Larry L. Swift, Ph.D.

Faculty Appointments
Professor of Pathology, Microbiology and Immunology
Ph.D., Physical Chemistry, Vanderbilt University, Nashville, TennesseeB.S., Chemistry, Indiana Central College, Indianapolis, Indiana
Office Address
CC-3327A MCN
TN 2561
Research Description
Our laboratory has a longstanding interest in the assembly and secretion of very low density lipoproteins (VLDL) by the liver. VLDL transport triglyceride to peripheral tissues for storage and/or utilization and are the sole precursors of plasma low density lipoproteins (LDL), which have been positively correlated with risk for atherosclerotic heart disease. Our studies have focused on the mechanism by which microsomal triglyceride transfer protein (MTP), a lipid transfer protein, adds lipid to the forming lipoprotein within the endoplasmic reticulum and the Golgi complex.

The discovery by our laboratory that MTP is also present in adipose tissue and is associated with the surface of lipid droplets has led to exciting new studies to delineate the role of MTP within adipocytes. Using molecular, cellular, and in vivo approaches, the laboratory is studying how MTP interacts with lipid droplets and how it promotes lipid droplet maturation. The studies could prove important in understanding how fat is stored and in understanding the factors involved in obesity and its many complications, including atherosclerotic heart disease.

Research Keywords
Lipoprotein Assembly, Lipid Droplet Formation, Adipocyte Biology
Berglund ED, Kang L, Lee-Young RS, Hasenour CM, Lustig DG, Lynes SE, Donahue EP, Swift LL, Charron MJ, Wasserman DH. Glucagon and lipid interactions in the regulation of hepatic AMPK signaling and expression of PPARalpha and FGF21 transcripts in vivo. Am. J. Physiol. Endocrinol. Metab [print-electronic]. 2010 Oct; 299(4): E607-14. PMID: 20663988, PMCID: PMC2957865, PII: ajpendo.00263.2010, DOI: 10.1152/ajpendo.00263.2010, ISSN: 1522-1555.

Shearer J, Coenen KR, Pencek RR, Swift LL, Wasserman DH, Rottman JN. Long chain fatty acid uptake in vivo: comparison of [125I]-BMIPP and [3H]-bromopalmitate. Lipids [print-electronic]. 2008 Aug; 43(8): 703-11. PMID: 18481132, DOI: 10.1007/s11745-008-3183-4, ISSN: 0024-4201.

Stafford JM, Yu F, Printz R, Hasty AH, Swift LL, Niswender KD. Central nervous system neuropeptide Y signaling modulates VLDL triglyceride secretion. Diabetes [print-electronic]. 2008 Jun; 57(6): 1482-90. PMID: 18332095, PMCID: PMC3968924, PII: db07-1702, DOI: 10.2337/db07-1702, ISSN: 1939-327X.

Lo CM, Nordskog BK, Nauli AM, Zheng S, Vonlehmden SB, Yang Q, Lee D, Swift LL, Davidson NO, Tso P. Why does the gut choose apolipoprotein B48 but not B100 for chylomicron formation?. Am. J. Physiol. Gastrointest. Liver Physiol [print-electronic]. 2008 Jan; 294(1): G344-52. PMID: 18006607, PII: 00123.2007, DOI: 10.1152/ajpgi.00123.2007, ISSN: 0193-1857.

Mohler PJ, Zhu MY, Blade AM, Ham AJ, Shelness GS, Swift LL. Identification of a novel isoform of microsomal triglyceride transfer protein. J. Biol. Chem [print-electronic]. 2007 Sep 9/14/2007; 282(37): 26981-8. PMID: 17635917, PII: M700500200, DOI: 10.1074/jbc.M700500200, ISSN: 0021-9258.

Buchowski MS, Swift LL, Akohoue SA, Shankar SM, Flakoll PJ, Abumrad N. Defects in postabsorptive plasma homeostasis of fatty acids in sickle cell disease. JPEN J Parenter Enteral Nutr. 2007 Jul; 31(4): 263-8. PMID: 17595432, PMCID: PMC2916689, PII: 31/4/263, ISSN: 0148-6071.

Fan D, Qiu S, Overton CD, Yancey PG, Swift LL, Jerome WG, Linton MF, Fazio S. Impaired secretion of apolipoprotein E2 from macrophages. J. Biol. Chem [print-electronic]. 2007 May 5/4/2007; 282(18): 13746-53. PMID: 17341585, PII: M611754200, DOI: 10.1074/jbc.M611754200, ISSN: 0021-9258.

Dove DE, Su YR, Swift LL, Linton MF, Fazio S. ACAT1 deficiency increases cholesterol synthesis in mouse peritoneal macrophages. Atherosclerosis [print-electronic]. 2006 Jun; 186(2): 267-74. PMID: 16144700, PII: S0021-9150(05)00516-2, DOI: 10.1016/j.atherosclerosis.2005.08.005, ISSN: 0021-9150.

Braun NA, Mohler PJ, Weisgraber KH, Hasty AH, Linton MF, Yancey PG, Su YR, Fazio S, Swift LL. Intracellular trafficking of recycling apolipoprotein E in Chinese hamster ovary cells. J. Lipid Res [print-electronic]. 2006 Jun; 47(6): 1176-86. PMID: 16534141, PII: M500503-JLR200, DOI: 10.1194/jlr.M500503-JLR200, ISSN: 0022-2275.

Zhu MY, Hasty AH, Harris C, Linton MF, Fazio S, Swift LL. Physiological relevance of apolipoprotein E recycling: studies in primary mouse hepatocytes. Metab. Clin. Exp. 2005 Oct; 54(10): 1309-15. PMID: 16154429, PII: S0026-0495(05)00181-2, DOI: 10.1016/j.metabol.2005.04.019, ISSN: 0026-0495.

Hasty AH, Plummer MR, Weisgraber KH, Linton MF, Fazio S, Swift LL. The recycling of apolipoprotein E in macrophages: influence of HDL and apolipoprotein A-I. J. Lipid Res [print-electronic]. 2005 Jul; 46(7): 1433-9. PMID: 15805547, PII: M400418-JLR200, DOI: 10.1194/jlr.M400418-JLR200, ISSN: 0022-2275.

Swift LL, Kakkad B, Boone C, Jovanovska A, Jerome WG, Mohler PJ, Ong DE. Microsomal triglyceride transfer protein expression in adipocytes: a new component in fat metabolism. FEBS Lett. 2005 Jun 6/6/2005; 579(14): 3183-9. PMID: 15922333, PII: S0014-5793(05)00584-3, DOI: 10.1016/j.febslet.2005.05.009, ISSN: 0014-5793.

Swift LL, Jovanovska A, Kakkad B, Ong DE. Microsomal triglyceride transfer protein expression in mouse intestine. Histochem. Cell Biol [print-electronic]. 2005 Jun; 123(4-5): 475-82. PMID: 15891896, DOI: 10.1007/s00418-005-0772-7, ISSN: 0948-6143.

Dove DE, Su YR, Zhang W, Jerome WG, Swift LL, Linton MF, Fazio S. ACAT1 deficiency disrupts cholesterol efflux and alters cellular morphology in macrophages. Arterioscler. Thromb. Vasc. Biol [print-electronic]. 2005 Jan; 25(1): 128-34. PMID: 15499044, PII: 01.ATV.0000148323.94021.e5, DOI: 10.1161/01.ATV.0000148323.94021.e5, ISSN: 1524-4636.

Nobuhiko A, Suganuma E, Babaev VR, Fogo A, Swift LL, Linton MF, Fazio S, Ichikawa I, Kon V. Angiotensin II amplifies macrophage-driven atherosclerosis. Arterioscler. Thromb. Vasc. Biol [print-electronic]. 2004 Nov; 24(11): 2143-8. PMID: 15374850, PII: 01.ATV.0000145607.03879.e0, DOI: 10.1161/01.ATV.0000145607.03879.e0, ISSN: 1524-4636.

Farkas MH, Weisgraber KH, Shepherd VL, Linton MF, Fazio S, Swift LL. The recycling of apolipoprotein E and its amino-terminal 22 kDa fragment: evidence for multiple redundant pathways. J. Lipid Res [print-electronic]. 2004 Aug; 45(8): 1546-54. PMID: 15145976, PII: M400104-JLR200, DOI: 10.1194/jlr.M400104-JLR200, ISSN: 0022-2275.

Ma LJ, Mao SL, Taylor KL, Kanjanabuch T, Guan Y, Zhang Y, Brown NJ, Swift LL, McGuinness OP, Wasserman DH, Vaughan DE, Fogo AB. Prevention of obesity and insulin resistance in mice lacking plasminogen activator inhibitor 1. Diabetes. 2004 Feb; 53(2): 336-46. PMID: 14747283, ISSN: 0012-1797.

Swift LL, Zhu MY, Kakkad B, Jovanovska A, Neely MD, Valyi-Nagy K, Roberts RL, Ong DE, Jerome WG. Subcellular localization of microsomal triglyceride transfer protein. J. Lipid Res [print-electronic]. 2003 Oct; 44(10): 1841-9. PMID: 12837846, PII: M300276-JLR200, DOI: 10.1194/jlr.M300276-JLR200, ISSN: 0022-2275.

Farkas MH, Swift LL, Hasty AH, Linton MF, Fazio S. The recycling of apolipoprotein E in primary cultures of mouse hepatocytes. Evidence for a physiologic connection to high density lipoprotein metabolism. J. Biol. Chem [print-electronic]. 2003 Mar 3/14/2003; 278(11): 9412-7. PMID: 12524433, PII: M208026200, DOI: 10.1074/jbc.M208026200, ISSN: 0021-9258.

Valyi-Nagy K, Harris C, Swift LL. The assembly of hepatic very low density lipoproteins: evidence of a role for the Golgi apparatus. Lipids. 2002 Sep; 37(9): 879-84. PMID: 12458623, ISSN: 0024-4201.

Bassett CN, Swift LL, Montine KS, Markesbery WR, Montine TJ. Cerebrospinal fluid lipoprotein delivery to human neuronal cells is increased in Alzheimer's disease and is dependent on apoE monomer concentration. J. Alzheimers Dis. 2002 Feb; 4(1): 19-30. PMID: 12214015, ISSN: 1387-2877.

Reich EE, Montine KS, Gross MD, Roberts LJ, Swift LL, Morrow JD, Montine TJ. Interactions between apolipoprotein E gene and dietary alpha-tocopherol influence cerebral oxidative damage in aged mice. J. Neurosci. 2001 Aug 8/15/2001; 21(16): 5993-9. PMID: 11487622, PII: 21/16/5993, ISSN: 1529-2401.

Swift LL, Farkas MH, Major AS, Valyi-Nagy K, Linton MF, Fazio S. A recycling pathway for resecretion of internalized apolipoprotein E in liver cells. J. Biol. Chem [print-electronic]. 2001 Jun 6/22/2001; 276(25): 22965-70. PMID: 11304532, PII: M100172200, DOI: 10.1074/jbc.M100172200, ISSN: 0021-9258.

Swift LL, Valyi-Nagy K, Rowland C, Harris C. Assembly of very low density lipoproteins in mouse liver: evidence of heterogeneity of particle density in the Golgi apparatus. J. Lipid Res. 2001 Feb; 42(2): 218-24. PMID: 11181751, ISSN: 0022-2275.

Reich EE, Markesbery WR, Roberts LJ, Swift LL, Morrow JD, Montine TJ. Quantification of F-ring and D-/E-ring isoprostanes and neuroprostanes in Alzheimer's disease. Adv. Exp. Med. Biol. 2001; 500: 253-6. PMID: 11764949, ISSN: 0065-2598.

Fazio S, Major AS, Swift LL, Gleaves LA, Accad M, Linton MF, Farese RV. Increased atherosclerosis in LDL receptor-null mice lacking ACAT1 in macrophages. J. Clin. Invest. 2001 Jan; 107(2): 163-71. PMID: 11160132, PMCID: PMC198874, DOI: 10.1172/JCI10310, ISSN: 0021-9738.

Reich EE, Markesbery WR, Roberts LJ, Swift LL, Morrow JD, Montine TJ. Brain regional quantification of F-ring and D-/E-ring isoprostanes and neuroprostanes in Alzheimer's disease. Am. J. Pathol. 2001 Jan; 158(1): 293-7. PMID: 11141503, PMCID: PMC1850257, PII: S0002-9440(10)63968-5, DOI: 10.1016/S0002-9440(10)63968-5, ISSN: 0002-9440.

Neely MD, Swift LL, Montine TJ. Human, but not bovine, oxidized cerebral spinal fluid lipoproteins disrupt neuronal microtubules. Lipids. 2000 Nov; 35(11): 1249-57. PMID: 11132184, ISSN: 0024-4201.

Bassett CN, Montine KS, Neely MD, Swift LL, Montine TJ. Cerebrospinal fluid lipoproteins in Alzheimer's disease. Microsc. Res. Tech. 2000 Aug 8/15/2000; 50(4): 282-6. PMID: 10936881, PII: 10.1002/1097-0029(20000815)50:4<282::AID-JEMT6>3.0.CO;2-T, DOI: 10.1002/1097-0029(20000815)50:4<282::AID-JEMT6>3.0.CO;2-T, ISSN: 1059-910X.

Fazio S, Linton MF, Swift LL. The cell biology and physiologic relevance of ApoE recycling. Trends Cardiovasc. Med. 2000 Jan; 10(1): 23-30. PMID: 11150725, PII: S1050-1738(00)00033-5, ISSN: 1050-1738.

Bassett CN, Neely MD, Sidell KR, Markesbery WR, Swift LL, Montine TJ. Cerebrospinal fluid lipoproteins are more vulnerable to oxidation in Alzheimer's disease and are neurotoxic when oxidized ex vivo. Lipids. 1999 Dec; 34(12): 1273-80. PMID: 10652986, ISSN: 0024-4201.

Hasty AH, Linton MF, Swift LL, Fazio S. Determination of the lower threshold of apolipoprotein E resulting in remnant lipoprotein clearance. J. Lipid Res. 1999 Aug; 40(8): 1529-38. PMID: 10428991, ISSN: 0022-2275.

Montine TJ, Montine KS, Olson SJ, Graham DG, Roberts LJ, Morrow JD, Linton MF, Fazio S, Swift LL. Increased cerebral cortical lipid peroxidation and abnormal phospholipids in aged homozygous apoE-deficient C57BL/6J mice. Exp. Neurol. 1999 Jul; 158(1): 234-41. PMID: 10448437, PII: S0014-4886(99)97067-X, DOI: 10.1006/exnr.1999.7067, ISSN: 0014-4886.

Fazio S, Linton MF, Hasty AH, Swift LL. Recycling of apolipoprotein E in mouse liver. J. Biol. Chem. 1999 Mar 3/19/1999; 274(12): 8247-53. PMID: 10075730, ISSN: 0021-9258.

Montine KS, Bassett CN, Ou JJ, Markesbery WR, Swift LL, Montine TJ. Apolipoprotein E allelic influence on human cerebrospinal fluid apolipoproteins. J. Lipid Res. 1998 Dec; 39(12): 2443-51. PMID: 9831633, ISSN: 0022-2275.

Morrow JD, Roberts LJ, Daniel VC, Awad JA, Mirochnitchenko O, Swift LL, Burk RF. Comparison of formation of D2/E2-isoprostanes and F2-isoprostanes in vitro and in vivo--effects of oxygen tension and glutathione. Arch. Biochem. Biophys. 1998 May 5/1/1998; 353(1): 160-71. PMID: 9578611, PII: S0003-9861(98)90645-2, DOI: 10.1006/abbi.1998.0645, ISSN: 0003-9861.

Montine TJ, Montine KS, Swift LL. Central nervous system lipoproteins in Alzheimer's disease. Am. J. Pathol. 1997 Dec; 151(6): 1571-5. PMID: 9403708, PMCID: PMC1858368, ISSN: 0002-9440.

Hada T, Swift LL, Brash AR. Discovery of 5R-lipoxygenase activity in oocytes of the surf clam, Spisula solidissima. Biochim. Biophys. Acta. 1997 Jun 6/2/1997; 1346(2): 109-19. PMID: 9219894, PII: S0005-2760(96)00179-8, ISSN: 0006-3002.

Sindelar DK, Chu CA, Rohlie M, Neal DW, Swift LL, Cherrington AD. The role of fatty acids in mediating the effects of peripheral insulin on hepatic glucose production in the conscious dog. Diabetes. 1997 Feb; 46(2): 187-96. PMID: 9000693, ISSN: 0012-1797.

Swift LL. Role of the Golgi apparatus in the phosphorylation of apolipoprotein B. J. Biol. Chem. 1996 Dec 12/6/1996; 271(49): 31491-5. PMID: 8940163, ISSN: 0021-9258.

Swift LL. Assembly of very low density lipoproteins in rat liver: a study of nascent particles recovered from the rough endoplasmic reticulum. J. Lipid Res. 1995 Mar; 36(3): 395-406. PMID: 7775852, ISSN: 0022-2275.

Moore MC, Pagliassotti MJ, Swift LL, Asher J, Murrell J, Neal D, Cherrington AD. Disposition of a mixed meal by the conscious dog. Am. J. Physiol. 1994 Apr; 266(4 Pt 1): E666-75. PMID: 8178989, ISSN: 0002-9513.

Longmire AW, Swift LL, Roberts LJ, Awad JA, Burk RF, Morrow JD. Effect of oxygen tension on the generation of F2-isoprostanes and malondialdehyde in peroxidizing rat liver microsomes. Biochem. Pharmacol. 1994 Mar 3/29/1994; 47(7): 1173-7. PMID: 8161346, ISSN: 0006-2952.

Swift LL, Hill JO, Peters JC, Greene HL. Plasma lipids and lipoproteins during 6 d of maintenance feeding with long-chain, medium-chain, and mixed-chain triglycerides. Am. J. Clin. Nutr. 1992 Nov; 56(5): 881-6. PMID: 1415007, ISSN: 0002-9165.

Awazu M, Yared A, Swift LL, Hoover RL, Ichikawa I. Dietary fatty acid modulates glomerular atrial natriuretic peptide receptor. Kidney Int. 1992 Aug; 42(2): 265-71. PMID: 1328748, ISSN: 0085-2538.

Atkinson JB, Swift LL, Virmani R. Watanabe heritable hyperlipidemic rabbits. Familial hypercholesterolemia. Am. J. Pathol. 1992 Mar; 140(3): 749-53. PMID: 1546748, PMCID: PMC1886168, ISSN: 0002-9440.

Pavlou SN, Brewer K, Farley MG, Lindner J, Bastias MC, Rogers BJ, Swift LL, Rivier JE, Vale WW, Conn PM. Combined administration of a gonadotropin-releasing hormone antagonist and testosterone in men induces reversible azoospermia without loss of libido. J. Clin. Endocrinol. Metab. 1991 Dec; 73(6): 1360-9. PMID: 1955518, DOI: 10.1210/jcem-73-6-1360, ISSN: 0021-972X.

Greene HL, Swift LL, Knapp HR. Hyperlipidemia and fatty acid composition in patients treated for type IA glycogen storage disease. J. Pediatr. 1991 Sep; 119(3): 398-403. PMID: 1880653, ISSN: 0022-3476.

Swift LL, Hill JO, Peters JC, Greene HL. Medium-chain fatty acids: evidence for incorporation into chylomicron triglycerides in humans. Am. J. Clin. Nutr. 1990 Nov; 52(5): 834-6. PMID: 2239759, ISSN: 0002-9165.

Atkinson JB, Swift LL. Nifedipine reduces atherogenesis in cholesterol-fed heterozygous WHHL rabbits. Atherosclerosis. 1990 Oct; 84(2-3): 195-201. PMID: 2282099, PII: 0021-9150(90)90091-V, ISSN: 0021-9150.

Jackowski MM, Swift LL, Cohen S, McKanna JA. Morphologic changes in human carcinoma cells (A-431) stimulated by epidermal growth factor: effect of cholesterol and low-density lipoproteins on the ruffling response. J. Cell. Physiol. 1990 Mar; 142(3): 458-68. PMID: 2312611, DOI: 10.1002/jcp.1041420304, ISSN: 0021-9541.

Hill JO, Peters JC, Swift LL, Yang D, Sharp T, Abumrad N, Greene HL. Changes in blood lipids during six days of overfeeding with medium or long chain triglycerides. J. Lipid Res. 1990 Mar; 31(3): 407-16. PMID: 2187945, ISSN: 0022-2275.

Atkinson JB, Hoover RL, Berry KK, Swift LL. Cholesterol-fed heterozygous Watanabe heritable hyperlipidemic rabbits: a new model for atherosclerosis. Atherosclerosis. 1989 Aug; 78(2-3): 123-36. PMID: 2783197, PII: 0021-9150(89)90216-5, ISSN: 0021-9150.

Harrison JC, Swift LL, LeQuire VS. Identification of lipoprotein-binding proteins in rat liver Golgi apparatus membranes. J. Lipid Res. 1988 Nov; 29(11): 1439-49. PMID: 2853718, ISSN: 0022-2275.

Swift LL, Gray ME, LeQuire VS. Intestinal lipoprotein synthesis in control and hypercholesterolemic rats. Biochim. Biophys. Acta. 1988 Sep 9/23/1988; 962(2): 186-95. PMID: 3167076, ISSN: 0006-3002.