a, Representative images of wild-type and K19CreER;Rosa-rtTA;TetO-Gli2ΔN mice after 5 months of HFD. Gli2ΔN mice were treated with tamoxifen at 7 weeks of age and with doxycycline for 1 week after each depilation. b, Whole-mount imaging of dorsal skin from control and Gli2ΔN mice (left) and quantification (right; n = 3, two-tailed unpaired t-test; mean ± s.d.). Arrows, follicles without HFSC-containing bulges. Scale bar, 60 μm. c, Representative images of HFD-fed mice treated with or without SAG, a hedgehog-activating reagent, for 1 week after each depilation (n = 7) (Extended Data Fig. 9j). Veh, vehicle. d, Schematic of our proposed mechanism of HFD-induced hair loss. Short-term HFD feeding induces an epidermal differentiation program by inducing accumulation of ROS via aerobic respiration, but retains the HFSC pool. Long-term HFD feeding additionally induces NFκB signalling and accumulation of abundant lipids, which causes HFSC depletion and eventual hair loss. Bg, bulge. DP, dermal papilla. FFA, free fatty acids.