Effects of Ketogenic Diet on Behavioral, Metabolic, and Peripheral Tissue Changes in a Propylthiouracil-Induced Hypothyroidism Model


AKKAYA E. C., Ilgin R., KIZILDAĞ S., Argon A., HOŞGÖRLER F. U.

MEDICAL PRINCIPLES AND PRACTICE, 2026 (SCI-Expanded, Scopus)

  • Yayın Türü: Makale / Tam Makale
  • Basım Tarihi: 2026
  • Doi Numarası: 10.1159/000552101
  • Dergi Adı: MEDICAL PRINCIPLES AND PRACTICE
  • Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus, CINAHL, EMBASE, MEDLINE, Directory of Open Access Journals, Academic Search Ultimate (EBSCO), Health Research Premium Collection (ProQuest)
  • Dokuz Eylül Üniversitesi Adresli: Evet

Özet

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, beta-hydroxybutyrate, tumor necrosis factor alpha (TNF-alpha), 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-alpha 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.