Overnutrition directly impairs thyroid hormone biosynthesis and utilization, causing hypothyroidism, despite...

Area of Science:

• Endocrinology
• Metabolic Regulation
• Obesity Research

Background:

• Thyroid hormones (THs) regulate metabolic rate and energy expenditure (EE).
• Hypothyroidism is linked to reduced EE and obesity, but the causal relationship is debated.
• Emerging evidence suggests obesity may induce thyroid dysfunction.

Purpose of the Study:

• To investigate the direct effects of diet-induced obesity on thyroid histopathology, function, and TH action in a mouse model.
• To determine if overnutrition impairs thyroid hormone biosynthesis and signaling.

Main Methods:

• A mouse model of diet-induced obesity was utilized.
• Thyroid histopathology, deiodinase activity, TH levels, and ER stress were assessed.
• Energy expenditure and response to T4 were measured.

Main Results:

• Overnutrition rapidly induced hypothyroidism, decreasing thyroidal THs and thyroglobulin.
• Thyroid ER stress and histological/vascular changes were observed.
• T4 activation was suppressed, leading to T4 resistance and reduced EE.

Conclusions:

• Overnutrition directly impairs thyroid hormone biosynthesis and action, causing hypothyroidism and reduced EE.
• Thyroid dysfunction in obese mice is reversible with weight loss.
• Human BMI correlates with thyroid vascularization, suggesting translatability and potential therapeutic targets.