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

Appl Physiol Nutr Metab. 2018 Apr;43(4):371-380. doi: 10.1139/apnm-2017-0410. Epub 2017 Nov 3.

Abstract

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. TRHR1 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, TRHR2 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.

Keywords: C57BL/6J mice; HFSC feed; ObR; T3; TRH; TRH receptors; TSH; axe HPT (hypothalamus–pituitary–thyroid); glande thyroïde; hypothalamus–pituitary–thyroid (HPT) axis; metabolic syndrome; p-STAT3; récepteurs TRH; régime HFSC; souris C57BL/6J; syndrome métabolique; thyroid gland.

MeSH terms

  • Animals
  • Diet, High-Fat*
  • Dietary Carbohydrates*
  • Hypothalamo-Hypophyseal System / metabolism*
  • Hypothalamo-Hypophyseal System / physiopathology
  • Male
  • Mice, Inbred C57BL
  • Phosphorylation
  • 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
  • STAT3 Transcription Factor / metabolism
  • Thyroid Gland / metabolism*
  • Thyroid Gland / physiopathology
  • Thyroid Gland / ultrastructure
  • Thyrotropin / blood
  • Thyrotropin-Releasing Hormone / genetics
  • Thyrotropin-Releasing Hormone / metabolism
  • Time Factors
  • Triiodothyronine / blood

Substances

  • Dietary Carbohydrates
  • Mlnr protein, rat
  • Receptors, G-Protein-Coupled
  • Receptors, Leptin
  • Receptors, Thyrotropin-Releasing Hormone
  • STAT3 Transcription Factor
  • Stat3 protein, rat
  • Triiodothyronine
  • Thyrotropin-Releasing Hormone
  • Thyrotropin