Fig. 3. Transplantation of HUMBLE or brown control cells facilitates glucose metabolism and thermogenesis in mice.

(A) Schematic protocol for transplantation of white control, HUMBLE or brown control preadipocytes into nude mice fed with 45% HFD. (B-D) Body weight (BW) change (B), GTT (C), and ITT (D) over 4 weeks in mice transplanted with white control, HUMBLE or brown control cells; n = 7 mice per group. (E) Heat production of mice 4 weeks after transplantation with white control, HUMBLE or brown control cells. Mean heat production over a 14-hour dark/light cycle (shown as the black/white bar above the left chart) was calculated (right); n = 7 mice per group. (F) Core body temperature of mice 4 weeks after transplantation with white control, HUMBLE, or brown control cells that were challenged at 5°C for 6 hours; n = 7 mice per group. (G) Human white preadipocytes from a second human subject (A38) were transfected with the CRISPR-SAM system and either empty vector (EV) or sgRNA-A and UCP1 mRNA expression determined. (H and I) UCP1 mRNA expression (H) and thermogenesis (I) in differentiated adipocytes from human A38 white preadipocytes transfected with EV (A38_white control) or sgRNA-A (A38_HUMBLE) and human brown A38 preadipocytes (A38_brown control). (J to L), BW change (J), GTT (K) and ITT (L) in mice over 4 weeks after transplantation with A38_white control, A38_HUMBLE or A38_brown control preadipocytes; n = 4 mice per group. In all charts, data are presented as means ± s.e.m.; *p < 0.05; **p < 0.01; ***p < 0.001.