Shh signaling blockade suppressed Dio3 induction and ameliorated low T3 state and glucose intolerance in vivo. (a) A brief time-course schematic diagram of cyclopamine administration and CLP modelling. (b) Representative immunoblots of Dio3 and SMO in skeletal muscles in the same settings as in (a; n = 6), with quantification presented. (c) Representative images of Dio3 IHC staining in the same setting as in (a) and its quantification (n = 6, scale bar: 50 μm). (d) Quantitative RT-PCR analysis of T3-responsive genes in samples in the same setting as in (a). (e) Serum T4, T3, and rT3 levels in rats subjected to sham or CLP modelling or CLP and cyclopamine administration (n = 6–8) detected by RIA. (f) Intraperitoneal glucose tolerance test of rats treated with sham CLP, or CLP + Cyclopamine (n = 6). (g) Proportion of TA or soleus muscles to body weight (n = 6). (h) Representative images of the HE staining of skeletal muscles in the same setting as in (a, n = 6) and quantitative analysis of fiber diameters by ImageJ. ^*P < 0.05. One-way ANOVA followed by Tukey’s multiple comparisons tests for (b, h) or one-way ANOVA followed by Tukey’s multiple comparisons tests for (c, d, e, f, and g). Quantitative data are represented as mean ± SD. NS not significant, Dio3 type 3 deiodinase, CLP cecal ligation and puncture, SMO protein smoothened, THR thyroid hormone receptor, T3 triiodothyronine, T4 thyroxine, rT3 reverse, T3, Cyclo cyclopamine, TA tibialis anterior, SOL soleus muscle