L-Carnitine Reduces Obesity Caused by High-Fat Diet in C57BL/6J Mice

  • Mun, Eun-Gyeng (Department of Food Science and Human Nutrition, College of Human Ecology, Chonbuk National University) ;
  • Soh, Ju-Ryoun (Department of Food Science and Human Nutrition, College of Human Ecology, Chonbuk National University) ;
  • Cha, Youn-Soo (Department of Food Science and Human Nutrition, College of Human Ecology, Chonbuk National University)
  • Published : 2007.04.30

Abstract

This study evaluated the effects of carnitine supplementation on obesity caused by a high-fat diet in C57BL/6J mice. The mice were fed a normal diet (ND), high-fat diet (HD), or carnitine-supplemented (0.5% of diet) high-fat diet (HDC) for 12 weeks. The results showed that body weight, energy intake, and feed intake were lower in the HDC group than the control groups. Acid-soluble acylcarnitine (A SAC), acid-insoluble acylcarnitine (AIAC), and total carnitine (TCNE) in the serum and liver were significantly higher in the HDC group. Hepatic carnitine palmitoyl transferase-I activity was significantly higher in the HDC group than the control groups. Acyl-coA synthetase (ACS) and carnitine palmitoyl transferase-I (CPT-I) mRNA expression in the liver was highest in the HDC group, however hepatic acetyl-coA carboxylase (ACC) mRNA expression in this group was lowest. Serum leptin levels and abdominal fat weight were lowest in the HDC group. We concluded that L-carnitine supplementation diminished the risk of obesity caused by a high-fat diet.

References

  1. Wardlaw GM, Kessel MW. Perspectives in Nutrition. 5th ed. McGraw Hill, NY, USA. pp. 17,404,669 (2002)
  2. Petro AE, Cotter J, Cooper DA, Peters JC, Surwit SJ, Surwit RS. Fat, carbohydrate, and calories in the development of diabetes and obesity in the C57BL/6J mouse. Metabolism 53: 454-457 (2004) https://doi.org/10.1016/j.metabol.2003.11.018
  3. Kim SJ, Sohn I, Lee YS, Lee YS. Hepatic gene expression profiles are altered by genistein supplementation in mice with diet-induced obesity. J. Nutr. 135: 33-41 (2005) https://doi.org/10.1093/jn/135.1.33
  4. Heo K, Odie J, Han IK, Cho W, Seo S, van Heugten E, Pilkington DH. Dietary L-camitine improves nitrogen utilization in growing pigs fed low energy, fat-containing diets. J. Nutr. 130: 1809-1814 (2000)
  5. LaBadie J, Dunn WA, Aronson NN Jr. Hepatic synthesis of camitine from protein-bound trimethyl-Iysine. Lysosomal digestion of methyl-lysine-labelled asialo-fetuin. Biochem. J. 160: 85-95 (1976) https://doi.org/10.1042/bj1600085
  6. Brass EP, Hoppel CL. Camitine metabolism in the fasting rat. J. BioI. Chem. 253: 2688-2693 (1978)
  7. Lin X, Chavez MR, Bruch RC, Kilroy GE, Simmons LA, Lin L, Braymer HD, Bray GA, York DA. The effects of a high-fat diet on leptin mRNA, serum leptin, and the response to leptin are not altered in a rat strain susceptible to high-fat diet-induced obesity. J. Nutr. 128: 1606-1613 (1998)
  8. Woeltje KF, Kuwajima M, Foster DW, McGarry JD. Characterization of the mitochondrial camitine palmitoyltransferase enzyme system. J. BioI. Chem. 262: 9822-9827 (1987)
  9. Majerus PW, Kilburn E. Acetyl Coenzyme A Carboxylase. J. BioI. Chem. 244: 6254-6262 (1969)
  10. Kalra SP, Dube MG, Pu S, Xu B, Horvath TL, Kalra PS. Interacting appetite-regulating pathways in the hypothalamic regulation of body weight. Endocr. Rev. 20: 68-100 (1999) https://doi.org/10.1210/er.20.1.68
  11. Kopelman P. Obesity as a medical problem. Nature 404: 635-643 (2000) https://doi.org/10.1038/35007508
  12. Deng K, Wong CW, Nolan JV. Long-term effects of early-life dietary L-camitine on lymphoid organs and immune responses in Leghorn-type chickens. J. Anim. Physiol. An. N. 90: 81-86 (2006) https://doi.org/10.1111/j.1439-0396.2005.00569.x
  13. Hoppel CI, Genuth SM. Camitine metabolism in normal-weight and obese human subjects during fasting. Am. J. Pysiol. 238: 409-415 (1980)
  14. Almind K, Kahn CR. Genetic determinants of energy expenditure and insulin resistance in diet-induced obesity in mice. Diabetes 53: 3274-3285 (2004) https://doi.org/10.2337/diabetes.53.12.3274
  15. Geelen SN, Blazquez C, Geelen MJ, Sloet van Oldruitenborgh Oosterbaan MM, Beynen AC. High-fat intake lowers hepatic fatty acid synthesis and raises fatty acid oxidation in aerobic muscle in Shetland ponies. Brit. J. Nutr. 86: 31-36 (2001) https://doi.org/10.1079/BJN2001364
  16. Reda E, D'Iddio S, Nicolai R, Benatti P, Calvain M. The carnitine system and body composition. Acta Diabetol. 40: 106-113 (2003) https://doi.org/10.1007/s00592-003-0040-z
  17. Malone JI, Cuthbertson DD, Malone MA, Schocken DD. Cardioprotective effects of camitine in streptozotocin-induced diabetic rats. Cardiovasc. Diabetol. 5: 1-6 (2006) https://doi.org/10.1186/1475-2840-5-1
  18. Heo YR, Lee Y, Cha YS. L-Camitine administration improves lipid metabolism in streptozotocin-induced diabetic rat. Nutr. Sci. 5: 3-8 (2002)
  19. Terauchi Y, Matsui J, Kamon J, Yamauchi T, Kubota N, Komeda K, Aizawa S, Akanuma Y, Tomita M, Kadowaki T. Increased serum leptin protects from adiposity despite the increased glucose uptake in white adipose tissue in mice lacking p85alpha phosphoinositide 3-kinase. Diabetes 53: 2261-2270 (2004) https://doi.org/10.2337/diabetes.53.9.2261
  20. Johnson D, Lardy H. Isolation of liver or kidney mitochondria. pp. 94-96. In: Methods in Enzymology. Estabrook RW (ed). Academic Press, New York, NY, USA (1967)
  21. Lee MS, Kim JS, Lee HS, Kim YH. L-Camitine stimulates lipolysis via induction of lipolytic gene and suppression of lipogenic gene expression in 3T3-L1 adipocytes (Pl-11). In: Abstracts: Annual Meeting and International Symposium. November 3-5, Hotel Concorde, Gyeongju, Korea. The Korean Nutrition Society, Seoul, Korea (2005)
  22. Soh JR, Cha YS. Gamma-aminobutyric acid and/or camitine supplementation alters lipid and some immune related nutrient levels in mice. J. Food Sci. Nutr. 9: 58-64 (2004) https://doi.org/10.3746/jfn.2004.9.1.058
  23. Chung EJ, Um YS, Cha YS, Park TS. Effects of short-term supplementation of camitine on plasma and urinary camitine and plasma lipid levels of healthy male adults. Korean J. Nutr. 36: 720-728 (2003)
  24. Nelson DL, Cox MM. Lehninger Principles of Biochemistry. 3th ed. Worth, NY, USA. p. 603 (2000)
  25. Yamashita S, Nakamura T, Shimomura I, Nishida M, Yoshida S, Kotani K, Kameda-Takemuara K, Tokunaga K, Matsuzawa Y. Insulin resistance and body fat distribution. Diabetes Care 19: 287-291 (1996) https://doi.org/10.2337/diacare.19.3.287
  26. Feng Y, Guo C, Wei J, Yang J, Ge Y, Gao L. Necessity of carnitine supplementation in semi starved rats fed a high-fat diet. Nutrition 17: 628-631 (2001) https://doi.org/10.1016/S0899-9007(01)00601-3
  27. Peffer PL, Lin X, Odie J. Hepatic beta-oxidation and camitine palmitoyltransferase I in neonatal pigs after dietary treatments of clofibric acid, isoproterenol, and medium-chain triglycerides. Am. J. Physiol. Reg. I. 288: 1518-1524 (2005)
  28. Feoli AM, Roehrig C, Rotta LN, Kruger AH, Souza KB, Kessler AM, Renz SV, Brusque AM, Souza DO, Perry MLS. Serum and liver lipids in rats and chicks fed with diets containing different oils. Nutrition 19: 789-793 (2003) https://doi.org/10.1016/S0899-9007(03)00106-0
  29. Kunau WH, Dommes V, Schulz H. Beta-oxidation of fatty acids in mitochondria, peroxisomes, and bacteria: a century of continued progress. Prog. Lipid Res. 34: 267-342 (1995) https://doi.org/10.1016/0163-7827(95)00011-9
  30. Suzuki H, Kawarabayasi Y, Kondo J, Abe T, Nishikawa K, Kimura S, Hashimoto T, Yamamoto T. Structure and regulation of rat lingchain acyl-CoA synthetase. J. BioI. Chem. 265: 8681-8685 (1990)
  31. Ramsay RR, Gandour RD, van der Leij FR. Molecular enzymology of camitine transfer and transport. Biochim. Biophys. Acta 1546: 21-43 (2001) https://doi.org/10.1016/S0167-4838(01)00147-9
  32. Guzman M, Castro J, Maquedano A. Ethanol feeding to rats reversibly decreases hepatic camitine palmitoyltransferase activity and increases enzyme sensitivity to malonyl-CoA. Biochem. Bioph. Res. Co. 149: 443-448 (1987) https://doi.org/10.1016/0006-291X(87)90387-1
  33. Cederblad G, Lindstedt S. Excretion of L-camitine in man. Clin. Chim. Acta 33: 117-123 (1972)
  34. Brass EP. Supplemental camtine and exercise. Am. J. Clin. Nutr. 72: 618-623 (2000) https://doi.org/10.1093/ajcn/72.2.618S
  35. Schaub B, von Mutius E. Obesity and asthma, what are the links? Curr. Opin. Allergy Cl. 5: 185-193 (2005) https://doi.org/10.1097/01.all.0000162313.64308.b5
  36. Bray GA. Medical consequence of obesity. J. Clin. Endocr. Metab. 89: 2583-2589 (2004) https://doi.org/10.1210/jc.2004-0535
  37. Birkenfeld C, Doberenz J, Kluge H, Eder K. Effect of L-carnitine supplementation of sows on L-camitine status, body composition, and concentrations of lipids in liver and plasma of their piglets at birth and during the suckling period. Anim. Feed Sci. Tech. 129: 23-38 (2006) https://doi.org/10.1016/j.anifeedsci.2005.12.007
  38. Hirsch J. The search for new ways to treat obesity. P. Natl. Acad. Sci. USA 99: 9096-9097 (2002) https://doi.org/10.1073/pnas.152327099
  39. Tong L. Acetyl-coenzyme A carboxylase: crucial metabolic enzyme and attractive target for drug discovery. Cell Mol. Life Sci. 62: 1784-1803 (2005) https://doi.org/10.1007/s00018-005-5121-4