High-fat, simple-carbohydrate diet intake induces hypothalamic–pituitary–thyroid axis dysregulation in C57BL/6J male mice

• Published in: Applied physiology, nutrition, and metabolism Vol. 43; no. 4; pp. 371 - 380
• Main Authors: Swarnalatha, Nagaraj Banavara, Roy, Neena, Gouda, Mahesh Manjunath, Moger, Rajeish, Abraham, Asha
• Format: Journal Article
• Language: English
• Published: Canada NRC Research Press 01.04.2018; Canadian Science Publishing NRC Research Press
• Subjects: Analysis; Animals; axe HPT (hypothalamus–pituitary–thyroid); C57BL/6J mice; Carbohydrates; Diet; Diet, High-Fat; Dietary Carbohydrates; Gene expression; glande thyroïde; Health aspects; HFSC feed; High fat diet; Hypothalamo-Hypophyseal System - metabolism; Hypothalamo-Hypophyseal System - physiopathology; hypothalamus–pituitary–thyroid (HPT) axis; Hypothyroidism; Male; Metabolic syndrome; Metabolism; Mice, Inbred C57BL; ObR; Oils & fats; p-STAT3; Phosphorylation; Pituitary gland; Receptors, G-Protein-Coupled - genetics; Receptors, G-Protein-Coupled - metabolism; Receptors, Leptin - genetics; Receptors, Leptin - metabolism; Receptors, Thyrotropin-Releasing Hormone - genetics; Receptors, Thyrotropin-Releasing Hormone - metabolism; Risk factors; Rodents; récepteurs TRH; régime HFSC; souris C57BL/6J; STAT3 Transcription Factor - metabolism; syndrome métabolique; Thyroid gland; Thyroid Gland - metabolism; Thyroid Gland - physiopathology; Thyroid Gland - ultrastructure; Thyrotropin - blood; Thyrotropin-Releasing Hormone - genetics; Thyrotropin-Releasing Hormone - metabolism; Time Factors; TRH; TRH receptors; Triiodothyronine - blood; TSH; India; axe HPT (hypothalamus–pituitary–thyroid); régime HFSC; TSH; thyroid gland; récepteurs TRH; TRH; glande thyroïde; HFSC feed; hypothalamus–pituitary–thyroid (HPT) axis; metabolic syndrome; syndrome métabolique; C57BL/6J mice; TRH receptors; souris C57BL/6J; ObR; p-STAT3; T3
• ISSN: 1715-5312; 1715-5320
• DOI: 10.1139/apnm-2017-0410

Given the association between subclinical hypothyroidism and metabolic syndrome, we wanted to explore if high-fat, simple-carbohydrate (HFSC) diet affects hypothalamus–pituitary–thyroid axis. One-month-old male C57BL/6J mice were fed with control (C) and HFSC (T) feed (n = 18 each), respectively, for 5 months. There was a significant increase in triiodothyronine in the T group (13.5%) compared with the age-matched C group by the fifth month. Thyroid-stimulating hormone was significantly higher (1 month: 1.9-fold; 3 months: 2.66-fold; 5 months: 3.5-fold) from the first to fifth months in the T group compared with age-matched C group. Thyrotropin-releasing hormone (TRH) gene expression showed significant decrease (1 month: 83.2%; 5 months: 40.7%) in the T group compared with the age-matched C group. TRHR 1 showed significant decrease in the T group compared with the age-matched C group throughout the study (1 month: 82.8%; 3 months: 45.7%; 5 months: 75.2%). However, TRHR 2 showed dynamic change during the study. Initially there was significant (1 month: 0.104-fold) downregulation, followed by significant upregulation (3 months: 3.6-fold) and downregulation (0.73-fold) by the fifth month in the T group compared with the age-matched C group. There was marked depletion of functional follicular cells and colloid substance in the thyroid glands of the T group by the fifth month compared with the C group. Leptin receptors ObRa (1 month: 48.25%; 5 months: 88%) and ObRb (1 month: 46.9%; 5 months: 63.3%) were significantly downregulated in the T group compared with the age-matched C group in the first and fifth months of feeding the respective diets. The expression of p-STAT3, a transcription factor known to have a role in energy balance, intermediate metabolism, and leptin signalling was seen to decrease significantly (6.25-fold) in the hypothalamus of the T group compared with the age-matched C group. In conclusion, HFSC feed disrupts the hypothalamus–pituitary–thyroid axis in male C57BL/6J mice.