Skip to main content
Journal of the Royal Society of Medicine logoLink to Journal of the Royal Society of Medicine
. 2002;95(Suppl 42):33–38.

Correction of dysfunctional fatty acid metabolism using peroxisome proliferator activated receptor gamma agonists.

Nicholas D Oakes 1, Bengt Ljung 1, Germán Camejo 1
PMCID: PMC1308943  PMID: 12216325

Full Text

The Full Text of this article is available as a PDF (510.9 KB).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. ALTSCHUL R., HOFFER A., STEPHEN J. D. Influence of nicotinic acid on serum cholesterol in man. Arch Biochem Biophys. 1955 Feb;54(2):558–559. doi: 10.1016/0003-9861(55)90070-9. [DOI] [PubMed] [Google Scholar]
  2. Basu A., Basu R., Shah P., Vella A., Rizza R. A., Jensen M. D. Systemic and regional free fatty acid metabolism in type 2 diabetes. Am J Physiol Endocrinol Metab. 2001 Jun;280(6):E1000–E1006. doi: 10.1152/ajpendo.2001.280.6.E1000. [DOI] [PubMed] [Google Scholar]
  3. Cha B. S., Ciaraldi T. P., Carter L., Nikoulina S. E., Mudaliar S., Mukherjee R., Paterniti J. R., Jr, Henry R. R. Peroxisome proliferator-activated receptor (PPAR) gamma and retinoid X receptor (RXR) agonists have complementary effects on glucose and lipid metabolism in human skeletal muscle. Diabetologia. 2001 Apr;44(4):444–452. doi: 10.1007/s001250051642. [DOI] [PubMed] [Google Scholar]
  4. Chiu H. C., Kovacs A., Ford D. A., Hsu F. F., Garcia R., Herrero P., Saffitz J. E., Schaffer J. E. A novel mouse model of lipotoxic cardiomyopathy. J Clin Invest. 2001 Apr;107(7):813–822. doi: 10.1172/JCI10947. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Ellis B. A., Poynten A., Lowy A. J., Furler S. M., Chisholm D. J., Kraegen E. W., Cooney G. J. Long-chain acyl-CoA esters as indicators of lipid metabolism and insulin sensitivity in rat and human muscle. Am J Physiol Endocrinol Metab. 2000 Sep;279(3):E554–E560. doi: 10.1152/ajpendo.2000.279.3.E554. [DOI] [PubMed] [Google Scholar]
  6. Fajas L., Debril M. B., Auwerx J. Peroxisome proliferator-activated receptor-gamma: from adipogenesis to carcinogenesis. J Mol Endocrinol. 2001 Aug;27(1):1–9. doi: 10.1677/jme.0.0270001. [DOI] [PubMed] [Google Scholar]
  7. Fruchart J. C., Duriez P., Staels B. Peroxisome proliferator-activated receptor-alpha activators regulate genes governing lipoprotein metabolism, vascular inflammation and atherosclerosis. Curr Opin Lipidol. 1999 Jun;10(3):245–257. doi: 10.1097/00041433-199906000-00007. [DOI] [PubMed] [Google Scholar]
  8. Guertl B., Noehammer C., Hoefler G. Metabolic cardiomyopathies. Int J Exp Pathol. 2000 Dec;81(6):349–372. doi: 10.1046/j.1365-2613.2000.00186.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Ide T., Nakazawa T., Mochizuki T., Murakami K. Tissue-specific actions of antidiabetic thiazolidinediones on the reduced fatty acid oxidation in skeletal muscle and liver of Zucker diabetic fatty rats. Metabolism. 2000 Apr;49(4):521–525. doi: 10.1016/s0026-0495(00)80019-0. [DOI] [PubMed] [Google Scholar]
  10. James O., Day C. Non-alcoholic steatohepatitis: another disease of affluence. Lancet. 1999 May 15;353(9165):1634–1636. doi: 10.1016/S0140-6736(99)00163-4. [DOI] [PubMed] [Google Scholar]
  11. Kelley D. E., Simoneau J. A. Impaired free fatty acid utilization by skeletal muscle in non-insulin-dependent diabetes mellitus. J Clin Invest. 1994 Dec;94(6):2349–2356. doi: 10.1172/JCI117600. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Krssak M., Falk Petersen K., Dresner A., DiPietro L., Vogel S. M., Rothman D. L., Roden M., Shulman G. I. Intramyocellular lipid concentrations are correlated with insulin sensitivity in humans: a 1H NMR spectroscopy study. Diabetologia. 1999 Jan;42(1):113–116. doi: 10.1007/s001250051123. [DOI] [PubMed] [Google Scholar]
  13. Linton M. F., Fazio S. Re-emergence of fibrates in the management of dyslipidemia and cardiovascular risk. Curr Atheroscler Rep. 2000 Jan;2(1):29–35. doi: 10.1007/s11883-000-0092-2. [DOI] [PubMed] [Google Scholar]
  14. Litwin S. E., Raya T. E., Gay R. G., Bedotto J. B., Bahl J. J., Anderson P. G., Goldman S., Bressler R. Chronic inhibition of fatty acid oxidation: new model of diastolic dysfunction. Am J Physiol. 1990 Jan;258(1 Pt 2):H51–H56. doi: 10.1152/ajpheart.1990.258.1.H51. [DOI] [PubMed] [Google Scholar]
  15. Marchesini G., Brizi M., Bianchi G., Tomassetti S., Bugianesi E., Lenzi M., McCullough A. J., Natale S., Forlani G., Melchionda N. Nonalcoholic fatty liver disease: a feature of the metabolic syndrome. Diabetes. 2001 Aug;50(8):1844–1850. doi: 10.2337/diabetes.50.8.1844. [DOI] [PubMed] [Google Scholar]
  16. Martin G., Schoonjans K., Lefebvre A. M., Staels B., Auwerx J. Coordinate regulation of the expression of the fatty acid transport protein and acyl-CoA synthetase genes by PPARalpha and PPARgamma activators. J Biol Chem. 1997 Nov 7;272(45):28210–28217. doi: 10.1074/jbc.272.45.28210. [DOI] [PubMed] [Google Scholar]
  17. McGarry J. D., Dobbins R. L. Fatty acids, lipotoxicity and insulin secretion. Diabetologia. 1999 Feb;42(2):128–138. doi: 10.1007/s001250051130. [DOI] [PubMed] [Google Scholar]
  18. Millar J. S., Packard C. J. Heterogeneity of apolipoprotein B-100-containing lipoproteins: what we have learnt from kinetic studies. Curr Opin Lipidol. 1998 Jun;9(3):197–202. doi: 10.1097/00041433-199806000-00003. [DOI] [PubMed] [Google Scholar]
  19. Motojima K., Passilly P., Peters J. M., Gonzalez F. J., Latruffe N. Expression of putative fatty acid transporter genes are regulated by peroxisome proliferator-activated receptor alpha and gamma activators in a tissue- and inducer-specific manner. J Biol Chem. 1998 Jul 3;273(27):16710–16714. doi: 10.1074/jbc.273.27.16710. [DOI] [PubMed] [Google Scholar]
  20. Oakes N. D., Thalén P. G., Jacinto S. M., Ljung B. Thiazolidinediones increase plasma-adipose tissue FFA exchange capacity and enhance insulin-mediated control of systemic FFA availability. Diabetes. 2001 May;50(5):1158–1165. doi: 10.2337/diabetes.50.5.1158. [DOI] [PubMed] [Google Scholar]
  21. Olsson U., Egnell A. C., Lee M. R., Lundén G. O., Lorentzon M., Salmivirta M., Bondjers G., Camejo G. Changes in matrix proteoglycans induced by insulin and fatty acids in hepatic cells may contribute to dyslipidemia of insulin resistance. Diabetes. 2001 Sep;50(9):2126–2132. doi: 10.2337/diabetes.50.9.2126. [DOI] [PubMed] [Google Scholar]
  22. Otway S., Robinson D. S. The use of a non-ionic detergent (Triton WR 1339) to determine rates of triglyceride entry into the circulation of the rat under different physiological conditions. J Physiol. 1967 May;190(2):321–332. doi: 10.1113/jphysiol.1967.sp008211. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Pan D. A., Lillioja S., Kriketos A. D., Milner M. R., Baur L. A., Bogardus C., Jenkins A. B., Storlien L. H. Skeletal muscle triglyceride levels are inversely related to insulin action. Diabetes. 1997 Jun;46(6):983–988. doi: 10.2337/diab.46.6.983. [DOI] [PubMed] [Google Scholar]
  24. Phillips M. S., Liu Q., Hammond H. A., Dugan V., Hey P. J., Caskey C. J., Hess J. F. Leptin receptor missense mutation in the fatty Zucker rat. Nat Genet. 1996 May;13(1):18–19. doi: 10.1038/ng0596-18. [DOI] [PubMed] [Google Scholar]
  25. Pihlajamäki J., Karjalainen L., Karhapä P., Vauhkonen I., Laakso M. Impaired free fatty acid suppression during hyperinsulinemia is a characteristic finding in familial combined hyperlipidemia, but insulin resistance is observed only in hypertriglyceridemic patients. Arterioscler Thromb Vasc Biol. 2000 Jan;20(1):164–170. doi: 10.1161/01.atv.20.1.164. [DOI] [PubMed] [Google Scholar]
  26. RANDLE P. J., GARLAND P. B., HALES C. N., NEWSHOLME E. A. The glucose fatty-acid cycle. Its role in insulin sensitivity and the metabolic disturbances of diabetes mellitus. Lancet. 1963 Apr 13;1(7285):785–789. doi: 10.1016/s0140-6736(63)91500-9. [DOI] [PubMed] [Google Scholar]
  27. Randle P. J. Regulatory interactions between lipids and carbohydrates: the glucose fatty acid cycle after 35 years. Diabetes Metab Rev. 1998 Dec;14(4):263–283. doi: 10.1002/(sici)1099-0895(199812)14:4<263::aid-dmr233>3.0.co;2-c. [DOI] [PubMed] [Google Scholar]
  28. Rubins H. B., Robins S. J., Collins D., Fye C. L., Anderson J. W., Elam M. B., Faas F. H., Linares E., Schaefer E. J., Schectman G. Gemfibrozil for the secondary prevention of coronary heart disease in men with low levels of high-density lipoprotein cholesterol. Veterans Affairs High-Density Lipoprotein Cholesterol Intervention Trial Study Group. N Engl J Med. 1999 Aug 5;341(6):410–418. doi: 10.1056/NEJM199908053410604. [DOI] [PubMed] [Google Scholar]
  29. Saloranta C., Koivisto V., Widén E., Falholt K., DeFronzo R. A., Härkönen M., Groop L. Contribution of muscle and liver to glucose-fatty acid cycle in humans. Am J Physiol. 1993 Apr;264(4 Pt 1):E599–E605. doi: 10.1152/ajpendo.1993.264.4.E599. [DOI] [PubMed] [Google Scholar]
  30. Sniderman A. D., Scantlebury T., Cianflone K. Hypertriglyceridemic hyperapob: the unappreciated atherogenic dyslipoproteinemia in type 2 diabetes mellitus. Ann Intern Med. 2001 Sep 18;135(6):447–459. doi: 10.7326/0003-4819-135-6-200109180-00014. [DOI] [PubMed] [Google Scholar]
  31. Torra I. P., Chinetti G., Duval C., Fruchart J. C., Staels B. Peroxisome proliferator-activated receptors: from transcriptional control to clinical practice. Curr Opin Lipidol. 2001 Jun;12(3):245–254. doi: 10.1097/00041433-200106000-00002. [DOI] [PubMed] [Google Scholar]
  32. Unger R. H., Orci L. Lipotoxic diseases of nonadipose tissues in obesity. Int J Obes Relat Metab Disord. 2000 Nov;24 (Suppl 4):S28–S32. doi: 10.1038/sj.ijo.0801498. [DOI] [PubMed] [Google Scholar]
  33. Zhou Y. T., Grayburn P., Karim A., Shimabukuro M., Higa M., Baetens D., Orci L., Unger R. H. Lipotoxic heart disease in obese rats: implications for human obesity. Proc Natl Acad Sci U S A. 2000 Feb 15;97(4):1784–1789. doi: 10.1073/pnas.97.4.1784. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from Journal of the Royal Society of Medicine are provided here courtesy of Royal Society of Medicine Press

RESOURCES