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. Author manuscript; available in PMC: 2018 Aug 5.
Published in final edited form as: Nat Med. 2018 Feb 5;24(3):292–303. doi: 10.1038/nm.4481

Figure 6.

Figure 6

Enhancing proteostasis in BAT alleviates insulin resistance in DIO and ob/ob mice. (a) Strategy for contralateral intraBAT injection of adenovirus carrying LacZ (AV-LacZ) and Nrf1 (AV-Nrf1) into WT and Nfe2l1ΔBAT mice at 22 °C. (b) mRNA levels of Nfe2l1 and proteasome subunits in BAT of Nfe2l1ΔBAT mice BAT-injected with AV-LacZ and AV-Nrf1 (Biol. replicates n = 6, normalized to 18s, *P < 0.05 by Student’s t-Test). (c) Proteasome activity in WT and Nfe2l1ΔBAT mice BAT-injected with AV-LacZ and AV-Nrf1 (Biol. replicates n = 4 for WT and n = 6 for Nfe2l1ΔBAT, *P < 0.05 by 2-way ANOVA). (d) Photograph of iBAT of a Nfe2l1ΔBAT mouse injected with AV-LacZ (left) and AV-Nrf1 (right) contralaterally (Scale bar, 5 mm). (e) Representative H&E histology and (f) Ucp1 IHC of Nfe2l1ΔBAT mice injected with AV-LacZ and AV-Nrf1 (Biol. replicates n = 3; Scale bars, 100 μm). (g) BAT uptake of radiolabelled tracers after a combined oral fat and glucose tolerance test in WT and Nfe2l1ΔBAT mice injected with AV-LacZ and AV-Nrf1 (Biol. replicates n = 6 for WT and n = 10 for Nfe2l1ΔBAT, *P < 0.05 by 2-way ANOVA. (h) Strategy for intraBAT injection of AV-LacZ or AV-Nrf1 into diet-induced obese (DIO) mice. (i) mRNA levels of Nfe2l1 in BAT of DIO mice BAT-injected with AV-LacZ or AV-Nrf1 (Biol. replicates n = 6, normalized to Tbp, *P < 0.05 by Student’s t-Test). (j) Proteasome activity in DIO mice BAT-injected with AV-LacZ or AV-Nrf1 (biol. replicates n = 6, *P < 0.05 by Student’s t-Test). (k) Insulin tolerance test in DIO mice BAT-injected with AV-LacZ or AV-Nrf1 (Biol. replicates n = 10, *P < 0.05 by Student’s t-Test on AUC). (l) Strategy for intraBAT injection of AV-LacZ or AV-PA28α into diet-induced obese (DIO) mice. (m) mRNA levels of PA28α (encoded by Psme1) in BAT of DIO mice BAT-injected with AV-LacZ or AV-PA28α (Biol. replicates n = 6 for AV-LacZ and n = 7 for AV-PA28α, normalized to Tbp, *P < 0.05 by Student’s t-Test). (n) Proteasome activity in DIO mice BAT-injected with AV-LacZ or AV-PA28α (Biol. replicates n = 6 for AV-LacZ and n = 7 for AV-PA28α, *P < 0.05 by Student’s t-Test). (o) Insulin tolerance test in DIO mice BAT-injected with AV-LacZ or AV-PA28α (Biol. replicates n = 5, *P < 0.05 by Student’s t-Test on AUC). (p) Strategy for intraBAT injection of AV-LacZ or AV-PA28α into ob/ob mice. (q) mRNA levels of PA28α (encoded by Psme1) in BAT of ob/ob mice BAT-injected with AV-LacZ or AV-PA28α (Biol. replicates n = 10 for AV-LacZ and n = 8 for AV-PA28α, normalized to Tbp, *P < 0.05 by Student’s t-Test). (r) Proteasome activity in ob/ob mice BAT-injected with AV-LacZ or AV-PA28α (Biol. replicates n = 10 for AV-LacZ and n = 8 for AV-PA28α, *P < 0.05 by Student’s t-Test). (s) Insulin tolerance test in DIO mice BAT-injected with AV-LacZ or AV-PA28α (Biol. replicates n = 10 for AV-LacZ and n = 8 for AV-PA28α, *P < 0.05 by Student’s t-Test on AUC).