Zinc mediates the SREBP-SCD axis to regulate lipid metabolism in Caenorhabditis elegans[S]

Autor: Jing-Jing Zhang, Jun-Jun Hao, Yu-Ru Zhang, Yan-Li Wang, Ming-Yi Li, Hui-Lai Miao, Xiao-Ju Zou, Bin Liang
Jazyk: angličtina
Rok vydání: 2017
Předmět:
Zdroj: Journal of Lipid Research, Vol 58, Iss 9, Pp 1845-1854 (2017)
Druh dokumentu: article
ISSN: 0022-2275
DOI: 10.1194/jlr.M077198
Popis: Maintenance of lipid homeostasis is crucial for cells in response to lipid requirements or surplus. The SREBP transcription factors play essential roles in regulating lipid metabolism and are associated with many metabolic diseases. However, SREBP regulation of lipid metabolism is still not completely understood. Here, we showed that reduction of SBP-1, the only homolog of SREBPs in Caenorhabditis elegans, surprisingly led to a high level of zinc. On the contrary, zinc reduction by mutation of sur-7, encoding a member of the cation diffusion facilitator (CDF) family, restored the fat accumulation and fatty acid profile of the sbp-1(ep79) mutant. Zinc reduction resulted in iron overload, which thereby directly activated the conversion activity of stearoyl-CoA desaturase (SCD), a main target of SREBP, to promote lipid biosynthesis and accumulation. However, zinc reduction reversely repressed SBP-1 nuclear translocation and further downregulated the transcription expression of SCD for compensation. Collectively, we revealed zinc-mediated regulation of the SREBP-SCD axis in lipid metabolism, distinct from the negative regulation of SREBP-1 or SREBP-2 by phosphatidylcholine or cholesterol, respectively, thereby providing novel insights into the regulation of lipid homeostasis.
Databáze: Directory of Open Access Journals