Gpihbp1-KO Mouse

Gpihbp1, short for glycosylphosphatidylinositol-anchored HDL binding protein 1, is a GPI-anchored protein in capillary endothelial cells. It is crucial for the lipolytic processing of triglyceride-rich lipoproteins (TRLs) [3]. Gpihbp1 shuttles lipoprotein lipase (LPL) to the capillary lumen, enabling lipid metabolism and the margination of lipoproteins along capillaries, which is essential for plasma triglyceride metabolism [2,3,4,5,6,7,8].

Gpihbp1 knockout mice exhibit chylomicronemia, even on a low-fat diet, with plasma triglyceride levels as high as 3,500-5,000 mg/dl [7]. This indicates that Gpihbp1 is required for the normal lipolytic processing of TRLs. The abnormal pattern of LPL release into the plasma after heparin injection in Gpihbp1-deficient mice suggests Gpihbp1 plays a direct role in binding LPL within tissues [8]. Also, in some cases, chylomicronemia in humans is caused by autoantibodies against Gpihbp1, which prevent the binding and transport of LPL by Gpihbp1, disrupting the lipolytic processing of TRLs [1].

In conclusion, Gpihbp1 is essential for the lipolytic processing of triglyceride-rich lipoproteins by shuttling LPL to the capillary lumen. The study of Gpihbp1 knockout mouse models has been instrumental in revealing its role in plasma triglyceride metabolism and in understanding the pathogenesis of chylomicronemia, highlighting its importance in these disease-related biological processes [1,3,7,8].

References:

1. Miyashita, Kazuya, Lutz, Jens, Hudgins, Lisa C, Young, Stephen G, Beigneux, Anne P. 2020. Chylomicronemia from GPIHBP1 autoantibodies. In Journal of lipid research, 61, 1365-1376. doi:10.1194/jlr.R120001116. https://pubmed.ncbi.nlm.nih.gov/32948662/

2. Jiang, Shali, Ren, Zhuoqun, Yang, Yutao, Zhou, Shenghua, Xiao, Yichao. 2023. The GPIHBP1-LPL complex and its role in plasma triglyceride metabolism: Insights into chylomicronemia. In Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie, 169, 115874. doi:10.1016/j.biopha.2023.115874. https://pubmed.ncbi.nlm.nih.gov/37951027/

3. Fong, Loren G, Young, Stephen G, Beigneux, Anne P, Jiang, Haibo, Ploug, Michael. 2016. GPIHBP1 and Plasma Triglyceride Metabolism. In Trends in endocrinology and metabolism: TEM, 27, 455-469. doi:10.1016/j.tem.2016.04.013. https://pubmed.ncbi.nlm.nih.gov/27185325/

4. Young, Stephen G, Fong, Loren G, Beigneux, Anne P, Birrane, Gabriel, Ploug, Michael. . GPIHBP1 and Lipoprotein Lipase, Partners in Plasma Triglyceride Metabolism. In Cell metabolism, 30, 51-65. doi:10.1016/j.cmet.2019.05.023. https://pubmed.ncbi.nlm.nih.gov/31269429/

5. Young, Stephen G, Davies, Brandon S J, Voss, Constance V, Fong, Loren G, Beigneux, Anne P. 2011. GPIHBP1, an endothelial cell transporter for lipoprotein lipase. In Journal of lipid research, 52, 1869-84. doi:10.1194/jlr.R018689. https://pubmed.ncbi.nlm.nih.gov/21844202/

6. Young, Stephen G, Davies, Brandon S J, Fong, Loren G, Bensadoun, André, Beigneux, Anne P. . GPIHBP1: an endothelial cell molecule important for the lipolytic processing of chylomicrons. In Current opinion in lipidology, 18, 389-96. doi:. https://pubmed.ncbi.nlm.nih.gov/17620854/

7. Beigneux, Anne P, Davies, Brandon S J, Bensadoun, André, Fong, Loren G, Young, Stephen G. 2008. GPIHBP1, a GPI-anchored protein required for the lipolytic processing of triglyceride-rich lipoproteins. In Journal of lipid research, 50 Suppl, S57-62. doi:10.1194/jlr.R800030-JLR200. https://pubmed.ncbi.nlm.nih.gov/18854402/

8. Beigneux, Anne P, Weinstein, Michael M, Davies, Brandon S J, Fong, Loren G, Young, Stephen G. . GPIHBP1 and lipolysis: an update. In Current opinion in lipidology, 20, 211-6. doi:10.1097/MOL.0b013e32832ac026. https://pubmed.ncbi.nlm.nih.gov/19369870/