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. 2021 Sep 22;6(18):e145306. doi: 10.1172/jci.insight.145306

Figure 6. Celastrol-induced restoration of leptin sensitivity in POMC neurons from DIO mice requires PERK.

Figure 6

(A) A leptin-induced (100 nM) depolarization of LepR-expressing POMC neurons from mice fed a chow diet for 8 weeks. (B) Representative leptin-induced (100 nM) depolarization of LepR-expressing POMC neurons from mice fed a HFD for 8 weeks. (C) An example of leptin-induced (100 nM) depolarization of LepR-expressing POMC neurons from mice fed a HFD for 8 weeks and treated with celastrol (i.p., 100 μg/kg, Q.D.) for 2 days. (D) A leptin-induced (100 nM) depolarization of LepR-expressing POMC neurons from mice fed a HFD for 10 months. (E) A leptin-induced (100 nM) depolarization of POMC neurons from POMC-cre:PERKloxp/loxp:tdtomato mice fed a HFD for 10 months. (F) Representative leptin-induced (100 nM) depolarization of POMC neurons from POMC-cre:PERKloxp/loxp:tdtomato mice fed a HFD for 10 months and treated with celastrol (i.p., 100 μg/kg, Q.D.) for 2 days. (G and H) Histograms summarizing the effect of leptin (100 nM) on the membrane potential of POMC neurons from chow-fed and HFD-fed (8 weeks or 10 months) mice, with/without celastrol treatment. (G) The black bar shows the effects of leptin on POMC neurons from mice fed chow for 8 weeks (n = 8). The red bar shows the effects of leptin on POMC neurons from mice fed a HFD for 8 weeks (n = 8). The green bar shows the effects of leptin on POMC neurons from mice fed a HFD for 8 weeks, which were also injected with celastrol (100 μg/kg for 2 days, Q.D., n = 5). (H) The black bar shows the effects of leptin on POMC neurons from mice fed a HFD for 10 months (n = 6). The red bar shows the effects of leptin on POMC neurons from POMC-cre:PERKloxp/loxp:tdtomato mice fed a HFD for 10 months (n = 7). The green bar shows the effects of leptin on POMC neurons from POMC-cre:PERKloxp/loxp:tdtomato mice fed a HFD for 10 months, which also received an injection of celastrol (i.p., 100 μg/kg for 2 days, n = 8). Data are expressed as mean ± SEM. Two-way ANOVA with Tukey’s post hoc analyses, *P < 0.05.