Diet’s rapid effects on the thyroid gland challenge unidirectional assumptions about hypothyroidism and energy balance

Thyroid hormones provide crucial regulation of energy expenditure through their effects on thermogenesis, lipid metabolism, and mitochondrial function. Given their close relationship with overall metabolism, a deficit in thyroid hormones fittingly leads to a positive energy balance and weight gain. The direction of this process may also operate in reverse, according to recent research from Rampy et al. in this issue of JCI. These investigators found that mice introduced to a high-fat, high-sugar diet developed marked short-term intracellular stress and functional impairment in the thyroid gland, leading to alterations in serum thyroid hormone levels prior to measurable weight gain. This finding opens the possibility that thyroid dysfunction originates from persistent damage to the thyroid gland caused by sustained overnutrition.