Department of Biochemistry
Iowa City, IA 52242-1109 USA
fax: (319) 335-9570
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Brandon Davies, PhD
Carver College of Medicine
University of Iowa
51 Newton Rd, 4-370 BSB
Iowa City, IA 52242
Lab Phone: 335-3228
Our lab studies the role of endothelial cells in lipid metabolism. The lipolytic processing of triglyceride-rich lipoproteins in the bloodstream by lipoprotein lipase (LPL) is the central event in plasma lipid metabolism. Acting inside capillaries, LPL cleaves lipoprotein triglycerides, releasing fatty acids that are taken up by tissues and either used for fuel or stored in cytosolic lipid droplets. LPL is synthesized by parenchymal cells (e.g. myocytes and adipocytes) and secreted into the interstitial spaces, but to be functional in processing triglycerides in the plasma, it must be transported to the capillary lumen. The endothelial cell protein GPIHBP1 serves as the LPL transporter, capturing LPL and moving it across endothelial cells to the capillary lumen. When GPIHBP1 is absent, LPL cannot reach the capillary lumen, leading to severe hypertriglyceridemia (in both humans and mice).
Figure 1. Lipoprotein lipase is synthesized and secreted by myocytes and adipocytes. Secreted LPL binds GPIHBP1 on the basolateral surface of endothelial cells and transported to the capillary lumen where LPL hydrolyzes the triglycerides of circulating lipoproteins.
The identification of GPIHBP1 as the LPL transporter provided novel evidence that endothelial cells play an active role in plasma lipid metabolism. Maintaining metabolic homeostasis requires moving nutrients, hormones, and enzymes across capillary endothelial cells. Yet, how endothelial cell function is controlled so that metabolic activity inside capillaries and the delivery of nutrients across endothelial cells matches the needs of the underlying tissues has not been adequately explored. To address this issue, we study the mechanisms and regulation of trans-endothelial transport as it relates to lipid metabolism. We also study how the expression of capillary specific proteins, such as GPIHBP1, is controlled in an effort to learn how the metabolic needs of specific tissues influence gene expression in the capillaries servicing those tissues.
- Davies BS, Goulbourne CN, Barnes RH, 2nd, Turlo KA, Gin P, Vaughan S, Vaux DJ, Bensadoun A, Beigneux AP, Fong LG, Young SG. Assessing mechanisms of GPIHBP1 and lipoprotein lipase movement across endothelial cells. Journal of Lipid Research. 2012;53:2690-2697.
Jung HJ, Coffinier C, Choe Y, Beigneux AP, Davies BSJ, Yang SH, Barnes II RH, Hong J, Sun T, Pleasure SJ. Regulation of prelamin A but not lamin C by miR-9, a brain-specific microRNA. Proceedings of the National Academy of Sciences. 2012;109(7):E423-E31.
Davies BSJ, Beigneux AP, Fong LG, Young SG. New wrinkles in lipoprotein lipase biology. Current Opinion in Lipidology. 2012;23(1):35.
Voss CV, Davies BSJ, Tat S, Gin P, Fong LG, Pelletier C, Mottler CD, Bensadoun A, Beigneux AP, Young SG. Mutations in lipoprotein lipase that block binding to the endothelial cell transporter GPIHBP1. Proceedings of the National Academy of Sciences. 2011;108(19):7980.
Davies BSJ, Coffinier C, Yang SH, Barnes RH. Investigating the purpose of prelamin A processing. Nucleus. 2011;2(1):4.
Beigneux AP, Davies BSJ, Tat S, Chen J, Gin P, Voss CV, Weinstein MM, Bensadoun A, Pullinger CR, Fong LG. Assessing the role of the glycosylphosphatidylinositol-anchored high density lipoprotein-binding protein 1 (GPIHBP1) three-finger domain in binding lipoprotein lipase. Journal of Biological Chemistry. 2011;286(22):19735.
Davies BSJ, Beigneux AP, Barnes Ii RH, Tu Y, Gin P, Weinstein MM, Nobumori C, Nyren R, Goldberg I, Olivecrona G. GPIHBP1 is responsible for the entry of lipoprotein lipase into capillaries. Cell Metabolism. 2010;12(1):42-52.
Davies BSJ, Barnes Ii RH, Tu Y, Ren S, Andres DA, Spielmann HP, Lammerding J, Wang Y, Young SG, Fong LG. An accumulation of non-farnesylated prelamin A causes cardiomyopathy but not progeria. Human Molecular Genetics. 2010;19(13):2682-94.
Davies BSJ, Fong LG, Yang SH, Coffinier C, Young SG. The posttranslational processing of prelamin A and disease. Annual Review of Genomics and Human Genetics. 2009;10:153.
Davies BSJ, Waki H, Beigneux AP, Farber E, Weinstein MM, Wilpitz DC, Tai LJ, Evans RM, Fong LG, Tontonoz P. The expression of GPIHBP1, an endothelial cell binding site for lipoprotein lipase and chylomicrons, is induced by peroxisome proliferator-activated receptor-Œ≥. Molecular Endocrinology. 2008;22(11):2496-504.
Beigneux AP, Davies BSJ, Gin P, Weinstein MM, Farber E, Qiao X, Peale F, Bunting S, Walzem RL, Wong JS. Glycosylphosphatidylinositol-anchored high-density lipoprotein-binding protein 1 plays a critical role in the lipolytic processing of chylomicrons. Cell Metabolism. 2007;5(4):279-91.
Davies BS, Goulbourne CN, Barnes RH, 2nd, Turlo KA, Gin P, Vaughan S, Vaux DJ, Bensadoun A, Beigneux AP, Fong LG, Young SG. Assessing mechanisms of GPIHBP1 and lipoprotein lipase movement across endothelial cells. Journal of Lipid Research. 2012;53:2690-2697.
- Visit Google Scholar for all of Dr. Brandon Davies's publications.
Fraternal Order of Eagles Diabetes Research Center (FOEDRC)
University of Iowa Obesity Research and Education Initiative
Molecular and Cellular Biology Program (MCB)
Medical Scientist Training Program (MSTP)
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