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Department of Cell Biology Faculty
Xian-cheng Jiang, Ph.D.
Department of Cell Biology, Box 5
Tel: (718) 270-6701 • Fax: (718) 270-3732
Lipid Metabolism and Metabolic Diseases
Research Interests: The primary interest of my laboratory is to investigate the effect of lipid metabolism and metabolic diseases, such as atherosclerosis, metabolic syndrome, obesity, and liver steatosis. We are particularly interested in understanding how phospholipid metabolism influences plasma lipoprotein metabolism, cell membrane lipid composition and function, and the development of metabolic diseases.
We have three on-going specific aspects:
1). Sphingomyelin biosynthesis. Sphingomyelin is one of the major phospholipids on the cell membrane and in the circulation. The biochemical synthesis of sphingomylin occurs through the actions of serine palmitoyl-CoA transferase (SPT), 3-ketosphinganine reductase, ceramide synthase, dihydroceramide desaturase and sphingomyelin synthase (SMS). We are studying the impact of SPT and SMS activity on lipid metabolism and disease development, using systemic gene knockout or overexpression, and tissue specific gene knockout or overexpression approaches.
2). Phosphotidycholine (PC) remodeling. PC is the major lipid on cell membrane and all plasma lipoproteins. PCs are first synthesized from glycerol-3-phosphate in the de novo pathway, and undergo maturation in the remodeling pathway, as reported by Lands (Lands’ cycle). The remodeling process, which concerns the turnover of about half of the PC molecules, involves the deacylation of PC to lysophosphatidylcholine (lysoPC), followed by reacylation of lysoPC to PC. The deacylation is catalyzed by calcium independent phospholipase A2 (iPLA2) and the reacylation is catalyzed by lysophosphatidylcholine acyltransferase (LPCAT). We are studying LPCAT function, using systemic or tissue specific gene knock out mouse models.
3). Phospholipid transfer protein (PLTP). PLTP is an independent risk factor for human coronary artery diseases. In mouse models, it has been shown that systemic PLTP deficiency reduces atherosclerosis, while its overexpression demonstrates the opposite effect. Therefore, PLTP is considered a promising target for pharmacological intervention in atherosclerosis. However, the mechanisms involved in these reactions are not entirely clear. For better understanding of them, we are evaluating the effect of PLTP on lipoprotein production, using mouse models (systemic or tissue specific knockout) available in our laboratory.
SELECTED RECENT PUBLICATIONS
Jeong Ts, Schissel SL, Tabas I, Pownall HJ, Tall AR, Jiang XC. Increased sphingomyelin content of plasma lipoproteins in apolipoprotein E knockout mice reflects combined production and catabolic defects and enhances reactivity with mammalian sphingomyelinase. J Clin Invest. 1998;101:905-12
Jiang XC, Bruce C, Mar J, Lin M, Ji Y, Francone OL, Tall AR. Targeted mutation of plasma phospholipid transfer protein gene markedly reduces high-density lipoprotein levels. J Clin Invest. 1999;103:907-14.
Kawano K, Qin SC, Lin M, Tall AR, Jiang XC. Cholesteryl ester transfer protein and phospholipid transfer protein have nonoverlapping functions in vivo. J Biol Chem. 2000;275:29477-81.
Jiang XC, Paultre F, Pearson TA, Reed RG, Francis CK, Lin M, Berglund L, Tall AR. Plasma sphingomyelin level as a risk factor for coronary artery disease. Arterioscler Thromb Vasc Biol. 2000;20:2614-8.
Jiang XC, Qin S, Qiao C, Kawano K, Lin M, Skold A, Xiao X, Tall AR. Apolipoprotein B secretion and atherosclerosis are decreased in mice with phospholipid-transfer protein deficiency. Nat Med. 2001;7:847-52. Erratum in: Nat Med 2001;7:973.
Jiang XC, Tall AR, Qin S, Lin M, Schneider M, Lalanne F, Deckert V, Desrumaux C, Athias A, Witztum JL, Lagrost L. Phospholipid transfer protein deficiency protects circulating lipoproteins from oxidation due to the enhanced accumulation of vitamin E. J Biol Chem. 2002;277:31850-6
Cao G, Beyer TP, Yang XP, Schmidt RJ, Zhang Y, Bensch WR, Kauffman RF, Gao H, Ryan TP, Liang Y, Eacho PI, Jiang XC. Phospholipid transfer protein is regulated by liver X receptors in vivo. J Biol Chem. 2002;277:39561-5.
Jiang XC, Beyer TP, Li Z, Liu J, Quan W, Schmidt RJ, Zhang Y, Bensch WR, Eacho PI, Cao G. Enlargement of high density lipoprotein in mice via liver X receptor activation requires apolipoprotein E and is abolished by cholesteryl ester transfer protein expression. J Biol Chem. 2003;278:49072-8.
Hojjati MR, Li Z, Zhou H, Tang S, Huan C, Ooi E, Lu S, Jiang XC. Effect of myriocin on plasma sphingolipid metabolism and atherosclerosis in apoE-deficient mice. J Biol Chem. 2005;280:10284-9.
Jiang XC, Li Z, Liu R, Yang XP, Pan M, Lagrost L, Fisher EA, Williams KJ Phospholipid transfer protein deficiency impairs apolipoprotein-B secretion from hepatocytes by stimulating a proteolytic pathway through a relative deficiency of vitamin E and an increase in intracellular oxidants. J Biol Chem. 2005;280:18336-40.
Liu R, Hojjati MR, Devlin CM, Hansen IH, Jiang XC. Macrophage phospholipid transfer protein deficiency and ApoE secretion: impact on mouse plasma cholesterol levels and atherosclerosis. Arterioscler Thromb Vasc Biol. 2007;27:190-6.
Liu R, Iqbal J, Yeang C, Wang DQ, Hussain MM, Jiang XC. Phospholipid transfer protein-deficient mice absorb less cholesterol. Arterioscler Thromb Vasc Biol. 2007;27:2014-21.
Hailemariam TK, Huan C, Liu J, Li Z, Roman C, Kalbfeisch M, Bui HH, Peake DA, Kuo MS, Cao G, Wadgaonkar R, Jiang XC. Sphingomyelin synthase 2 deficiency attenuates NFkappaB activation. Arterioscler Thromb Vasc Biol. 2008; 28:1519-26.
Liu J, Zhang H, Li Z, Hailemariam TK, Chakraborty M, Qiu D, Bui HH, Peake DA, Kuo MS, Wadgaonkar R, Cao G, Jiang XC. Sphingomyelin Synthase 2 Is One of the Determinants for Plasma and Liver Sphingomyelin Levels in Mice. Arterioscler Thromb Vasc Biol. 2009; 105:295-303.
Liu J, Huan C, Chakraborty M, Zhang H, Lu D, Kuo M, Cao G, Jiang XC. Macrophage Sphingomyelin Synthase 2 (SMS2) Deficiency Decreases Atherosclerosis in Mice. Circ. Res. 2009; 105(3):295-303.
Li Z, Li Y, Chakraborty M, Fan Y, Bui HH, Peake D.A, Kuo MS, Xiao X, Cao G, Jiang XC. Liver-specific deficiency of serine palmitoyltransferase (SPT) subunit 2 decreases plasma sphingomyelin and apolipoprotein E levels. J. Biol. Chem. 2009; 284(39):27010-9.
Fan Y, Shi F, Liu J, Dong J, Bui HH, Peake DA, Kuo MS, Cao G, Jiang XC. Selective reduction in the sphingomyelin content of atherogenic lipoproteins inhibits their retention in murine aortas and the subsequent development of atherosclerosis. Arterioscler Thromb Vasc Biol. 2010 Nov;30(11):2114-20.
Li Z, Zhang H, Liu J, Liang CP, Li Y, Li Y, Teitelman G, Beyer T, Bui HH, Peake DA, Zhang Y, Sanders PE, Kuo MS, Park TS, Cao G, Jiang XC. Reducing plasma membrane sphingomyelin increases insulin sensitivity. Mol Cell Biol. 2011;31(20):4205-18.
Yazdanyar A, Jiang, XC. Liver specific phospholipid transfer protein (PLTP) expression in PLTP null background promotes VLDL production in mice. Hepatology. 2012, 56:576-84.
Li Z, Ding, T., Pan, X., Li, Y., Li, R., Sanders, P.E., Kuo, M., Hussain, M.M., Cao, G., and Jiang XC. (2012) Lysophosphatidylcholine acyltransferase 3 knockdown-mediated liver lysophosphatidylcholine accumulation promotes very low density lipoprotein production by enhancing microsomal triglyceride transfer protein expression. J. Biol. Chem. 2012; 287:20122-31.
Li Z, Fan, Y., Liu, J., Li, Y., Huan, C., Bui, H.H., Kuo, M., Park, T.S., Cao, G., and Jiang XC. (2012) The effect of Sphingomyelin Synthase 1 Deficiency on Sphingolipid Metabolism and Atherosclerosis in Mice. Arterioscler. Thromb. Vasc. Biol.2012; 32:1577-84.
Chakraborty M, Lou, Huan C, Kuo M, Park T, Cao, G, Jiang XC. Myeloid cell-specific serine palmitoyltransferase subunit 2 haploinsufficiency reduces murine atherosclerosis. J Clin Invest. 2013;123(5):2332-2339.
Yazdanyar A, Quan W, Weijun Jin, Jiang XC. Liver-specific phospholipid transfer protein (PLTP) deficiency reduces high density lipoprotein (HDL) and non-HDL production. Arterioscler Thromb Vasc Biol. 2013;9:2058-64.
Jiang H, Yazdanyar A, Lou B, Chen Y, Zhao X, Li R, Bui H, Kuo MS, Navab M, Qin S, Li Z, Jin W, Jiang XC. Adipocyte Phospholipid Transfer Protein and Lipoprotein Metabolism. Arterioscler Thromb Vasc Biol. 2015;Feb;35(2):316-22.
Li Z, Jiang H, Ding T, Lou C, Bui HH, Kuo MS, Jiang XC. Deficiency in Lysophosphatidylcholine Acyltransferase 3 Reduces Plasma Levels of Lipids by Reducing Lipid Absorption in Mice. Gastroenterology. 2015 Nov;149(6):1519-29.
Kabir I, Li Z, Bui HH, Kuo MS, Gao G, Jiang XC. Small intestine but not liver lysophosphatidylcholine acyltransferase 3 (Lpcat3) deficiency has a dominant effect on plasma lipid metabolism. J Biol Chem. 2016, In press.