Exogenous T4 administration restores the actions of UA in PTU-treated mice.

(A) Schematic diagram of mice treatment. UA-treated and control mice were initially treated with PTU (8.5 mg/100 ml in the drinking water) for 2 weeks and subsequently received PTU plus T4 (1 μg/100 g in 0.2% BSA-PBS) for a period of 4 weeks. (B) Body weight time course. (C) Daily food intake. Weight of (D) total fat mass, (E) BAT, and (F) iWAT (n = 6). (G) Levels of plasma glucose. (H) Body temperature of mice placed at 21°(C). mRNA expression of thermogenic genes in (I) BAT and (J) iWAT. Immunoblot of UCP-1 and PGC-1α protein in (K) BAT and (L) iWAT (n = 3). (M) Schematic diagram of actions of UA in the regulation of thermogenesis through TH. The underlying data for this figure can be found in S1 Data. Accβ, Acetyl-CoA carboxylase beta; BAT, brown adipose tissue; BSA, bovine serum albumin; Cidea, Cell death inducing DFFA like effector A; Cox7a, Cytochrome c oxidase subunit 7a1; Dio2, Deiodinase 2; HFD, high-fat diet; iWAT, inguinal white adipose tissue; Ldhβ, Lactate dehydrogenase B; Pgc1-α, Peroxisome proliferator-activated receptor gamma coactivator 1α; PTU, propylthiouracil; TRβ, TH Receptor β; T3, triiodothyronine; T4, tetraiodothyronine; UA, urolithin A; UCP-1, Uncoupling protein 1.