EC. Akkaya, R. Ilgin, S. Kızıldağ, A. Argon and F. Hoşgörler (2026). Effects of Ketogenic Diet on Behavioral, Metabolic, and Peripheral Tissue Changes in a Propylthiouracil-Induced Hypothyroidism Model. Medical principles and practice : international journal of the Kuwait University, Health Science Centre, 1-10. https://doi.org/10.1159/000552101

PubMed 42102036

[Abstract]
OBJECTIVE: This study aimed to evaluate whether a ketogenic diet (KD) mitigates behavioral, metabolic, and peripheral tissue alterations in a rat model of propylthiouracil (PTU)-induced hypothyroidism.

SUBJECTS AND METHODS: Adult female Sprague-Dawley rats (n = 28) were randomly assigned to control, KD, PTU, and KD+PTU groups. Hypothyroidism was induced using 0.05% PTU for 6 weeks, while KD was administered during the final 4 weeks. Behavioral testing was conducted during the final phase of the experimental period, followed by biochemical and histological analyses at the end of the 6-week protocol. Behavioral assessments included the open field, light/dark box, forced swim, and Morris water maze tests. Biochemical analyses evaluated serum free thyroxine (T4), thyroid-stimulating hormone (TSH), glucose, β-hydroxybutyrate, tumor necrosis factor alpha (TNF-α), and interleukin 10 (IL-10). Histological evaluations targeted the thyroid gland, liver, white adipose tissue (WAT), and brown adipose tissue (BAT).

RESULTS: PTU significantly reduced serum free T4 levels and impaired spatial learning and mood-related behaviors. KD effectively induced nutritional ketosis and improved systemic glucose metabolism but did not reverse cognitive impairment or depressive-like behaviors associated with hypothyroidism. Histologically, KD attenuated PTU-induced hepatic inflammation, WAT dysfunction, and BAT whitening. Thyroid morphology and circulating TNF-α and IL-10 levels remained unchanged across groups.

CONCLUSION: KD exerts favorable metabolic and peripheral tissue effects in PTU-induced hypothyroidism but does not rescue associated neurobehavioral deficits, likely due to persistent thyroid hormone deficiency.