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Janet Sparks

TitleProfessor
InstitutionSchool of Medicine and Dentistry
DepartmentPathology and Laboratory Medicine
AddressUniversity of Rochester Medical Center
School of Medicine and Dentistry
601 Elmwood Ave, Bpx 626
Rochester NY 14642
 
 Overview
Plasma lipoproteins are the major vehicles for non-aqueous transport of lipids, including cholesterol and triglyceride, and lipid-soluble vitamins such as vitamin A and E, from the liver and intestine to tissues. Derangements in lipoprotein metabolism are involved in progression of atherosclerosis, an underlying cause of heart disease and strokes which remain the major cause of death in the United States. Insulin, known as a key regulator in carbohydrate metabolism, plays a major regulatory role in hepatic lipoprotein metabolism. Insulin acts by inhibition of secretion of triglyceride-rich lipoproteins through a mechanism involving the stimulation of the intracellular degradation of apolipoprotein B, an essential structural apolipoprotein. Research in my laboratory links specific events involved in insulin receptor (IR) signal transduction with microsomal events that lead to degradation of apo B. The focus is on insulin-activated phosphatidylinositide 3-kinase (PI-3-kinase) in the translocation of apo B and its intracellular transport within the secretory pathway. Investigations employ primary rat hepatocytes, McArdle RH-7777 rat hepatoma cells and HepG2 cells and assay of IR signaling, Beta-subunit phosphorylation, IRS phosphorylation, PI 3-K activation and of PI 3-K mass in subcellular fractions. Progress will allow better understanding of insulin regulation of triglyceride-rich lipoprotein secretion by liver and will provide insights into the mechanisms involved in the development of hypertriglyceridemia in human obesity and insulin resistance syndromes such as metabolic Syndrome X which increase the risk of atherosclerosis complications up to ten times.

 
 Selected Publications
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  1. Sparks CE, Corsetti JP, Sparks JD. High-density lipoproteins: taking the good with the bad. Curr Opin Lipidol. 2014 Jun; 25(3):230-2.
    View in: PubMed
  2. Huang CK, Pang H, Wang L, Niu Y, Luo J, Chang E, Sparks JD, Lee SO, Chang C. New Therapy via Targeting Androgen Receptor in Monocytes/Macrophages to Battle Atherosclerosis. Hypertension. 2014 Jun; 63(6):1345-53.
    View in: PubMed
  3. Greene MW, Burrington CM, Lynch DT, Davenport SK, Johnson AK, Horsman MJ, Chowdhry S, Zhang J, Sparks JD, Tirrell PC. Lipid Metabolism, Oxidative Stress and Cell Death Are Regulated by PKC Delta in a Dietary Model of Nonalcoholic Steatohepatitis. PLoS One. 2014 Jan 15; 9(1):e85848.
    View in: PubMed
  4. Sparks CE, Sparks JD. Hepatic postprandial transition and very low-density lipoprotein biogenesis. Curr Opin Lipidol. 2013 Oct; 24(5):450-2.
    View in: PubMed
  5. Sparks JD, O'Dell C, Chamberlain JM, Sparks CE. Insulin-dependent apolipoprotein B degradation is mediated by autophagy and involves class I and class III phosphatidylinositide 3-kinases. Biochem Biophys Res Commun. 2013 Jun 14; 435(4):616-20.
    View in: PubMed
  6. Chamberlain JM, O'Dell C, Sparks CE, Sparks JD. Insulin suppression of apolipoprotein B in McArdle RH7777 cells involves increased sortilin 1 interaction and lysosomal targeting. Biochem Biophys Res Commun. 2013 Jan 4; 430(1):66-71.
    View in: PubMed
  7. Yu IC, Lin HY, Liu NC, Sparks JD, Yeh S, Fang LY, Chen L, Chang C. Neuronal Androgen Receptor Regulates Insulin Sensitivity via Suppression of Hypothalamic NF-?B-Mediated PTP1B Expression. Diabetes. 2013 Feb; 62(2):411-23.
    View in: PubMed
  8. Sparks CE, Sparks JD. Hepatic steatosis and VLDL hypersecretion. Curr Opin Lipidol. 2012 Aug; 23(4):395-7.
    View in: PubMed
  9. Sparks JD, Sparks CE, Adeli K. Selective hepatic insulin resistance, VLDL overproduction, and hypertriglyceridemia. Arterioscler Thromb Vasc Biol. 2012 Sep; 32(9):2104-12.
    View in: PubMed
  10. Kim E, Liu NC, Yu IC, Lin HY, Lee YF, Sparks JD, Chen LM, Chang C. Metformin inhibits nuclear receptor TR4-mediated hepatic stearoyl-CoA desaturase 1 gene expression with altered insulin sensitivity. Diabetes. 2011 May; 60(5):1493-503.
    View in: PubMed
  11. Sparks JD, Chamberlain JM, O'Dell C, Khatun I, Hussain MM, Sparks CE. Acute suppression of apo B secretion by insulin occurs independently of MTP. Biochem Biophys Res Commun. 2011 Mar 11; 406(2):252-6.
    View in: PubMed
  12. Nigro P, Satoh K, O'Dell MR, Soe NN, Cui Z, Mohan A, Abe J, Alexis JD, Sparks JD, Berk BC. Cyclophilin A is an inflammatory mediator that promotes atherosclerosis in apolipoprotein E-deficient mice. J Exp Med. 2011 Jan 17; 208(1):53-66.
    View in: PubMed
  13. Meex SJ, Andreo U, Sparks JD, Fisher EA. Huh-7 or HepG2 cells: which is the better model for studying human apolipoprotein-B100 assembly and secretion? J Lipid Res. 2011 Jan; 52(1):152-8.
    View in: PubMed
  14. Sparks JD, Cianci J, Jokinen J, Chen LS, Sparks CE. Interleukin-6 mediates hepatic hypersecretion of apolipoprotein B. Am J Physiol Gastrointest Liver Physiol. 2010 Oct; 299(4):G980-9.
    View in: PubMed
  15. Galloway CA, Ashton J, Sparks JD, Mooney RA, Smith HC. Metabolic regulation of APOBEC-1 complementation factor trafficking in mouse models of obesity and its positive correlation with the expression of ApoB protein in hepatocytes. Biochim Biophys Acta. 2010 Nov; 1802(11):976-85.
    View in: PubMed
  16. Sparks CE, Sparks JD. Lipid metabolism: insights into the complexity of VLDL metabolic pathways. Curr Opin Lipidol. 2010 Jun; 21(3):280-1.
    View in: PubMed
  17. Uc EY, Rizzo M, Anderson SW, Dastrup E, Sparks JD, Dawson JD. Driving under low-contrast visibility conditions in Parkinson disease. Neurology. 2009 Oct 6; 73(14):1103-10.
    View in: PubMed
  18. Caviglia JM, Sparks JD, Toraskar N, Brinker AM, Yin TC, Dixon JL, Brasaemle DL. ABHD5/CGI-58 facilitates the assembly and secretion of apolipoprotein B lipoproteins by McA RH7777 rat hepatoma cells. Biochim Biophys Acta. 2009 Mar; 1791(3):198-205.
    View in: PubMed
  19. Sparks JD, Sparks CE. Overindulgence and metabolic syndrome: is FoxO1 a missing link? J Clin Invest. 2008 Jun; 118(6):2012-5.
    View in: PubMed
  20. Lin HY, Yu IC, Wang RS, Chen YT, Liu NC, Altuwaijri S, Hsu CL, Ma WL, Jokinen J, Sparks JD, Yeh S, Chang C. Increased hepatic steatosis and insulin resistance in mice lacking hepatic androgen receptor. Hepatology. 2008 Jun; 47(6):1924-35.
    View in: PubMed
  21. Yu IC, Lin HY, Liu NC, Wang RS, Sparks JD, Yeh S, Chang C. Hyperleptinemia without obesity in male mice lacking androgen receptor in adipose tissue. Endocrinology. 2008 May; 149(5):2361-8.
    View in: PubMed
  22. Liu NC, Lin WJ, Kim E, Collins LL, Lin HY, Yu IC, Sparks JD, Chen LM, Lee YF, Chang C. Loss of TR4 orphan nuclear receptor reduces phosphoenolpyruvate carboxykinase-mediated gluconeogenesis. Diabetes. 2007 Dec; 56(12):2901-9.
    View in: PubMed
  23. Uc EY, Rizzo M, Anderson SW, Sparks JD, Rodnitzky RL, Dawson JD. Driving with distraction in Parkinson disease. Neurology. 2006 Nov 28; 67(10):1774-80.
    View in: PubMed
  24. Nieman KM, Hartz CS, Szegedi SS, Garrow TA, Sparks JD, Schalinske KL. Folate status modulates the induction of hepatic glycine N-methyltransferase and homocysteine metabolism in diabetic rats. Am J Physiol Endocrinol Metab. 2006 Dec; 291(6):E1235-42.
    View in: PubMed
  25. Chirieac DV, Davidson NO, Sparks CE, Sparks JD. PI3-kinase activity modulates apo B available for hepatic VLDL production in apobec-1-/- mice. Am J Physiol Gastrointest Liver Physiol. 2006 Sep; 291(3):G382-8.
    View in: PubMed
  26. Sparks JD, Collins HL, Chirieac DV, Cianci J, Jokinen J, Sowden MP, Galloway CA, Sparks CE. Hepatic very-low-density lipoprotein and apolipoprotein B production are increased following in vivo induction of betaine-homocysteine S-methyltransferase. Biochem J. 2006 Apr 15; 395(2):363-71.
    View in: PubMed
  27. Lin HY, Xu Q, Yeh S, Wang RS, Sparks JD, Chang C. Insulin and leptin resistance with hyperleptinemia in mice lacking androgen receptor. Diabetes. 2005 Jun; 54(6):1717-25.
    View in: PubMed
  28. Chirieac DV, Collins HL, Cianci J, Sparks JD, Sparks CE. Altered triglyceride-rich lipoprotein production in Zucker diabetic fatty rats. Am J Physiol Endocrinol Metab. 2004 Jul; 287(1):E42-9.
    View in: PubMed
  29. Au CS, Wagner A, Chong T, Qiu W, Sparks JD, Adeli K. Insulin regulates hepatic apolipoprotein B production independent of the mass or activity of Akt1/PKBalpha. Metabolism. 2004 Feb; 53(2):228-35.
    View in: PubMed
  30. Patel NA, Apostolatos HS, Mebert K, Chalfant CE, Watson JE, Pillay TS, Sparks J, Cooper DR. Insulin regulates protein kinase CbetaII alternative splicing in multiple target tissues: development of a hormonally responsive heterologous minigene. Mol Endocrinol. 2004 Apr; 18(4):899-911.
    View in: PubMed
  31. Chirieac DV, Cianci J, Collins HL, Sparks JD, Sparks CE. Insulin suppression of VLDL apo B secretion is not mediated by the LDL receptor. Biochem Biophys Res Commun. 2002 Sep 13; 297(1):134-7.
    View in: PubMed
  32. Fisher EA, Pan M, Chen X, Wu X, Wang H, Jamil H, Sparks JD, Williams KJ. The triple threat to nascent apolipoprotein B. Evidence for multiple, distinct degradative pathways. J Biol Chem. 2001 Jul 27; 276(30):27855-63.
    View in: PubMed
  33. Chirieac DV, Chirieac LR, Corsetti JP, Cianci J, Sparks CE, Sparks JD. Glucose-stimulated insulin secretion suppresses hepatic triglyceride-rich lipoprotein and apoB production. Am J Physiol Endocrinol Metab. 2000 Nov; 279(5):E1003-11.
    View in: PubMed
  34. Sparks JD, Shaw WN, Corsetti JP, Bolognino M, Pesek JF, Sparks CE. Insulin-treated Zucker diabetic fatty rats retain the hypertriglyceridemia associated with obesity. Metabolism. 2000 Nov; 49(11):1424-30.
    View in: PubMed
  35. Collins HL, Sparks CE, Sparks JD. B48 is preferentially translated over B100 in cells with increased endogenous apo B mRNA. Biochem Biophys Res Commun. 2000 Jul 14; 273(3):1156-60.
    View in: PubMed
  36. Corsetti JP, Sparks JD, Peterson RG, Smith RL, Sparks CE. Effect of dietary fat on the development of non-insulin dependent diabetes mellitus in obese Zucker diabetic fatty male and female rats. Atherosclerosis. 2000 Feb; 148(2):231-41.
    View in: PubMed
  37. Sowden MP, Collins HL, Smith HC, Garrow TA, Sparks JD, Sparks CE. Apolipoprotein B mRNA and lipoprotein secretion are increased in McArdle RH-7777 cells by expression of betaine-homocysteine S-methyltransferase. Biochem J. 1999 Aug 1; 341 ( Pt 3):639-45.
    View in: PubMed
  38. Van Mater D, Sowden MP, Cianci J, Sparks JD, Sparks CE, Ballatori N, Smith HC. Ethanol increases apolipoprotein B mRNA editing in rat primary hepatocytes and McArdle cells. Biochem Biophys Res Commun. 1998 Nov 18; 252(2):334-9.
    View in: PubMed
  39. Sparks JD, Phung TL, Bolognino M, Cianci J, Khurana R, Peterson RG, Sowden MP, Corsetti JP, Sparks CE. Lipoprotein alterations in 10- and 20-week-old Zucker diabetic fatty rats: hyperinsulinemic versus insulinopenic hyperglycemia. Metabolism. 1998 Nov; 47(11):1315-24.
    View in: PubMed
  40. Phung TL, Roncone A, Jensen KL, Sparks CE, Sparks JD. Phosphoinositide 3-kinase activity is necessary for insulin-dependent inhibition of apolipoprotein B secretion by rat hepatocytes and localizes to the endoplasmic reticulum. J Biol Chem. 1997 Dec 5; 272(49):30693-702.
    View in: PubMed
  41. Phung TL, Mooney RA, Kulas DT, Sparks CE, Sparks JD. Suppression of the protein tyrosine phosphatase LAR reduces apolipoprotein B secretion by McA-RH7777 rat hepatoma cells. Biochem Biophys Res Commun. 1997 Aug 18; 237(2):367-71.
    View in: PubMed
  42. Sparks JD, Collins HL, Sabio I, Sowden MP, Smith HC, Cianci J, Sparks CE. Effects of fatty acids on apolipoprotein B secretion by McArdle RH-7777 rat hepatoma cells. Biochim Biophys Acta. 1997 Jul 12; 1347(1):51-61.
    View in: PubMed
  43. Phung TL, Sowden MP, Sparks JD, Sparks CE, Smith HC. Regulation of hepatic apolipoprotein B RNA editing in the genetically obese Zucker rat. Metabolism. 1996 Sep; 45(9):1056-8.
    View in: PubMed
  44. Schock D, Kuo SR, Steinburg MF, Bolognino M, Sparks JD, Sparks CE, Smith HC. An auxiliary factor containing a 240-kDa protein complex is involved in apolipoprotein B RNA editing. Proc Natl Acad Sci U S A. 1996 Feb 6; 93(3):1097-102.
    View in: PubMed
  45. Sparks JD, Phung TL, Bolognino M, Sparks CE. Insulin-mediated inhibition of apolipoprotein B secretion requires an intracellular trafficking event and phosphatidylinositol 3-kinase activation: studies with brefeldin A and wortmannin in primary cultures of rat hepatocytes. Biochem J. 1996 Jan 15; 313 ( Pt 2):567-74.
    View in: PubMed
  46. Sparks JD, Sparks CE. Chromatographic method for isolation and quantification of apolipoproteins B-100 and B-48. Methods Enzymol. 1996; 263:104-20.
    View in: PubMed
  47. Sparks JD, Sparks CE. Obese Zucker (fa/fa) rats are resistant to insulin's inhibitory effect on hepatic apo B secretion. Biochem Biophys Res Commun. 1994 Nov 30; 205(1):417-22.
    View in: PubMed
  48. Sparks JD, Sparks CE. Insulin regulation of triacylglycerol-rich lipoprotein synthesis and secretion. Biochim Biophys Acta. 1994 Nov 17; 1215(1-2):9-32.
    View in: PubMed
  49. Sparks JD, Corsetti JP, Sparks CE. Liver regrowth and apolipoprotein B secretion by rat hepatocytes following partial hepatectomy. Metabolism. 1994 Jun; 43(6):681-90.
    View in: PubMed
  50. Björnsson OG, Sparks JD, Sparks CE, Gibbons GF. Regulation of VLDL secretion in primary culture of rat hepatocytes: involvement of cAMP and cAMP-dependent protein kinases. Eur J Clin Invest. 1994 Feb; 24(2):137-48.
    View in: PubMed
  51. Chen X, Sparks JD, Yao Z, Fisher EA. Hepatic polysomes that contain apoprotein B mRNA have unusual physical properties. J Biol Chem. 1993 Oct 5; 268(28):21007-13.
    View in: PubMed
  52. Harris SG, Sabio I, Mayer E, Steinberg MF, Backus JW, Sparks JD, Sparks CE, Smith HC. Extract-specific heterogeneity in high-order complexes containing apolipoprotein B mRNA editing activity and RNA-binding proteins. J Biol Chem. 1993 Apr 5; 268(10):7382-92.
    View in: PubMed
  53. Corsetti JP, Sparks JD, Sikora B, Sparks CE. Cellular heterogeneity in binding and uptake of low-density lipoprotein in primary rat hepatocytes. Hepatology. 1993 Apr; 17(4):645-50.
    View in: PubMed
  54. Gibbons GF, Bartlett SM, Sparks CE, Sparks JD. Extracellular fatty acids are not utilized directly for the synthesis of very-low-density lipoprotein in primary cultures of rat hepatocytes. Biochem J. 1992 Nov 1; 287 ( Pt 3):749-53.
    View in: PubMed
  55. Björnsson OG, Sparks JD, Sparks CE, Gibbons GF. Prostaglandins suppress VLDL secretion in primary rat hepatocyte cultures: relationships to hepatic calcium metabolism. J Lipid Res. 1992 Jul; 33(7):1017-27.
    View in: PubMed
  56. Corsetti JP, Way BA, Sparks CE, Sparks JD. Immunolocalization, quantitation and cellular heterogeneity of apolipoprotein B in rat hepatocytes. Hepatology. 1992 Jun; 15(6):1117-24.
    View in: PubMed
  57. Sparks JD, Zolfaghari R, Sparks CE, Smith HC, Fisher EA. Impaired hepatic apolipoprotein B and E translation in streptozotocin diabetic rats. J Clin Invest. 1992 May; 89(5):1418-30.
    View in: PubMed
  58. Björnsson OG, Duerden JM, Bartlett SM, Sparks JD, Sparks CE, Gibbons GF. The role of pancreatic hormones in the regulation of lipid storage, oxidation and secretion in primary cultures of rat hepatocytes. Short- and long-term effects. Biochem J. 1992 Jan 15; 281 ( Pt 2):381-6.
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  59. Corsetti JP, Sterry JA, Sparks JD, Sparks CE, Weintraub M. Effect of weight loss on serum lipoprotein(a) concentrations in an obese population. Clin Chem. 1991 Jul; 37(7):1191-5.
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  60. Smith HC, Kuo SR, Backus JW, Harris SG, Sparks CE, Sparks JD. In vitro apolipoprotein B mRNA editing: identification of a 27S editing complex. Proc Natl Acad Sci U S A. 1991 Feb 15; 88(4):1489-93.
    View in: PubMed
  61. Backus JW, Eagleton MJ, Harris SG, Sparks CE, Sparks JD, Smith HC. Quantitation of endogenous liver apolipoprotein B mRNA editing. Biochem Biophys Res Commun. 1990 Jul 31; 170(2):513-8.
    View in: PubMed
  62. Sparks JD, Sparks CE. Insulin modulation of hepatic synthesis and secretion of apolipoprotein B by rat hepatocytes. J Biol Chem. 1990 May 25; 265(15):8854-62.
    View in: PubMed
  63. Kwong TC, Sparks JD, Pryce DJ, Cianci JF, Sparks CE. Inhibition of apolipoprotein B net synthesis and secretion from cultured rat hepatocytes by the calcium-channel blocker diltiazem. Biochem J. 1989 Oct 15; 263(2):411-5.
    View in: PubMed
  64. Sparks JD, Sparks CE, Miller LL. Insulin effects on apolipoprotein B production by normal, diabetic and treated-diabetic rat liver and cultured rat hepatocytes. Biochem J. 1989 Jul 1; 261(1):83-8.
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  65. Jackson TK, Salhanick AI, Sparks JD, Sparks CE, Bolognino M, Amatruda JM. Insulin-mimetic effects of vanadate in primary cultures of rat hepatocytes. Diabetes. 1988 Sep; 37(9):1234-40.
    View in: PubMed
  66. Sparks JD, Sparks CE, Bolognino M, Roncone AM, Jackson TK, Amatruda JM. Effects of nonketotic streptozotocin diabetes on apolipoprotein B synthesis and secretion by primary cultures of rat hepatocytes. J Clin Invest. 1988 Jul; 82(1):37-43.
    View in: PubMed
  67. Sparks JD, Sparks CE, Roncone AM, Amatruda JM. Secretion of high and low molecular weight phosphorylated apolipoprotein B by hepatocytes from control and diabetic rats. Phosphorylation of APO BH and APO BL. J Biol Chem. 1988 Apr 15; 263(11):5001-4.
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  68. Sparks CE, Sparks JD, Bolognino M, Salhanick A, Strumph PS, Amatruda JM. Insulin effects on apolipoprotein B lipoprotein synthesis and secretion by primary cultures of rat hepatocytes. Metabolism. 1986 Dec; 35(12):1128-36.
    View in: PubMed
  69. Sparks JD, Bolognino M, Trax PA, Sparks CE. The production and utility of monoclonal antibodies to rat apolipoprotein B lipoproteins. Atherosclerosis. 1986 Sep; 61(3):205-11.
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  70. Sparks JD, Sparks CE, Kritchevsky D. Hypercholesterolemia and aortic glycosaminoglycans of rabbits fed semi-purified diets containing sucrose and lactose. Atherosclerosis. 1986 May; 60(2):183-96.
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  71. Kwong TC, Sparks JD, Sparks CE. Lipoprotein and protein binding of the calcium channel blocker diltiazem. Proc Soc Exp Biol Med. 1985 Feb; 178(2):313-6.
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  72. Sparks JD, Sparks CE. Apolipoprotein B and lipoprotein metabolism. Adv Lipid Res. 1985; 21:1-46.
    View in: PubMed

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