Palmitic Acid Downregulates Thyroglobulin (Tg), Sodium Iodide Symporter (NIS), and Thyroperoxidase (TPO) in Human Primary Thyrocytes: A Potential Mechanism by Which Lipotoxicity Affects Thyroid?

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.

Relation of Gut Microbes and L-Thyroxine Through Altered Thyroxine Metabolism in Subclinical Hypothyroidism Subjects

“…On the other hand, our previous reports had established the potential effects of excess lipid deposition to thyroid function, by which the probable mechanism was lipotoxicity-related endoplasmic reticulum (ER) stress or mitochondrial stress of thyrocytes, subsequently leading to thyroid dysfunction. This is an innovative point of view that had been confirmed in clinical study and laboratory research (Zhao et al, 2016 , 2018 ; Zhang et al, 2019 ). In this study, gut microbes, which had already been recognized as another important “endocrine factors,” was the focus to discover the possible association with SCH on clinical levels.…”

Association between different obesity phenotypes and hypothyroidism: a study based on a longitudinal health management cohort

“…Another possible explanation is that the thyroid might be a target organ affected by lipotoxicity [ 35 – 39 ]. Our previous study found that palmitic acid could downregulate the expression and activity of three key molecules in thyroid hormone synthesis (NIS, thyroglobulin, and thyroperoxidase) in human primary thyrocytes [ 36 ]. Endoplasmic reticulum stress might play a role in high-fat diet-induced hypothyroidism [ 38 ].…”

Statin Use and Benefits of Thyroid Function: A Retrospective Cohort Study

“…Increasing evidence has shown that the disturbance of lipid metabolism might play a role in the pathogenesis of thyroid dysfunction (5)(6)(7)(8)24). As one kind of lipid components, cholesterol might also affect thyroid function, just like saturated fats.…”

“…In recent years, studies have revealed the emerging role of the disturbance of lipid metabolism in the development of hypothyroidism (4)(5)(6)(7)(8)(9). Our previous prospective observational study found that high baseline total cholesterol (TC) level was a risk factor of progression to OH in patients with SCH (10), which suggested that cholesterol may influence thyroid function.…”