Figure 3.

OATPs but not NTCP transport T4. (A) Dio2 messenger RNA (mRNA) expression levels in BAT of male HFD-fed Oatp1a/1b KO mice treated daily with placebo or Myrcludex B for 3.5 weeks (n = 9–10). Reverse transcription quantitative polymerase chain reaction samples are relative to the geometric mean of control genes 36b4 and Hprt and normalized to reference values of male WT HFD-fed placebo treated mice. (B) Plasma T3 and (C) plasma T4 levels of the mice described in panel A. (D) Dio1 mRNA expression levels in the liver, reverse transcription quantitative polymerase chain reaction samples are relative to the geometric mean of control genes 36b4 and tbp and normalized to reference values of male WT HFD-fed placebo treated mice. (E) T4 signal in plasma and (F) half-life of the T4 plasma clearance in WT, Oatp1a/1b KO, or Oatp1a/1b KO reconstituted with human OATP1B1 or OATP1B3 (Oatp1a/1b KO-h1B1 or Oatp1a/1b KO-h1B3) after Myrcludex B or placebo administration (n = 13–14, equal male and female animals). [¹²⁵I]T4 was administered intravenously via the tail vein at t=0 and ¹²⁵I activity (cpm) was measured. Appearance of radiolabeled T4 in (G) bile and (H) the liver. Data are expressed as percentage of input. (I) Plasma T3 and (J) plasma T4 levels of female HFD-fed WT and Oatp1a/1b KO-h1B1 mice treated daily with placebo or Myrcludex B for 3.5 weeks (n = 9–10). Error bars show SEM, asterisk indicates significant changes to the placebo treated control group, hashtag indicates significant changes to the placebo treated Oatp1a/1b KO(-h1B1) group.