CCL5/RANTES contributes to hypothalamic insulin signaling for systemic insulin responsiveness through CCR5

Szu Yi Chou, Reni Ajoy, Chun Austin Changou, Ya Ting Hsieh, Yang Kao Wang, Barry Hoffer

研究成果: Article

10 引文 (Scopus)

摘要

Many neurodegenerative diseases are accompanied by metabolic disorders. CCL5/RANTES, and its receptor CCR5 are known to contribute to neuronal function as well as to metabolic disorders such as type 2 diabetes mellitus, obesity, atherosclerosis and metabolic changes after HIV infection. Herein, we found that the lack of CCR5 or CCL5 in mice impaired regulation of energy metabolism in hypothalamus. Immunostaining and co-immunoprecipitation revealed the specific expression of CCR5, associated with insulin receptors, in the hypothalamic arcuate nucleus (ARC). Both ex vivo stimulation and in vitro tissue culture studies demonstrated that the activation of insulin, and PI3K-Akt pathways were impaired in CCR5 and CCL5 deficient hypothalamus. The inhibitory phosphorylation of insulin response substrate-1 at Ser302 (IRS-1S302) but not IRS-2, by insulin was markedly increased in CCR5 and CCL5 deficient animals. Elevating CCR5/CCL5 activity induced GLUT4 membrane translocation and reduced phospho-IRS-1S302 through AMPKα-S6 Kinase. Blocking CCR5 using the antagonist, MetCCL5, abolished the de-phosphorylation of IRS-1S302 and insulin signal activation. In addition, intracerebroventricular delivery of Met CCL5 interrupted hypothalamic insulin signaling and elicited peripheral insulin responsiveness and glucose intolerance. Taken together, our data suggest that CCR5 regulates insulin signaling in hypothalamus which contributes to systemic insulin sensitivity and glucose metabolism.

原文English
文章編號37659
期刊Scientific reports
6
DOIs
出版狀態Published - 2016 十一月 29

指紋

Chemokine CCL5
Insulin
Hypothalamus
Phosphorylation
CCR5 Receptors
Ribosomal Protein S6 Kinases
Arcuate Nucleus of Hypothalamus
Glucose Intolerance
Insulin Receptor
Phosphatidylinositol 3-Kinases
Immunoprecipitation
Neurodegenerative Diseases
Type 2 Diabetes Mellitus
Energy Metabolism
HIV Infections
Insulin Resistance
Atherosclerosis
Obesity
Glucose
Membranes

All Science Journal Classification (ASJC) codes

  • General

引用此文

Chou, Szu Yi ; Ajoy, Reni ; Changou, Chun Austin ; Hsieh, Ya Ting ; Wang, Yang Kao ; Hoffer, Barry. / CCL5/RANTES contributes to hypothalamic insulin signaling for systemic insulin responsiveness through CCR5. 於: Scientific reports. 2016 ; 卷 6.
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CCL5/RANTES contributes to hypothalamic insulin signaling for systemic insulin responsiveness through CCR5. / Chou, Szu Yi; Ajoy, Reni; Changou, Chun Austin; Hsieh, Ya Ting; Wang, Yang Kao; Hoffer, Barry.

於: Scientific reports, 卷 6, 37659, 29.11.2016.

研究成果: Article

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