The Involvement of Neuronal CCR5-mediated Signaling in the Regulation of Energy Homeostasis

• Main Authors: Yin-Chien Chen, 陳尹蒨
• Other Authors: Po-Shiuan Hsieh
• Format: Others
• Language: zh-TW
• Published: 2013
• Online Access: http://ndltd.ncl.edu.tw/handle/91753752984477286950

碩士 === 國防醫學院 === 生理學研究所 === 101 === Hypothalamus is the integration center for body energy homeostasis. CC Chemokine 5 (CCL5/RANTES) signal in central nerve system has been reported to increase rat body temperature and decrease food intake with a direct hypothalamic injection. CC chemokine receptor 5 (CCR5), belongs to one of CCL5 receptors, up-regulated in human obese adipose tissue has strong correlation with peripheral glucose utility. The role and contribution of CCL5/CCR5 signaling in hypothalamic remain unclear. The aim of this study is to investigate hypothalamic CCL5/CCR5 signaling in energy homeostasis and adaptive thermogenesis. In 13weeks-age normal chow diet group, after one week continuing cold exposure, body weight loss of CCR5-/- mice was significantly higher than that in C57BL/6 mice. Food consumption of CCR5-/- mice was lower than that in C57BL/6 mice. The blood glucose of C57BL/6 mice was elevated 32% in cold environment; which conversely was decreased 16% in CCR5-/- mice. Insulin receptor and its substrate protein - IRS1( Insulin receptor substrate 1) and mitochondria energy generating enzyme - UCP2 (Uncoupling protein 2) have decreased about 28% and 13% in C57BL/6 but increased 50% and 62% in CCR5-/- mice with qRT-PCR analysis.This results suggested that hypothalamic CCR5 might play a negative regulatory role in energy expenditure. In 20weeks-age normal chow diet group,the energy related gene expression was decreased on CCR5-/- mice under cold exposure,indicated that CCR5 gene maybe have different expression level under different age.