(A) Initial working hypothesis: obesogenic diets increase nutrient, hormone, and growth factor availability, thereby activating mTORC1 and promoting TD with gland enlargement. (B–D) mTORC1 activity, assessed by phospho-S6/total S6 (pS6/tS6), in thyroid protein extracts from male C57BL/6 mice fed regular diet (RD) or HFD after 3 or 12 weeks (B), 18 weeks (C), and 20 weeks (D), with representative immunoblots. (E–J) Thyroid weight (E), thyroid weight/body weight ratio (F), thyroxine (T4) (G), thyrotropin (TSH) (H), thyroidal gene expression (I), and thyroid NIS protein (J) levels in the cohort shown in B. (K) Plasma T4 levels in an independent cohort fed RD or HFD for 8 or 12 weeks. Data are shown as mean ± SEM; dots indicate individual mice. P values are shown in the graphs and were considered significant at P ≤ 0.05. One-way ANOVA followed by Dunnett’s correction and/or linear trend was used in B and E–J. Two-tailed Student’s t test was used in C, D, and K. Plasma total T4 (CSB-E05083m) and TSH (CSB-E05116m) were measured by ELISA (Cusabio). NIS antibody: MilliporeSigma (ABC1453).