ER stress contributes to high-fat diet-induced decrease of thyroglobulin and hypothyroidism

Abstract

Recent studies revealed the emerging role of excess uptake of lipids in the development of hypothyroidism. However, the underlying mechanism is largely unknown. We investigated the effect of high-fat diet (HFD) on thyroid function and the role of endoplasmic reticulum (ER) in HFD-induced hypothyroidism. Male Sprague-Dawley rats were fed with HFD or control diet for 18 wk. HFD rats showed an impaired thyroid function, with decreased thyroglobulin (Tg) level. We found the ER stress was triggered in HFD rat thyroid glands and palmitate-treated thyrocytes. Luminal swelling of ER in thyroid epithelial cells of HFD rats was also observed. The rate of Tg degradation increased in palmitate-treated thyrocytes. In addition, applying 4-phenyl butyric acid to alleviate ER stress in HFD rats improved the decrease of Tg and thyroid function. Withdrawal of the HFD improved thyroid function . In conclusion, we demonstrate that ER stress mediates the HFD-induced hypothyroidism, probably by impairing the production of Tg, and attenuation of ER stress improves thyroid function. Our study provides the understanding of how HFD induces hypothyroidism.

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.…”

Thyroid hormone synthesis continues despite biallelic thyroglobulin mutation with cell death

“…The synthesis of misfolded Tg is accompanied by ER stress (38,(48)(49)(50)(51). Ongoing ER stress in the thyroids of TG cog/cog mice was demonstrable (Fig.…”

Bile acid toxicity in Paneth cells contributes to gut dysbiosis induced by high-fat feeding

“…By virtue of their highly secretory function, Paneth cells are characterized by extensive networks of ER and thus are particularly susceptible to increased ER stress response and autophagy ( 45 ). Prior reports have demonstrated that a HFD and obesity induce ER stress in different organ systems, including adipose tissue, the amygdala, and the thyroid gland ( 46 – 48 ). Guo et al reported increased mRNA expression of ER stress markers, including BiP , activating transcription factor 4 ( ATF4 ), and c/EBP-homologous protein ( CHOP ) in mice fed a HFD ( 49 ).…”