RRC ID 51439
著者 Zhang JJ, Hao JJ, Zhang YR, Wang YL, Li MY, Miao HL, Zou XJ, Liang B.
タイトル Zinc mediates the SREBP-SCD axis to regulate lipid metabolism in Caenorhabditis elegans.
ジャーナル J Lipid Res
Abstract 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.
巻・号 58(9)
ページ 1845-1854
公開日 2017-9-1
DOI 10.1194/jlr.M077198
PII S0022-2275(20)33955-9
PMID 28710073
PMC PMC5580898
MeSH Adipose Tissue / metabolism Animals Caenorhabditis elegans / enzymology Caenorhabditis elegans / genetics Caenorhabditis elegans / metabolism* Caenorhabditis elegans Proteins / genetics Caenorhabditis elegans Proteins / metabolism* Genomics Lipid Metabolism* Mutation Stearoyl-CoA Desaturase / metabolism* Sterol Regulatory Element Binding Protein 1 / genetics Sterol Regulatory Element Binding Protein 1 / metabolism* Transcription Factors / genetics Transcription Factors / metabolism* Zinc / metabolism*
IF 4.483
引用数 8
リソース情報
線虫 tm6523