
Fractalkine is one of the CX3C chemokine family, and it is widely expressed in the brain including the hypothalamus. In the brain, fractalkine is expressed in neurons and binds to a CX3C chemokine receptor 1 (CX3CR1) in microglia. The hypothalamus regulates energy homeostasis of which dysregulation is associated with obesity. Therefore, we examined whether fractalkine-CX3CR1 signalling involved in regulating food intake and hypothalamic inflammation associated with obesity pathogenesis. In the present study, fractalkine significantly reduced food intake induced by several experimental stimuli and significantly increased brain-derived neurotrophic factor (BDNF) mRNA expression in the hypothalamus. Moreover, tyrosine receptor kinase B (TrkB) antagonist impaired fractalkine-induced anorexigenic actions. In addition, compared with wild-type mice, CX3CR1-deficient mice showed a significant increase in food intake and a significant decrease in BDNF mRNA expression in the hypothalamus. Mice fed a high-fat diet (HFD) for 16 weeks showed hypothalamic inflammation and reduced fractalkine mRNA expression in the hypothalamus. Intracerebroventricular administration of fractalkine significantly suppressed HFD-induced hypothalamic inflammation in mice. HFD intake for 4 weeks caused hypothalamic inflammation in CX3CR1-deficient mice, but not in wild-type mice. These findings suggest that fractalkine-CX3CR1 signalling induces anorexigenic actions via activation of the BDNF-TrkB pathway and suppresses HFD-induced hypothalamic inflammation in mice.
|
| 巻・号 |
12(1)
|
| ページ |
12604
|
| 公開日 |
2022-7-23
|
| DOI |
10.1038/s41598-022-16944-3
|
| PII |
10.1038/s41598-022-16944-3
|
| PMID |
35871167
|
| PMC |
PMC9308795
|
| MeSH |
Animals
Anti-Inflammatory Agents
Brain / metabolism
Brain-Derived Neurotrophic Factor* / genetics
Brain-Derived Neurotrophic Factor* / metabolism
CX3C Chemokine Receptor 1 / genetics
CX3C Chemokine Receptor 1 / metabolism
Chemokine CX3CL1* / genetics
Chemokine CX3CL1* / metabolism
Diet, High-Fat / adverse effects
Inflammation / metabolism
Mice
Mice, Inbred C57BL
Mice, Obese
Obesity / etiology
Obesity / metabolism
RNA, Messenger
|
| IF |
3.998
|
| リソース情報 |
| ヒト・動物細胞 |
MG6(RCB2403) |
