Skip to main content
SpringerLink
Log in

Beneficial impact of L-carnitine in liver: a study in a rat model of syndrome X

  • Published:
Amino Acids Aims and scope Submit manuscript

Summary.

The present study was designed to explore whether L-carnitine (CA) regulates insulin signaling and modulates the changes in liver in a well-characterized insulin resistant rat model. Adult male Wistar rats were divided into 4 groups. Groups I and IV animals received starch-based control diet, while groups II and III rats were fed a high fructose-diet (60 g/100 g). Groups III and IV animals additionally received CA (300 mg/kg/day i.p). After a period of 60 days hepatic tyrosine phosphorylation status was determined by assaying protein tyrosine phosphatase (PTP) and protein tyrosine kinase (PTK) activities. Oxidative damage was monitored by immunohistochemical localization of 4-hydroxynonenal (4-HNE), 3-nitrotyrosine (3-NT) and dinitrophenol (DNP)-protein adducts. In addition protein kinase C βII (PKC βII) expression, propidium iodide staining of isolated hepatocytes and histology of liver tissue were determined to examine liver integrity. Fructose-fed rats displayed reduced insulin action, increased expression of PKC βII, altered histology, fragmentation of hepatocyte nuclear DNA, and accumulation of oxidatively modified proteins. Simultaneous treatment with CA alleviated the abnormalities associated with fructose feeding. In summary the data suggest that elevated oxidative damage and PKC expression could in part induce insulin resistance and CA has beneficial impact on liver during insulin resistance with modulatory effects at the post-receptor level.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  • M Artwohl M Roden W Waldhausl A Freudenthaler SM Baumgartner-Parzer (2004) ArticleTitleFree fatty acids trigger apoptosis and inhibit cell cycle progression in human vascular endothelial cells FASEB J 18 146–148 Occurrence Handle14597560 Occurrence Handle1:CAS:528:DC%2BD2cXlvFOktg%3D%3D

    PubMed  CAS  Google Scholar 

  • B Bassienmaier L Mosthab H Mischak A Ullrich HU Haring (1997) ArticleTitleProtein kinase C isoform beta-1 and beta-2 inhibit the tyrosine kinase activity of the insulin receptor Diabetologia 40 863–866 Occurrence Handle10.1007/s001250050761

    Article  Google Scholar 

  • RM Bezerra M Ueno MS Silva DQ Tavares CR Carvalho MJ Saad (2000) ArticleTitleA high fructose diet affects the early steps of insulin action in muscle and liver of rats J Nutr 130 1531–1535 Occurrence Handle10827205 Occurrence Handle1:CAS:528:DC%2BD3cXjsl2htbc%3D

    PubMed  CAS  Google Scholar 

  • TL Broderick HA Quinney GD Lopaschuk (1992) ArticleTitleCarnitine stimulation of glucose oxidation in the fatty acid perfused isolated working rat heart J Biol Chem 267 3758–3763 Occurrence Handle1740427 Occurrence Handle1:CAS:528:DyaK38XhsVyru74%3D

    PubMed  CAS  Google Scholar 

  • CR Carvalho SL Brenelli AC Silva AL Nunes LA Velloso MJ Saad (1996) ArticleTitleEffect of aging on insulin receptor, insulin receptor substrate-1, and phosphatidylinositol 3-kinase in liver and muscle of rats Endocrinology 137 151–159 Occurrence Handle8536607 Occurrence Handle10.1210/en.137.1.151 Occurrence Handle1:CAS:528:DyaK28XhsVOktA%3D%3D

    Article  PubMed  CAS  Google Scholar 

  • C Catena G Giacchetti M Novello G Colussi A Cavarape LA Sechi (2003) ArticleTitleCellular mechanisms of insulin resistance in rats with fructose-induced hypertension Am J Hypertens 16 973–978 Occurrence Handle14573337 Occurrence Handle10.1016/S0895-7061(03)01002-1 Occurrence Handle1:CAS:528:DC%2BD3sXot1Omtro%3D

    Article  PubMed  CAS  Google Scholar 

  • H Chen SJ Wertheimer CH Lin SL Katz KE Amrein P Burn MJ Quon (1997) ArticleTitleProtein-tyrosine phosphatases PTP1B and syp are modulators of insulin-stimulated translocation of GLUT4 in transfected rat adipose cells J Biol Chem 272 8026–8031 Occurrence Handle9065475 Occurrence Handle10.1074/jbc.272.12.8026 Occurrence Handle1:CAS:528:DyaK2sXitFWluro%3D

    Article  PubMed  CAS  Google Scholar 

  • JE Chin M Dickens JM Tavare RA Roth (1992) ArticleTitleOverexpression of protein kinase C isoenzymes alpha, beta I, gamma, and epsilon in cells overexpressing the insulin receptor. Effects on receptor phosphorylation and signaling J Biol Chem 268 6338–6347

    Google Scholar 

  • R Donnelly MJ Reed S Azhar GM Reaven (1994) ArticleTitleExpression of the major isoenzyme of protein kinase-C in skeletal muscle, nPKC theta, varies with muscle type and in response to fructose-induced insulin resistance Endocrinology 135 2369–2374 Occurrence Handle7988419 Occurrence Handle10.1210/en.135.6.2369 Occurrence Handle1:CAS:528:DyaK2MXisFWqsbc%3D

    Article  PubMed  CAS  Google Scholar 

  • EB Fauman MA Saper (1996) ArticleTitleStructure and function of the protein tyrosine phosphatases Trends Biochem Sci 21 413–417 Occurrence Handle8987394 Occurrence Handle10.1016/S0968-0004(96)10059-1 Occurrence Handle1:CAS:528:DyaK28Xntlaqsrc%3D

    Article  PubMed  CAS  Google Scholar 

  • P Faure E Rossini JL Lafond MJ Richard A Favier S Halimi (1997) ArticleTitleVitamin E improves the free radical defense system potential and insulin sensitivity of rats fed high fructose diets J Nutr 127 103–107 Occurrence Handle9040552 Occurrence Handle1:CAS:528:DyaK2sXhtFKrtL8%3D

    PubMed  CAS  Google Scholar 

  • T Furuno T Kanno K Arita M Asami T Utsumi Y Doi M Inoue K Utsumi (2001) ArticleTitleRoles of long chain fatty acids and carnitine in mitochondrial membrane permeability transition Biochem Pharmacol 62 1037–1046 Occurrence Handle11597572 Occurrence Handle10.1016/S0006-2952(01)00745-6 Occurrence Handle1:CAS:528:DC%2BD3MXntlyjsb4%3D

    Article  PubMed  CAS  Google Scholar 

  • M Gschwendt W Kittstein F Marks (1991) ArticleTitleProtein kinase C activation by phorbol esters: do cysteine-rich regions and pseudosubstrate motifs play a role? Trends Biochem Sci 16 167–169 Occurrence Handle1820763 Occurrence Handle10.1016/0968-0004(91)90064-3 Occurrence Handle1:CAS:528:DyaK3MXks1Ogtrk%3D

    Article  PubMed  CAS  Google Scholar 

  • I Gulcin (2006) ArticleTitleAntioxidant and antiradical activities of L-carnitine Life Sci 78 803–811 Occurrence Handle16253281 Occurrence Handle10.1016/j.lfs.2005.05.103 Occurrence Handle1:CAS:528:DC%2BD28XjvVynuw%3D%3D

    Article  PubMed  CAS  Google Scholar 

  • H Ischiropoulos (1998) ArticleTitleBiological tyrosine nitration: a pathophysiological function of nitric oxide and reactive oxygen species Arch Biochem Biophys 356 1–11 Occurrence Handle9681984 Occurrence Handle10.1006/abbi.1998.0755 Occurrence Handle1:STN:280:DyaK1czkvVeqsg%3D%3D

    Article  PubMed  CAS  Google Scholar 

  • N Ishii Z Ogawa K Suzuki K Numakami T Saruta H Itoh (1996) ArticleTitleGlucose loading induces DNA fragmentation in rat proximal tubular cells Metabolism 45 1348–1353 Occurrence Handle8931638 Occurrence Handle10.1016/S0026-0495(96)90114-6 Occurrence Handle1:CAS:528:DyaK28XntVGjtr0%3D

    Article  PubMed  CAS  Google Scholar 

  • GL Kelley G Allan S Azhar (2004) ArticleTitleHigh dietary fructose induces a hepatic stress response resulting in cholesterol and lipid dysregulation Endocrinology 145 548–555 Occurrence Handle14576175 Occurrence Handle10.1210/en.2003-1167 Occurrence Handle1:CAS:528:DC%2BD2cXovFSgsg%3D%3D

    Article  PubMed  CAS  Google Scholar 

  • OH Lowry NJ Rosebrough AL Farr RJ Randall (1951) ArticleTitleProtein measurement with the Folin’s – phenol reagent J Biol Chem 193 265–275 Occurrence Handle14907713 Occurrence Handle1:CAS:528:DyaG38XhsVyrsw%3D%3D

    PubMed  CAS  Google Scholar 

  • DR Mathews JP Hosker AS Rudenkl BA Naylor DF Treacher RC Turner (1985) ArticleTitleHomeostasis model assessment: insulin resistance and β-cells function from fasting plasma glucose and insulin concentrations in man Diabetologia 28 412–419 Occurrence Handle10.1007/BF00280883

    Article  Google Scholar 

  • JP McClung CA Roneker W Mu DJ Lisk P Langlais F Liu XG Lei (2004) ArticleTitleDevelopment of insulin resistance and obesity in mice over expressing cellular glutathione peroxidase Proc Natl Acad Sci USA 101 8852–8857 Occurrence Handle15184668 Occurrence Handle10.1073/pnas.0308096101 Occurrence Handle1:CAS:528:DC%2BD2cXltlWru70%3D

    Article  PubMed  CAS  Google Scholar 

  • I Miwa N Ichimura M Sugiura Y Hamada S Taniguchi (2000) ArticleTitleInhibition of glucose-induced insulin secretion by 4-hydroxy-2-nonenal and other lipid peroxidation products Endocrinology 141 2767–2772 Occurrence Handle10919261 Occurrence Handle10.1210/en.141.8.2767 Occurrence Handle1:CAS:528:DC%2BD3cXnt1Cms74%3D

    Article  PubMed  CAS  Google Scholar 

  • I Mothe OE Van (1996) ArticleTitlePhosphorylation of insulin receptor substrate-1 on multiple serine residues, 612, 632, 662, and 731, modulates insulin action J Biol Chem 271 11222–11227 Occurrence Handle8626671 Occurrence Handle10.1074/jbc.271.19.11222 Occurrence Handle1:CAS:528:DyaK28XivV2is7o%3D

    Article  PubMed  CAS  Google Scholar 

  • AS Mueller MJ Pallauf (2006) ArticleTitleCompendium of the antidiabetic effects of supranutritional selenate doses. In vivo and in vitro investigations with type II diabetic db/db mice J Nutr Biochem 17 548–560 Occurrence Handle16443359 Occurrence Handle10.1016/j.jnutbio.2005.10.006 Occurrence Handle1:CAS:528:DC%2BD28XntlCqsr4%3D

    Article  PubMed  CAS  Google Scholar 

  • MC Mutomba H Yuan M Konyavko S Adachi CB Yokoyama V Esser JD McGarry BM Babior RA Gottlieb (2000) ArticleTitleRegulation of the activity of caspases by L-carnitine and palmitoylcarnitine FEBS Lett 478 19–25 Occurrence Handle10922462 Occurrence Handle10.1016/S0014-5793(00)01817-2 Occurrence Handle1:CAS:528:DC%2BD3cXltVGrsLk%3D

    Article  PubMed  CAS  Google Scholar 

  • P Rajasekar S Kaviarasan CV Anuradha (2005) ArticleTitleL-Carnitine administration prevents oxidative stress in high fructose-fed insulin resistant rats Diabetol Croat 34 21–28

    Google Scholar 

  • U Rauen B Polzar H Stephan HG Mannherz GH de (1999) ArticleTitleCold-induced apoptosis in cultured hepatocytes and liver endothelial cells: mediation by reactive oxygen species FASEB J 13 155–168 Occurrence Handle9872940 Occurrence Handle1:CAS:528:DyaK1MXlt1ynug%3D%3D

    PubMed  CAS  Google Scholar 

  • V Ravichandran DL Esposito J Chen MJ Quon (2001) ArticleTitleProtein kinase C-zeta phosphorylates insulin receptor substrate-1 and impairs its ability to activate phosphatidylinositol 3-kinase in response to insulin J Biol Chem 276 3543–3549 Occurrence Handle11063744 Occurrence Handle10.1074/jbc.M007231200 Occurrence Handle1:CAS:528:DC%2BD3MXhtFWisLo%3D

    Article  PubMed  CAS  Google Scholar 

  • GM Reaven (1994) ArticleTitleSyndrome X: 6 years later J Int Med 736 13–22 Occurrence Handle1:STN:280:ByqD2sjmtlU%3D

    CAS  Google Scholar 

  • PO Seglen (1976) ArticleTitlePreparation of isolated rat liver cells Methods Cell Biol 13 29 Occurrence Handle177845 Occurrence Handle10.1016/S0091-679X(08)61797-5 Occurrence Handle1:CAS:528:DyaE28XkslCgtbY%3D

    Article  PubMed  CAS  Google Scholar 

  • RK Studer PA Craven FR DeRubertis (1997) ArticleTitleAntioxidant inhibition of protein kinase C-signaled increases in transforming growth factor-beta in mesangial cells Metabolism 46 918–925 Occurrence Handle9258275 Occurrence Handle10.1016/S0026-0495(97)90080-9 Occurrence Handle1:CAS:528:DyaK2sXltlSkurw%3D

    Article  PubMed  CAS  Google Scholar 

  • C Szabo (2003) ArticleTitleMultiple pathways of peroxynitrite cytotoxicity Toxicol Lett 140–141 105–112 Occurrence Handle12676456 Occurrence Handle10.1016/S0378-4274(02)00507-6 Occurrence Handle1:CAS:528:DC%2BD3sXisV2htrw%3D

    Article  PubMed  CAS  Google Scholar 

  • C Taghibiglou F Rashid-Kolvear SC Van Iderstine H Le-Tien IG Fantus GF Lewis K Adeli (2002) ArticleTitleHepatic very low density lipoprotein-ApoB overproduction is associated with attenuated hepatic insulin signaling and overexpression of protein tyrosine phosphatase 1B in a fructose-fed hamster model of insulin resistance J Biol Chem 277 793–803 Occurrence Handle11598116 Occurrence Handle10.1074/jbc.M106737200 Occurrence Handle1:CAS:528:DC%2BD38XjslGksQ%3D%3D

    Article  PubMed  CAS  Google Scholar 

  • K Uchida (2003) ArticleTitle4-Hydroxy-2-nonenal: a product and mediator of oxidative stress Progr Lipid Res 42 318–343 Occurrence Handle10.1016/S0163-7827(03)00014-6 Occurrence Handle1:CAS:528:DC%2BD3sXis1yqtro%3D

    Article  CAS  Google Scholar 

  • M Ueno RM Bezerra MS Silva DQ Tavares CR Carvalho MJ Saad (2000) ArticleTitleA high-fructose diet induces changes in pp185 phosphorylation in muscle and liver of rats Braz J Med Biol Res 33 1421–1427 Occurrence Handle11105093 Occurrence Handle10.1590/S0100-879X2000001200004 Occurrence Handle1:CAS:528:DC%2BD3MXkvFKjtQ%3D%3D

    Article  PubMed  CAS  Google Scholar 

  • Q Zeidan M Strauss N Porras G Anselmi (2002) ArticleTitleDifferential long-term subcellular responses in heart and liver to adriamycin stress. Exogenous L-carnitine in cardiac and hepatic protection J Submicrosc Cytol Pathol 34 315–321 Occurrence Handle12408365 Occurrence Handle1:STN:280:DC%2BD38nkvVKkug%3D%3D

    PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Biochemistry and Biotechnology, Faculty of Science, Annamalai University, Annamalai Nagar, Tamil Nadu, India

    P. Rajasekar & C. V. Anuradha

  2. Department of Pathology, Rajah Muthiah Medical College, Annamalai University, Annamalai Nagar, Tamil Nadu, India

    P. Viswanathan

Authors
  1. P. Rajasekar
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. P. Viswanathan
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. C. V. Anuradha
    View author publications

    You can also search for this author in PubMed Google Scholar

Additional information

Authors’ address: Prof. Dr. C. V. Anuradha, Department of Biochemistry and Biotechnology, Annamalai University, Annamalai Nagar 608 002, Tamil Nadu, India

Rights and permissions

Reprints and permissions

About this article

Cite this article

Rajasekar, P., Viswanathan, P. & Anuradha, C. Beneficial impact of L-carnitine in liver: a study in a rat model of syndrome X. Amino Acids 35, 475–483 (2008). https://doi.org/10.1007/s00726-007-0559-3

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00726-007-0559-3

Search

Navigation