Skip to main content
PMC home page
Protein & Cell logoLink to Protein & Cell
. 2012 Mar 23;3(3):173–181. doi: 10.1007/s13238-012-2025-6

Lipid homeostasis and the formation of macrophage-derived foam cells in atherosclerosis

Yuan Yuan 1, Peng Li 2, Jing Ye 1,✉
PMCID: PMC4875426  PMID: 22447659

Abstract

Atherosclerosis is a chronic, inflammatory disorder characterized by the deposition of excess lipids in the arterial intima. The formation of macrophage-derived foam cells in a plaque is a hallmark of the development of atherosclerosis. Lipid homeostasis, especially cholesterol homeostasis, plays a crucial role during the formation of foam cells. Recently, lipid droplet-associated proteins, including PAT and CIDE family proteins, have been shown to control the development of atherosclerosis by regulating the formation, growth, stabilization and functions of lipid droplets in macrophage-derived foam cells. This review focuses on the potential mechanisms of formation of macrophage-derived foam cells in atherosclerosis with particular emphasis on the role of lipid homeostasis and lipid droplet-associated proteins. Understanding the process of foam cell formation will aid in the future discovery of novel therapeutic interventions for atherosclerosis.

Keywords: macrophage, foam cell, atherosclerosis, cholesterol, lipid droplet-associated proteins

References

  1. Adorni M.P., Zimetti F., Billheimer J.T., Wang N., Rader D.J., Phillips M.C., Rothblat G.H. The roles of different pathways in the release of cholesterol from macrophages. J Lipid Res. 2007;48:2453–2462. doi: 10.1194/jlr.M700274-JLR200. [DOI] [PubMed] [Google Scholar]
  2. An G., Wang H., Tang R., Yago T., McDaniel J.M., McGee S., Huo Y., Xia L. P-selectin glycoprotein ligand-1 is highly expressed on Ly-6Chi monocytes and a major determinant for Ly-6Chi monocyte recruitment to sites of atherosclerosis in mice. Circulation. 2008;117:3227–3237. doi: 10.1161/CIRCULATIONAHA.108.771048. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Ashraf M.Z., Gupta N. Scavenger receptors: Implications in atherothrombotic disorders. Int J Biochem Cell Biol. 2011;43:697–700. doi: 10.1016/j.biocel.2011.01.019. [DOI] [PubMed] [Google Scholar]
  4. Borradaile N.M., Han X., Harp J.D., Gale S.E., Ory D.S., Schaffer J.E. Disruption of endoplasmic reticulum structure and integrity in lipotoxic cell death. J Lipid Res. 2006;47:2726–2737. doi: 10.1194/jlr.M600299-JLR200. [DOI] [PubMed] [Google Scholar]
  5. Brown M.S., Goldstein J.L. The SREBP pathway: regulation of cholesterol metabolism by proteolysis of a membrane-bound transcription factor. Cell. 1997;89:331–340. doi: 10.1016/S0092-8674(00)80213-5. [DOI] [PubMed] [Google Scholar]
  6. Brown M.S., Goldstein J.L. A proteolytic pathway that controls the cholesterol content of membranes, cells, and blood. Proc Natl Acad Sci U S A. 1999;96:11041–11048. doi: 10.1073/pnas.96.20.11041. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Brunham L.R., Singaraja R.R., Duong M., Timmins J.M., Fievet C., Bissada N., Kang M.H., Samra A., Fruchart J.C., McManus B., et al. Tissue-specific roles of ABCA1 influence susceptibility to atherosclerosis. Arterioscler Thromb Vasc Biol. 2009;29:548–554. doi: 10.1161/ATVBAHA.108.182303. [DOI] [PubMed] [Google Scholar]
  8. Buechler C., Ritter M., Duong C.Q., Orso E., Kapinsky M., Schmitz G. Adipophilin is a sensitive marker for lipid loading in human blood monocytes. Biochim Biophys Acta. 2001;1532:97–104. doi: 10.1016/S1388-1981(01)00121-4. [DOI] [PubMed] [Google Scholar]
  9. Buers I., Hofnagel O., Ruebel A., Severs N.J., Robenek H. Lipid droplet associated proteins: an emerging role in atherogenesis. Histol Histopathol. 2011;26:631–642. doi: 10.14670/HH-26.631. [DOI] [PubMed] [Google Scholar]
  10. Buers I., Robenek H., Lorkowski S., Nitschke Y., Severs N.J., Hofnagel O. TIP47, a lipid cargo protein involved in macrophage triglyceride metabolism. Arterioscler Thromb Vasc Biol. 2009;29:767–773. doi: 10.1161/ATVBAHA.108.182675. [DOI] [PubMed] [Google Scholar]
  11. Bultel S., Helin L., Clavey V., Chinetti-Gbaguidi G., Rigamonti E., Colin M., Fruchart J.C., Staels B., Lestavel S. Liver X receptor activation induces the uptake of cholesteryl esters from high density lipoproteins in primary human macrophages. Arterioscler Thromb Vasc Biol. 2008;28:2288–2295. doi: 10.1161/ATVBAHA.108.175042. [DOI] [PubMed] [Google Scholar]
  12. Burgess B., Naus K., Chan J., Hirsch-Reinshagen V., Tansley G., Matzke L., Chan B., Wilkinson A., Fan J., Donkin J., et al. Overexpression of human ABCG1 does not affect atherosclerosis in fat-fed ApoE-deficient mice. Arterioscler Thromb Vasc Biol. 2008;28:1731–1737. doi: 10.1161/ATVBAHA.108.168542. [DOI] [PubMed] [Google Scholar]
  13. Chawla A., Boisvert W.A., Lee C.H., Laffitte B.A., Barak Y., Joseph S.B., Liao D., Nagy L., Edwards P.A., Curtiss L.K., et al. A PPAR gamma-LXR-ABCA1 pathway in macrophages is involved in cholesterol efflux and atherogenesis. Mol Cell. 2001;7:161–171. doi: 10.1016/S1097-2765(01)00164-2. [DOI] [PubMed] [Google Scholar]
  14. Chen F.L., Yang Z.H., Wang X.C., Liu Y., Yang Y.H., Li L.X., Liang W.C., Zhou W.B., Hu R.M. Adipophilin affects the expression of TNF-alpha, MCP-1, and IL-6 in THP-1 macrophages. Mol Cell Biochem. 2010;337:193–199. doi: 10.1007/s11010-009-0299-7. [DOI] [PubMed] [Google Scholar]
  15. Chinetti G., Lestavel S., Bocher V., Remaley A.T., Neve B., Torra I.P., Teissier E., Minnich A., Jaye M., Duverger N., et al. PPAR-alpha and PPAR-gamma activators induce cholesterol removal from human macrophage foam cells through stimulation of the ABCA1 pathway. Nat Med. 2001;7:53–58. doi: 10.1038/83348. [DOI] [PubMed] [Google Scholar]
  16. Chinetti-Gbaguidi G., Rigamonti E., Helin L., Mutka A.L., Lepore M., Fruchart J.C., Clavey V., Ikonen E., Lestavel S., Staels B. Peroxisome proliferator-activated receptor alpha controls cellular cholesterol trafficking in macrophages. J Lipid Res. 2005;46:2717–2725. doi: 10.1194/jlr.M500326-JLR200. [DOI] [PubMed] [Google Scholar]
  17. Combadière C., Potteaux S., Rodero M., Simon T., Pezard A., Esposito B., Merval R., Proudfoot A., Tedgui A., Mallat Z. Combined inhibition of CCL2, CX3CR1, and CCR5 abrogates Ly6C(hi) and Ly6C(lo) monocytosis and almost abolishes atherosclerosis in hypercholesterolemic mice. Circulation. 2008;117:1649–1657. doi: 10.1161/CIRCULATIONAHA.107.745091. [DOI] [PubMed] [Google Scholar]
  18. Duewell P., Kono H., Rayner K.J., Sirois C.M., Vladimer G., Bauernfeind F.G., Abela G.S., Franchi L., Nuñez G., Schnurr M., et al. NLRP3 inflammasomes are required for atherogenesis and activated by cholesterol crystals. Nature. 2010;464:1357–1361. doi: 10.1038/nature08938. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Faber B.C., Cleutjens K.B., Niessen R.L., Aarts P.L., Boon W., Greenberg A.S., Kitslaar P.J., Tordoir J.H., Daemen M.J. Identification of genes potentially involved in rupture of human atherosclerotic plaques. Circ Res. 2001;89:547–554. doi: 10.1161/hh1801.096340. [DOI] [PubMed] [Google Scholar]
  20. Fazio S., Major A.S., Swift L.L., Gleaves L.A., Accad M., Linton M.F., Farese R.V., Jr. Increased atherosclerosis in LDL receptor-null mice lacking ACAT1 in macrophages. J Clin Invest. 2001;107:163–171. doi: 10.1172/JCI10310. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Feingold K.R., Kazemi M.R., Magra A.L., McDonald C.M., Chui L.G., Shigenaga J.K., Patzek S.M., Chan Z.W., Londos C., Grunfeld C. ADRP/ADFP and Mal1 expression are increased in macrophages treated with TLR agonists. Atherosclerosis. 2010;209:81–88. doi: 10.1016/j.atherosclerosis.2009.08.042. [DOI] [PubMed] [Google Scholar]
  22. Ghosh S., St Clair R.W., Rudel L.L. Mobilization of cytoplasmic CE droplets by overexpression of human macrophage cholesteryl ester hydrolase. J Lipid Res. 2003;44:1833–1840. doi: 10.1194/jlr.M300162-JLR200. [DOI] [PubMed] [Google Scholar]
  23. Ghosh S., Zhao B., Bie J., Song J. Macrophage cholesteryl ester mobilization and atherosclerosis. Vascul Pharmacol. 2010;52:1–10. doi: 10.1016/j.vph.2009.10.002. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Glass C.K., Witztum J.L. Atherosclerosis. the road ahead. Cell. 2001;104:503–516. doi: 10.1016/S0092-8674(01)00238-0. [DOI] [PubMed] [Google Scholar]
  25. Goldstein J.L., DeBose-Boyd R.A., Brown M.S. Protein sensors for membrane sterols. Cell. 2006;124:35–46. doi: 10.1016/j.cell.2005.12.022. [DOI] [PubMed] [Google Scholar]
  26. Gong J., Sun Z., Li P. CIDE proteins and metabolic disorders. Curr Opin Lipidol. 2009;20:121–126. doi: 10.1097/MOL.0b013e328328d0bb. [DOI] [PubMed] [Google Scholar]
  27. Gordon S., Martinez F.O. Alternative activation of macrophages: mechanism and functions. Immunity. 2010;32:593–604. doi: 10.1016/j.immuni.2010.05.007. [DOI] [PubMed] [Google Scholar]
  28. Gu J.Q., Wang D.F., Yan X.G., Zhong W.L., Zhang J., Fan B., Ikuyama S. A Toll-like receptor 9-mediated pathway stimulates perilipin 3 (TIP47) expression and induces lipid accumulation in macrophages. Am J Physiol Endocrinol Metab. 2010;299:E593–E600. doi: 10.1152/ajpendo.00159.2010. [DOI] [PubMed] [Google Scholar]
  29. Hofnagel O., Buers I., Schnoor M., Lorkowski S., Robenek H. Expression of perilipin isoforms in cell types involved in atherogenesis. Atherosclerosis. 2007;190:14–15. doi: 10.1016/j.atherosclerosis.2006.06.010. [DOI] [PubMed] [Google Scholar]
  30. Im S.S., Yousef L., Blaschitz C., Liu J.Z., Edwards R.A., Young S.G., Raffatellu M., Osborne T.F. Linking lipid metabolism to the innate immune response in macrophages through sterol regulatory element binding protein-1a. Cell Metab. 2011;13:540–549. doi: 10.1016/j.cmet.2011.04.001. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Kadl A., Meher A.K., Sharma P.R., Lee M.Y., Doran A.C., Johnstone S.R., Elliott M.R., Gruber F., Han J., Chen W., et al. Identification of a novel macrophage phenotype that develops in response to atherogenic phospholipids via Nrf2. Circ Res. 2010;107:737–746. doi: 10.1161/CIRCRESAHA.109.215715. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. Kunjathoor V.V., Febbraio M., Podrez E.A., Moore K.J., Andersson L., Koehn S., Rhee J.S., Silverstein R., Hoff H.F., Freeman M.W. Scavenger receptors class A-I/II and CD36 are the principal receptors responsible for the uptake of modified low density lipoprotein leading to lipid loading in macrophages. J Biol Chem. 2002;277:49982–49988. doi: 10.1074/jbc.M209649200. [DOI] [PubMed] [Google Scholar]
  33. Langlois D., Forcheron F., Li J.Y., del Carmine P., Neggazi S., Beylot M. Increased atherosclerosis in mice deficient in perilipin1. Lipids Health Dis. 2011;10:169. doi: 10.1186/1476-511X-10-169. [DOI] [PMC free article] [PubMed] [Google Scholar]
  34. Larigauderie G., Cuaz-Pérolin C., Younes A.B., Furman C., Lasselin C., Copin C., Jaye M., Fruchart J.C., Rouis M. Adipophilin increases triglyceride storage in human macrophages by stimulation of biosynthesis and inhibition of beta-oxidation. FEBS J. 2006;273:3498–3510. doi: 10.1111/j.1742-4658.2006.05357.x. [DOI] [PubMed] [Google Scholar]
  35. Larigauderie G., Furman C., Jaye M., Lasselin C., Copin C., Fruchart J.C., Castro G., Rouis M. Adipophilin enhances lipid accumulation and prevents lipid efflux from THP-1 macrophages: potential role in atherogenesis. Arterioscler Thromb Vasc Biol. 2004;24:504–510. doi: 10.1161/01.ATV.0000115638.27381.97. [DOI] [PubMed] [Google Scholar]
  36. Lee C.H., Chawla A., Urbiztondo N., Liao D., Boisvert W.A., Evans R.M., Curtiss L.K. Transcriptional repression of atherogenic inflammation: modulation by PPARdelta. Science. 2003;302:453–457. doi: 10.1126/science.1087344. [DOI] [PubMed] [Google Scholar]
  37. Lee K.J., Kim H.A., Kim P.H., Lee H.S., Ma K.R., Park J.H., Kim D.J., Hahn J.H. Ox-LDL suppresses PMA-induced MMP-9 expression and activity through CD36-mediated activation of PPAR-g. Exp Mol Med. 2004;36:534–544. doi: 10.1038/emm.2004.68. [DOI] [PubMed] [Google Scholar]
  38. Li A.C., Binder C.J., Gutierrez A., Brown K.K., Plotkin C.R., Pattison J.W., Valledor A.F., Davis R.A., Willson T.M., Witztum J.L., et al. Differential inhibition of macrophage foam-cell formation and atherosclerosis in mice by PPARalpha, beta/delta, and gamma. J Clin Invest. 2004;114:1564–1576. doi: 10.1172/JCI18730. [DOI] [PMC free article] [PubMed] [Google Scholar]
  39. Li H., Song Y., Li F., Zhang L., Gu Y., Zhang L., Jiang L., Dong W., Ye J., Li Q. Identification of lipid droplet-associated proteins in the formation of macrophage-derived foam cells using microarrays. Int J Mol Med. 2010;26:231–239. doi: 10.3892/ijmm_00000457. [DOI] [PubMed] [Google Scholar]
  40. Li J.Z., Li P. Cide proteins and the development of obesity. Novartis Found Symp. 2007;286:155–159. doi: 10.1002/9780470985571.ch13. [DOI] [PubMed] [Google Scholar]
  41. Li J.Z., Ye J., Xue B., Qi J., Zhang J., Zhou Z., Li Q., Wen Z., Li P. Cideb regulates diet-induced obesity, liver steatosis, and insulin sensitivity by controlling lipogenesis and fatty acid oxidation. Diabetes. 2007;56:2523–2532. doi: 10.2337/db07-0040. [DOI] [PubMed] [Google Scholar]
  42. Listenberger L.L., Ostermeyer-Fay A.G., Goldberg E.B., Brown W.J., Brown D.A. Adipocyte differentiation-related protein reduces the lipid droplet association of adipose triglyceride lipase and slows triacylglycerol turnover. J Lipid Res. 2007;48:2751–2761. doi: 10.1194/jlr.M700359-JLR200. [DOI] [PubMed] [Google Scholar]
  43. Makowski L., Boord J.B., Maeda K., Babaev V.R., Uysal K.T., Morgan M.A., Parker R.A., Suttles J., Fazio S., Hotamisligil G.S., et al. Lack of macrophage fatty-acid-binding protein aP2 protects mice deficient in apolipoprotein E against atherosclerosis. Nat Med. 2001;7:699–705. doi: 10.1038/89076. [DOI] [PMC free article] [PubMed] [Google Scholar]
  44. Manning-Tobin J.J., Moore K.J., Seimon T.A., Bell S.A., Sharuk M., Alvarez-Leite J.I., de Winther M.P., Tabas I., Freeman M.W. Loss of SR-A and CD36 activity reduces atherosclerotic lesion complexity without abrogating foam cell formation in hyperlipidemic mice. Arterioscler Thromb Vasc Biol. 2009;29:19–26. doi: 10.1161/ATVBAHA.108.176644. [DOI] [PMC free article] [PubMed] [Google Scholar]
  45. Martinez F.O., Gordon S., Locati M., Mantovani A. Transcriptional profiling of the human monocyte-to-macrophage differentiation and polarization: new molecules and patterns of gene expression. J Immunol. 2006;177:7303–7311. doi: 10.4049/jimmunol.177.10.7303. [DOI] [PubMed] [Google Scholar]
  46. Moon Y.A., Shah N.A., Mohapatra S., Warrington J.A., Horton J.D. Identification of a mammalian long chain fatty acyl elongase regulated by sterol regulatory element-binding proteins. J Biol Chem. 2001;276:45358–45366. doi: 10.1074/jbc.M108413200. [DOI] [PubMed] [Google Scholar]
  47. Moore K.J., Kunjathoor V.V., Koehn S.L., Manning J.J., Tseng A.A., Silver J.M., McKee M., Freeman M.W. Loss of receptor-mediated lipid uptake via scavenger receptor A or CD36 pathways does not ameliorate atherosclerosis in hyperlipidemic mice. J Clin Invest. 2005;115:2192–2201. doi: 10.1172/JCI24061. [DOI] [PMC free article] [PubMed] [Google Scholar]
  48. Nishino N., Tamori Y., Tateya S., Kawaguchi T., Shibakusa T., Mizunoya W., Inoue K., Kitazawa R., Kitazawa S., Matsuki Y., et al. FSP27 contributes to efficient energy storage in murine white adipocytes by promoting the formation of unilocular lipid droplets. J Clin Invest. 2008;118:2808–2821. doi: 10.1172/JCI34090. [DOI] [PMC free article] [PubMed] [Google Scholar]
  49. Ouimet M., Franklin V., Mak E., Liao X., Tabas I., Marcel Y.L. Autophagy regulates cholesterol efflux from macrophage foam cells via lysosomal acid lipase. Cell Metab. 2011;13:655–667. doi: 10.1016/j.cmet.2011.03.023. [DOI] [PMC free article] [PubMed] [Google Scholar]
  50. Paul A., Chan L., Bickel P.E. The PAT family of lipid droplet proteins in heart and vascular cells. Curr Hypertens Rep. 2008;10:461–466. doi: 10.1007/s11906-008-0086-y. [DOI] [PMC free article] [PubMed] [Google Scholar]
  51. Paul A., Chang B.H., Li L., Yechoor V.K., Chan L. Deficiency of adipose differentiation-related protein impairs foam cell formation and protects against atherosclerosis. Circ Res. 2008;102:1492–1501. doi: 10.1161/CIRCRESAHA.107.168070. [DOI] [PMC free article] [PubMed] [Google Scholar]
  52. Pello O.M., Silvestre C., De Pizzol M., Andrés V. A glimpse on the phenomenon of macrophage polarization during atherosclerosis. Immunobiology. 2011;216:1172–1176. doi: 10.1016/j.imbio.2011.05.010. [DOI] [PubMed] [Google Scholar]
  53. Perrey S., Legendre C., Matsuura A., Guffroy C., Binet J., Ohbayashi S., Tanaka T., Ortuno J.C., Matsukura T., Laugel T., et al. Preferential pharmacological inhibition of macrophage ACAT increases plaque formation in mouse and rabbit models of atherogenesis. Atherosclerosis. 2001;155:359–370. doi: 10.1016/S0021-9150(00)00599-2. [DOI] [PubMed] [Google Scholar]
  54. Podrez E.A., Febbraio M., Sheibani N., Schmitt D., Silverstein R.L., Hajjar D.P., Cohen P.A., Frazier W.A., Hoff H.F., Hazen S.L. Macrophage scavenger receptor CD36 is the major receptor for LDL modified by monocyte-generated reactive nitrogen species. J Clin Invest. 2000;105:1095–1108. doi: 10.1172/JCI8574. [DOI] [PMC free article] [PubMed] [Google Scholar]
  55. Posokhova E.N., Khoshchenko O.M., Chasovskikh M.I., Pivovarova E.N., Dushkin M.I. Lipid synthesis in macrophages during inflammation in vivo: effect of agonists of peroxisome proliferator activated receptors alpha and gamma and of retinoid X receptors. Biochemistry (Mosc) 2008;73:296–304. doi: 10.1134/S0006297908030097. [DOI] [PubMed] [Google Scholar]
  56. Puri V., Konda S., Ranjit S., Aouadi M., Chawla A., Chouinard M., Chakladar A., Czech M.P. Fat-specific protein 27, a novel lipid droplet protein that enhances triglyceride storage. J Biol Chem. 2007;282:34213–34218. doi: 10.1074/jbc.M707404200. [DOI] [PubMed] [Google Scholar]
  57. Puri V., Ranjit S., Konda S., Nicoloro S.M., Straubhaar J., Chawla A., Chouinard M., Lin C., Burkart A., Corvera S., et al. Cidea is associated with lipid droplets and insulin sensitivity in humans. Proc Natl Acad Sci U S A. 2008;105:7833–7838. doi: 10.1073/pnas.0802063105. [DOI] [PMC free article] [PubMed] [Google Scholar]
  58. Rader D.J., Puré E. Lipoproteins, macrophage function, and atherosclerosis: beyond the foam cell? Cell Metab. 2005;1:223–230. doi: 10.1016/j.cmet.2005.03.005. [DOI] [PubMed] [Google Scholar]
  59. Rios F.J., Gidlund M., Jancar S. Pivotal role for platelet-activating factor receptor in CD36 expression and oxLDL uptake by human monocytes/macrophages. Cell Physiol Biochem. 2011;27:363–372. doi: 10.1159/000327962. [DOI] [PubMed] [Google Scholar]
  60. Robenek H., Lorkowski S., Schnoor M., Troyer D. Spatial integration of TIP47 and adipophilin in macrophage lipid bodies. J Biol Chem. 2005;280:5789–5794. doi: 10.1074/jbc.M407194200. [DOI] [PubMed] [Google Scholar]
  61. Robenek H., Robenek M.J., Troyer D. PAT family proteins pervade lipid droplet cores. J Lipid Res. 2005;46:1331–1338. doi: 10.1194/jlr.M400323-JLR200. [DOI] [PubMed] [Google Scholar]
  62. Siegel-Axel D., Daub K., Seizer P., Lindemann S., Gawaz M. Platelet lipoprotein interplay: trigger of foam cell formation and driver of atherosclerosis. Cardiovasc Res. 2008;78:8–17. doi: 10.1093/cvr/cvn015. [DOI] [PubMed] [Google Scholar]
  63. Takahashi K., Takeya M., Sakashita N. Multifunctional roles of macrophages in the development and progression of atherosclerosis in humans and experimental animals. Med Electron Microsc. 2002;35:179–203. doi: 10.1007/s007950200023. [DOI] [PubMed] [Google Scholar]
  64. Taketa K., Matsumura T., Yano M., Ishii N., Senokuchi T., Motoshima H., Murata Y., Kim-Mitsuyama S., Kawada T., Itabe H., et al. Oxidized low density lipoprotein activates peroxisome proliferator-activated receptor-alpha (PPARalpha) and PPARgamma through MAPK-dependent COX-2 expression in macrophages. J Biol Chem. 2008;283:9852–9862. doi: 10.1074/jbc.M703318200. [DOI] [PubMed] [Google Scholar]
  65. Tansey J.T., Sztalryd C., Gruia-Gray J., Roush D.L., Zee J.V., Gavrilova O., Reitman M.L., Deng C.X., Li C., Kimmel A.R., et al. Perilipin ablation results in a lean mouse with aberrant adipocyte lipolysis, enhanced leptin production, and resistance to diet-induced obesity. Proc Natl Acad Sci U S A. 2001;98:6494–6499. doi: 10.1073/pnas.101042998. [DOI] [PMC free article] [PubMed] [Google Scholar]
  66. Tobias P., Curtiss L.K. Thematic review series: The immune system and atherogenesis. Paying the price for pathogen protection: toll receptors in atherogenesis. J Lipid Res. 2005;46:404–411. doi: 10.1194/jlr.R400015-JLR200. [DOI] [PubMed] [Google Scholar]
  67. Toh S.Y., Gong J., Du G., Li J.Z., Yang S., Ye J., Yao H., Zhang Y., Xue B., Li Q., et al. Up-regulation of mitochondrial activity and acquirement of brown adipose tissue-like property in the white adipose tissue of fsp27 deficient mice. PLoS One. 2008;3:e2890. doi: 10.1371/journal.pone.0002890. [DOI] [PMC free article] [PubMed] [Google Scholar]
  68. Tordjman K., Bernal-Mizrachi C., Zemany L., Weng S., Feng C., Zhang F., Leone T.C., Coleman T., Kelly D.P., Semenkovich C.F. PPARalpha deficiency reduces insulin resistance and atherosclerosis in apoE-null mice. J Clin Invest. 2001;107:1025–1034. doi: 10.1172/JCI11497. [DOI] [PMC free article] [PubMed] [Google Scholar]
  69. Trigatti B., Rayburn H., Viñals M., Braun A., Miettinen H., Penman M., Hertz M., Schrenzel M., Amigo L., Rigotti A., et al. Influence of the high density lipoprotein receptor SR-BI on reproductive and cardiovascular pathophysiology. Proc Natl Acad Sci U S A. 1999;96:9322–9327. doi: 10.1073/pnas.96.16.9322. [DOI] [PMC free article] [PubMed] [Google Scholar]
  70. Ye J., Li J.Z., Liu Y., Li X., Yang T., Ma X., Li Q., Yao Z., Li P. Cideb, an ER- and lipid droplet-associated protein, mediates VLDL lipidation and maturation by interacting with apolipoprotein B. Cell Metab. 2009;9:177–190. doi: 10.1016/j.cmet.2008.12.013. [DOI] [PubMed] [Google Scholar]
  71. Yvan-Charvet L., Ranalletta M., Wang N., Han S., Terasaka N., Li R., Welch C., Tall A.R. Combined deficiency of ABCA1 and ABCG1 promotes foam cell accumulation and accelerates atherosclerosis in mice. J Clin Invest. 2007;117:3900–3908. doi: 10.1172/JCI33372. [DOI] [PMC free article] [PubMed] [Google Scholar]
  72. Zhao B., Song J., Chow W.N., St Clair R.W., Rudel L.L., Ghosh S. Macrophage-specific transgenic expression of cholesteryl ester hydrolase significantly reduces atherosclerosis and lesion necrosis in Ldlr mice. J Clin Invest. 2007;117:2983–2992. doi: 10.1172/JCI30485. [DOI] [PMC free article] [PubMed] [Google Scholar]
  73. Zhao Y., Pennings M., Vrins C.L., Calpe-Berdiel L., Hoekstra M., Kruijt J.K., Ottenhoff R., Hildebrand R.B., van der Sluis R., Jessup W., et al. Hypocholesterolemia, foam cell accumulation, but no atherosclerosis in mice lacking ABC-transporter A1 and scavenger receptor BI. Atherosclerosis. 2011;218:314–322. doi: 10.1016/j.atherosclerosis.2011.07.096. [DOI] [PubMed] [Google Scholar]
  74. Zhou X., He W., Huang Z., Gotto A.M., Jr, Hajjar D.P., Han J. Genetic deletion of low density lipoprotein receptor impairs sterol-induced mouse macrophage ABCA1 expression. A new SREBP1-dependent mechanism. J Biol Chem. 2008;283:2129–2138. doi: 10.1074/jbc.M706636200. [DOI] [PubMed] [Google Scholar]

Articles from Protein & Cell are provided here courtesy of Oxford University Press

RESOURCES