Abstract
Our previous studies suggested that the thyroid might be a target organ affected by lipotoxicity, which might be partially related to the increasing prevalence of subclinical hypothyroidism. However, the underlying molecular mechanism is not yet clearly established. This study aimed to assess the effect of palmitic acid stimulation on thyrocyte function. Upon palmitic acid stimulation, intracellular contents of lipids, as well as the expression and activity of three key molecules in thyroid hormone synthesis (i.e., thyroglobulin, sodium iodide symporter, and thyroperoxidase), were determined in human primary thyrocytes. The contents of BODIPY® FL C16 (the fluorescently labeled palmitic acid analogue) entering into the thyrocytes were gradually increased with time extending. Accordingly, the intracellular accumulation of both triglyceride and free fatty acids increased in dose- and time-dependent manners. The effect of palmitic acid stimulation on thyroid hormone synthesis was then determined. Both the mRNA and protein levels of thyroglobulin, sodium iodide symporter, and thyroperoxidase were decreased following palmitic acid stimulation. Consistently, upon palmitic acid stimulation, the secreted thyroglobulin levels in supernatants, 131I uptake, and extracellular thyroperoxidase activity were all decreased in a dose-dependent manner. Our results demonstrated that upon palmitic acid stimulation, the expressions of the key molecules (thyroglobulin, sodium iodide symporter, and thyroperoxidase) were reduced and their activities were suppressed, which might lead to impaired thyroid hormone synthesis.
Highlights
Hypothyroidism, which is defined as failure of thyroid gland to produce sufficient thyroid hormone to meet the metabolic demands of the body, does affect a considerable proportion of the population [1,2,3,4]
palmitic acid (PA), the most abundant saturated fatty acid found in diets and bloodstream, is well known to induce lipotoxic effect in various nonadipose cells and often employed to study the potential molecular mechanisms of cellular damage generated by lipotoxicity [18]
We determined whether PA was able to enter the human primary thyrocytes, which might be a prerequisite for lipotoxicity
Summary
Hypothyroidism, which is defined as failure of thyroid gland to produce sufficient thyroid hormone to meet the metabolic demands of the body, does affect a considerable proportion of the population [1,2,3,4]. A survey carried out in 10 cities in China indicated that the prevalence of hypothyroidism had dramatically increased from 4.33% in 1999 to 17.73% in 2011 [5]. Risk factors contributing to the increasing prevalence of hypothyroidism have not been fully confirmed. Lipotoxicity has attracted great attention worldwide for its serious and extensive impact on human health. Lipotoxicity has been well documented in the pathogenesis of type 2 diabetes mellitus, metabolic syndrome, and nonalcoholic fatty liver disease [7, 8]. In the early 1990s, lipotoxicity induced by dietary fat overload
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