School of Public Health (Shenzhen), Shenzhen Campus of Sun Yat-sen University, Shenzhen 518107, China.
School of Public Health (Shenzhen), Shenzhen Campus of Sun Yat-sen University, Shenzhen 518107, China; Guangdong Provincial Engineering Laboratory for Nutrition Translation, Guangzhou 510080, China; Guangdong Provincial Key Laboratory of Food, Nutrition and Health, Guangzhou 510080, China.
Biochim Biophys Acta Mol Basis Dis. 2024 Aug;1870(6):167246. doi: 10.1016/j.bbadis.2024.167246. Epub 2024 May 18.
Glucose and lipid metabolic disorders (GLMDs), such as diabetes, dyslipidemia, metabolic syndrome, nonalcoholic fatty liver disease, and obesity, are significant public health issues that negatively impact human health. The endoplasmic reticulum (ER) plays a crucial role at the cellular level for lipid and sterol biosynthesis, intracellular calcium storage, and protein post-translational modifications. Imbalance and dysfunction of the ER can affect glucose and lipid metabolism. As an essential trace element, selenium contributes to various human physiological functions mainly through 25 types of selenoproteins (SELENOs). At least 10 SELENOs, with experimental and/or computational evidence, are predominantly found on the ER membrane or within its lumen. Two iodothyronine deiodinases (DIOs), DIO1 and DIO2, regulate the thyroid hormone deiodination in the thyroid and some external thyroid tissues, influencing glucose and lipid metabolism. Most of the other eight members maintain redox homeostasis in the ER. Especially, SELENOF, SELENOM, and SELENOS are involved in unfolded protein responses; SELENOI catalyzes phosphatidylethanolamine synthesis; SELENOK, SELENON, and SELENOT participate in calcium homeostasis regulation; and the biological significance of thioredoxin reductase 3 in the ER remains unexplored despite its established function in the thioredoxin system. This review examines recent research advances regarding ER SELENOs in GLMDs and aims to provide insights on ER-related pathology through SELENOs regulation.
葡萄糖和脂质代谢紊乱（GLMDs），如糖尿病、血脂异常、代谢综合征、非酒精性脂肪性肝病和肥胖症，是严重影响人类健康的重大公共卫生问题。内质网（ER）在细胞水平上对于脂质和固醇生物合成、细胞内钙储存以及蛋白质翻译后修饰起着至关重要的作用。ER 的失衡和功能障碍会影响葡萄糖和脂质代谢。硒作为一种必需的微量元素，主要通过 25 种硒蛋白（SELENOs）参与各种人体生理功能。至少有 10 种 SELENOs，具有实验和/或计算证据，主要位于 ER 膜上或其腔室内。两种甲状腺素脱碘酶（DIOs），DIO1 和 DIO2，调节甲状腺和一些甲状腺外组织中的甲状腺激素脱碘，影响葡萄糖和脂质代谢。其他八个成员中的大多数维持 ER 中的氧化还原稳态。特别是，SELENOF、SELENOM 和 SELENOS 参与未折叠蛋白反应；SELENOI 催化磷脂酰乙醇胺合成；SELENOK、SELENON 和 SELENOT 参与钙稳态调节；尽管其在硫氧还蛋白系统中的功能已经确立，但 ER 中的硫氧还蛋白还原酶 3 的生物学意义仍未被探索。本综述考察了 ER SELENOs 在 GLMDs 中的最新研究进展，并旨在通过 SELENOs 调节提供对 ER 相关病理学的见解。
