Journal Article Epublish
PubMed: 40244197 DOI: 10.3390/ijms26073363
Ablation of Mouse Selenium-Binding Protein 1 and 2 Elevates LDL by Disruption of Cholesterol Efflux and Lipid Metabolism.
Int J Mol Sci 26(7)
Authors: Shuangli Zhao, Yingxia Song, Yuko Nakashima, Xing Zou, Takayuki Koga, Takumi Ishida, Renshi Li, Yuko Hirota, Yoshitaka Tanaka, Yuji Ishii
Affiliations
- Division of Pharmaceutical Cell Biology, Graduate School of Pharmaceutical Sciences, Kyushu University, Fukuoka 812-8582, Japan.
- Laboratory of Hygienic Chemistry, Daiichi University of Pharmacy, Fukuoka 815-8511, Japan.
- School of Pharmacy, International University of Health and Welfare Fukuoka, Ohkawa 831-8501, Japan.
- School of Traditional Chinese Pharmacy, China Pharmaceutical University, Nanjing 211198, China.
Abstract
Selenium-binding protein 1 (SeBP1) is an anticancer factor that affects lipid metabolism in mouse kidneys via the peroxisome proliferator-activated receptor-alpha (PPARA) pathway. However, its physiological role in the liver is difficult to explain because of the presence of the highly homologous selenium-binding protein 2 (SeBP2). To investigate the role of these proteins in the liver, we generated and double-knockout mice (-DK). deletion did not significantly alter the mice phenotypic compared to that of the wild-type strain. Then, we identified the genes involved in hepatic lipid metabolism. The double knockout did not affect fatty acid and cholesterol synthesis, but inhibited fatty acid oxidation and cholesterol efflux. Furthermore, transfection of HepG2 cells with human selenium-binding protein 1 (hSeBP1) positively regulated PPARA and the genes controlled by it. Overexpression of hSeBP1 reduced the levels of non-esterified fatty acids in the culture medium. The serum levels of low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, and triglycerides were significantly different among the three groups. In summary, we elucidated the potential signaling pathways of SeBP1 and SeBP2 in fatty acid oxidation and hepatic cholesterol efflux. Our findings provide insights relevant for developing new strategies to prevent and treat lipid metabolism disorders.
MeSH
Genes, Lipoproteins, Liver, Cholesterol, Selenium-Binding Proteins, Triglycerides, Fatty Acids