Figure 6. Blocking hypothalamic CCR5 with the antagonist-^MCCL5 induced glucose metabolism impairment and insulin resistance peripherally.

(a) Wildtype mice received 3^rd ventricle ICV infusion with aCSF as control or a CCL5 antagonist–Met-CCL5 (^MCCL5) to block CCR5 over two weeks. The body weight (b), daily food intake (c) and fasting blood glucose (d) in two groups of mice were similar. (e–h) The activation of insulin signaling manifested as phospho-Akt^S473 was reduced in ^MCCL5-treated mouse hypothalamus; the inhibitory signals as phosphor-IRS-1^S302 and phosphor-S6K^T421 were increased in mice receiving the antagonist-^MCCL5. OGTT (oral glucose tolerance test) (i), the AUC (area under curve) of OGTT (j), and ITT (insulin tolerance test) (k) were impaired in mice treated with antagonist ^MCCL5. (n = 5~6 in each groups, ***p = 0.001, **p = 0.0015, by Two-way ANOVA in i, k).