FIG. 7.
Macrophage depletion using clodronate-liposomes does not affect short-term HFD-dependent adipocyte insulin resistance. Mice were treated with NCD or 60% HFD in the presence or absence of clodronate injection. Mice were given clodronate injection (100 mg/kg i.p.) 3 days before HFD, which was followed by a second and third injection every 3 days (at days 0 and 3). A: Flow cytometry analysis of CD11c+ macrophages in adipose tissue. V, vehicle (empty liposomes); C, clodronate-liposomes. B: Whole-mount immunohistochemistry analysis of epididymal adipose tissue. Veh, vehicle; Clod, clodronate-liposomes. C: Cytokine concentration in the mouse sera injected with vehicle and clodronate. W, week. *P < 0.05. D: Glucose-uptake assays using primary adipocytes from mice treated with NCD or HFD for 1 week with or without clodronate injection. White columns denote relative glucose uptake activity without insulin. Black columns denote relative glucose uptake activity with insulin. Cld, clodronate-liposomes. E: Oral glucose tolerance test (OGTT) of mice treated with HFD for 3 days. #P < 0.05 Veh-NCD vs. Veh-HFD; *P < 0.05 Cld-NCD vs. Cld-HFD; **P < 0.01 Cld-NCD vs. Cld-HFD; ***P < 0.001 Cld-NCD vs. Cld-HFD. n = 6. F: Glucose tolerance test of mice treated with HFD for 7 days. #P < 0.05 Veh-NCD vs. Veh-HFD; ##P < 0.01 Veh-NCD vs. Veh-HFD; ###P < 0.001 Veh-NCD vs. Veh-HFD; *P < 0.05 Cld-NCD vs. Cld-HFD; **P < 0.01 Cld-NCD vs. Cld-HFD. n = 6. G: Homeostasis model assessment of insulin resistance (HOMA-IR). H–J: Hematopoietic cell-specific JNK deficiency does not affect short-term HFD-induced insulin resistance. For the generation of radiation chimera, C57BL/6J mice received a lethal dose of 10 Gy of ionizing radiation, followed by tail vein injection of 107 bone marrow cells either from wild-type (WT) or JNK KO mice. After 6 weeks of bone marrow reconstitution, mice were subjected to 3 or 7 days of HFD, followed by hyperinsulinemic-euglycemic clamp. n = 4 to 5. H: GIR. I: ISGDR. J: Insulin-dependent hepatic glucose suppression. BMT, bone marrow transplantation. (A high-quality digital representation of this figure is available in the online issue.)