College of Food Science and Technology, Yunnan Agricultural University, Kunming 650201, China.
Center for Life Sciences, School of Life Sciences, Yunnan University, Kunming, Yunnan 650091, China.
G3 (Bethesda). 2021 Jul 14;11(7). doi: 10.1093/g3journal/jkab120.
Zinc is one of the most important trace elements as it plays a vital role in many biological processes. As well, aberrant zinc metabolism has been implicated in lipid-related metabolic diseases. Previously, we showed that zinc antagonizes iron to regulate sterol regulatory element-binding proteins and the stearoyl-CoA desaturase (SREBP-SCD) pathway in lipid metabolism in the model organism Caenorhabditis elegans. In this study, we present the identification of another cation diffusion facilitator, CDF-1, which regulates lipid metabolism along with SUR-7 in response to zinc. Inactivation of SBP-1, the only homolog of SREBPs, leads to an increased zinc level but decreased lipid accumulation. However, either the cdf-1(n2527) or sur-7(tm6523) mutation could successfully restore the altered fatty acid profile, fat content, and zinc level of the sbp-1(ep79) mutant. Furthermore, we found that CDF-1/SUR-7 may functionally bypass SBP-1 to directly affect the conversion activity of SCD in the biosynthesis of unsaturated fatty acids and lipid accumulation. Collectively, these results consistently support the link between zinc homeostasis and lipid metabolism via the SREBP-SCD axis by the cation diffusion facilitators CDF-1 and SUR-7.
锌是最重要的微量元素之一，因为它在许多生物过程中起着至关重要的作用。此外，异常的锌代谢与脂质相关的代谢疾病有关。之前，我们表明锌拮抗铁来调节固醇调节元件结合蛋白和硬脂酰辅酶 A 去饱和酶（SREBP-SCD）途径在脂质代谢中的模型生物秀丽隐杆线虫。在这项研究中，我们鉴定了另一种阳离子扩散促进剂 CDF-1，它与 SUR-7 一起响应锌调节脂质代谢。唯一 SREBPs 的同源物 SBP-1 的失活导致锌水平增加但脂质积累减少。然而，cdf-1(n2527)或 sur-7(tm6523)突变都可以成功地恢复 sbp-1(ep79)突变体改变的脂肪酸谱、脂肪含量和锌水平。此外，我们发现 CDF-1/SUR-7 可能通过阳离子扩散促进剂 CDF-1 和 SUR-7 绕过 SBP-1 直接影响 SCD 在不饱和脂肪酸生物合成和脂质积累中的转化活性。总的来说，这些结果一致支持通过阳离子扩散促进剂 CDF-1 和 SUR-7 维持锌稳态和脂质代谢之间的联系通过 SREBP-SCD 轴。
