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Exercise training decreases plasma leptin levels and the expression of hepatic leptin receptor-a, -b, and, -e in rats

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Abstract

In addition to acting in the central nervous system, leptin also acts on peripheral tissues such as liver to provide a protection against lipid accretion. Previous evidence from human and animal model indicates that exercise training reduces circulating leptin levels beyond the changes in adiposity levels. Because liver is one of the main peripheral organs for leptin action, this present study was designed to determine whether leptin receptors expression in liver is changed by exercise training. Female rats trained (TR) or kept sedentary (Sed) for 8 weeks were submitted either to a standard (SD) diet for 8 weeks or for 6 weeks followed by 2 weeks of high-fat (HF) or high-carbohydrate (HC) feeding. Food intake, adiposity levels, circulating plasma leptin and insulin concentrations along with the hepatic expression of leptin receptors (ObR-a, -b, and -e) and peroxisome proliferator-activated receptor α (PPARα) and peroxisome proliferator-activated receptor-gamma co-activator-1α (PGC-1α), were measured in all the animals. Intra-abdominal fat depots were increased under the HF but not under the HC diet. As expected, exercise training decreases intra-abdominal adiposity in animals fed with the SD and the HF diet, and to a lesser extent in HC-fed rats. Plasma leptin levels either expressed in absolute values or in values relative to adiposity levels were significantly (P < 0.05) increased with the HF diet and significantly decreased in TR animals, independently of the diet. Moreover, a significant (P < 0.01) reduction in hepatic gene expression of ObR-a, -b and -e was found in TR animals in all the three diet conditions. PPARα and PGC-1α mRNAs were also decreased (P < 0.05) in TR animals in two out of three diet conditions. The present findings indicate that exercise training-induced decrease in plasma leptin levels is accompanied by a reduction in gene expression of three different isoforms of leptin receptors in liver.

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References

  1. Bornstein SR, Abu-Asab M, Glasow A, Päth G, Hauner H, Tsokos M, Chrousos G, Scherbaum WA (2000) Immunohistochemical and ultrastructural localization of leptin and leptin receptor in human white adipose tissue and differentiating human adipose cells in primary culture. Diabetes 49:532–538. doi:10.2337/diabetes.49.4.532

    Article  PubMed  CAS  Google Scholar 

  2. Shirai Y, Yaku S, Suzuki M (2004) Metabolic regulation of leptin production in adipocytes: a role of fatty acid synthesis intermediates. J Nutr Biochem 15:651–656. doi:10.1016/j.jnutbio.2004.10.002

    Article  PubMed  CAS  Google Scholar 

  3. Cohen P, Miyazaki M, Socci ND, Hagge-Greenberg A, Liedtke W, Soukas AA, Sharma R, Hudgins LC, Ntambi JM, Friedman JM (2002) Role for stearoyl-CoA desaturase-1 in leptin-mediated weight loss. Science 297:240–243. doi:10.1126/science.1071527

    Article  PubMed  CAS  Google Scholar 

  4. Cohen P, Yang G, Yu X, Soukas AA, Wolfish CS, Friedman JM, Li C (2005) Induction of leptin receptor expression in the liver by leptin and food deprivation. J Biol Chem 280:10034–10039. doi:10.1074/jbc.M413684200

    Article  PubMed  CAS  Google Scholar 

  5. Unger RH (2003) The physiology of cellular liporegulation. Annu Rev Physiol 65:333–347. doi:10.1146/annurev.physiol.65.092101.142622

    Article  PubMed  CAS  Google Scholar 

  6. Muoio DM, Dohm GL, Fiedorek FT, Tapscott EB, Coleman RA (1997) Leptin directly alters lipid portioning in skeletal muscle. Diabetes 46:1360–1363. doi:10.2337/diabetes.46.8.1360

    Article  PubMed  CAS  Google Scholar 

  7. Guerra B, Santana A, Fuentes T, Delagdo-Guerra S, Cabrera-Socorro A, Dorado C, Calbet JA (2007) Leptin receptors in human skeletal muscle. J Appl Physiol 102:1786–1792. doi:10.1152/japplphysiol.01313.2006

    Article  PubMed  CAS  Google Scholar 

  8. Ge D, Gooljar SB, Kyriakou T, Collins LJ, Swaminathan R, Snider H, Spector TD, O’Dell SD (2008) Association of common JAK2 variants with body fat, insulin sensitivity and lipid profile. Obesity (Silver Spring) 16:492–496. doi:10.1038/oby.2007.79

    Article  CAS  Google Scholar 

  9. Zastrow O, Seidel B, Kiess W, Thiery J, Keller E, Böttner A, Kratzsch J (2003) The soluble leptin receptor is crucial for leptin action: evidence from clinical and experimental data. Int J Obes 27:1472–1478. doi:10.1038/sj.ijo.0802432

    Article  CAS  Google Scholar 

  10. Gauthier MS, Couturier K, Charbonneau A, Lavoie JM (2004) Effects of introducing physical training in the course of a 16-week high-fat diet regimen on hepatic steatosis, adipose tissue fat accumulation, and plasma lipid profile. Int J Obes Relat Metab Disord 28:1064–1071. doi:10.1038/sj.ijo.0802628

    Article  PubMed  Google Scholar 

  11. Hickey MS, Houmard JA, Considine RV, Tyndall GL, Midgette JB, Gavignan KE, Weidner ML, McCammon MR, Israel RG, Caro JF (1997) Gender-dependent effects of exercise training on serum leptin levels in humans. Am J Physiol 272:E562–E566

    PubMed  CAS  Google Scholar 

  12. Fernandez-Galaz C, Fernandez-Agullo T, Campoy F, Arribas C, Gallardo N, Andres A, Ros M, Carrascosa JM (2002) Long-term food restriction prevents ageing-associated central leptin resistance in wistar rats. Diabetologia 45:997–1003. doi:10.1007/s00125-002-0851-4

    Article  PubMed  CAS  Google Scholar 

  13. Miyazaki M, Dobrzyn A, Man WC, Chu K, Sampath H, Kim HJ, Ntambi JM (2004) Stearoyl-CoA desaturase 1 gene expression is necessary for fructose-mediated induction of lipogenic gene expression by sterol regulatory element-binding protein-1c-dependent and -independent mechanisms. J Biol Chem 279:25164–25171. doi:10.1074/jbc.M402781200

    Article  PubMed  CAS  Google Scholar 

  14. Gauthier MS, Favier R, Lavoie J-M (2006) Time course of the development of non-alcoholic hepatic steatosis in response to high-fat diet-induced obesity in rats. Br J Nutr 95:273–281. doi:10.1079/BJN20051635

    Article  PubMed  CAS  Google Scholar 

  15. Schaible TF, Scheuer J (1985) Cardiac adaptations to chronic exercise. Prog Cardiovasc Dis 27:234–297. doi:10.1016/S0033-0620(85)80001-3

    Article  Google Scholar 

  16. Hoffman-Goetz L, MacDonald MA (1983) Effect of treadmill exercise on food intake and body weight in lean and obese rats. Physiol Behav 31:343–346. doi:10.1016/0031-9384(83)90199-3

    Article  PubMed  CAS  Google Scholar 

  17. Bedford TG, Tipton CM, Wilson NC, Oppliger RA, Gisolfi CV (1979) Maximum oxygen consumption of rats and its changes with various experimental procedures. J Appl Physiol 47:1278–1283

    PubMed  CAS  Google Scholar 

  18. Krotkiewski M, Bjorntorp P (1976) The effect of progesterone and of insulin administration on regional adipose tissue cellularity in the rat. Acta Physiol Scand 96:122–127

    Article  PubMed  CAS  Google Scholar 

  19. Ailhaud G (2006) Adipose tissue as a secretory organ: from adipogenesis to the metabolic syndrome. C R Biol 329:570–577. doi:10.1016/j.crvi.2005.12.012

    Article  PubMed  CAS  Google Scholar 

  20. Pellizzon M, Buison A, Ordiz F Jr, Santa Ana L, Jen KL (2002) Effects of dietary fatty acids and exercise on body-weight regulation and metabolism in rats. Obes Res 10:947–955. doi:10.1038/oby.2002.129

    Article  PubMed  CAS  Google Scholar 

  21. Finck BN, Gropler MC, Chen Z, Leone TC, Croce MA, Harris TE, Lawrence JC, Kelly DP (2006) Lipin is an inducible amplifier of the hepatic PGC-1alpha/PPARalpha regulatory pathway. Cell Metab 4:199–210. doi:10.1016/j.cmet.2006.08.005

    Article  PubMed  CAS  Google Scholar 

  22. Saltin B, Astrand PO (1993) Free fatty acids and exercise. Am J Clin Nutr 57:752S–758S

    PubMed  CAS  Google Scholar 

  23. Rector RS, Thyfault JP, Morris RT, Laye MJ, Borengasser SJ, Booth FW, Ibdah JA (2008) Daily exercise increases hepatic fatty acid oxidation and prevents steatosis in Otsuka Long-Evans Tokushima Fatty (OLETF) rats. Am J Physiol Gastrointest Liver Physiol 294:G619–G626. doi:10.1152/ajpgi.00428.2007

    Article  PubMed  CAS  Google Scholar 

  24. Biddinger SB, Miyazaki M, Boucher J, Ntambi JM, Khan CR (2006) Leptin suppresses stearoyl-CoA desaturase 1 by mechanisms independent of insulin and sterol regulatory element binding protein-1c. Diabetes 55:2032–2041. doi:10.2337/db05-0742

    Article  PubMed  CAS  Google Scholar 

  25. Ntambi JM, Miyzaki M (2004) Regulation of stearoyl-CoA desaturases and role in metabolism. Prog Lipid Res 43:91–104. doi:10.1016/S0163-7827(03)00039-0

    Article  PubMed  CAS  Google Scholar 

  26. Cohen P, Zhao C, Cai X, Montez JM, Rohani SC, Feinstein P, Monbaerts P, Friedman JM (2001) Selective deletion of leptin receptor in neurons leads to obesity. J Clin Invest 108:113–1121

    Google Scholar 

  27. Lee Y, Wang MY, Kakuma T, Wang ZW, Babcock E, McCorkle K, Higa M, Zhou YT, Unger RH (2001) Liporegulation in diet-induced obesity. The antisteatotic role of hyperleptinemia. J Biol Chem 276:5629–5635. doi:10.1074/jbc.M008553200

    Article  PubMed  CAS  Google Scholar 

  28. Patterson CM, Levin BE (2008) Role of exercise in the central regulation of energy homeostasis and in the prevention of obesity. Neuroendocrinology 87:65–70. doi:10.1159/000100982

    Article  PubMed  CAS  Google Scholar 

  29. Javor ED, Ghany MG, Cochran EK, Oral EA, DePaoli AM, Premkumar A, Kleiner DE, Gorden P (2005) Leptin reverses nonalcoholic steatohepatitis in patients with severe lipodystrophy. Hepatology 41:753–760. doi:10.1002/hep.20672

    Article  PubMed  CAS  Google Scholar 

  30. Levin BE, Dunn-Meynell AA (2006) Differential effects of exercise on body weight gain and adiposity in obesity-prone and -resistant rats. Int J Obes 30:722–727. doi:10.1038/sj.ijo.0803192

    Article  CAS  Google Scholar 

  31. Cohen SE, Kokkotou E, Biddinger SB, Kondo T, Gebhardt R, Kratzsch J, Mantzoros CS, Kahn CR (2007) High circulating leptin receptors with normal leptin sensitivity in liver-specific insulin receptor knock-out (LIRKO) mice. J Biol Chem 282:23672–23678. doi:10.1074/jbc.M704053200

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgements

This research was supported by the Natural Sciences and Engineering Research Council of Canada (to JM Lavoie), and the Canadian Institutes of Health Research (T 0602145.02 to JM Lavoie and D. Prud’homme, and MOP-53217, MOP-62901 to J. Gutkowska and M. Jankowski).

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Authors and Affiliations

  1. Department of Kinesiology, University of Montreal, Montreal, Canada

    Siham Yasari & Jean-Marc Lavoie

  2. Behavioural and Metabolic Research Unit, Montfort Hospital, University of Ottawa, 713, Montreal Road, Pavilion B, 1st Floor, Ottawa, ON, K1K 0T2, Canada

    Siham Yasari & Denis Prud’homme

  3. Research Center, Cardiovascular Biochemistry Laboratory, CHUM-Hôtel-Dieu, University of Montreal, Montreal, Canada

    Donghao Wang, Marek Jankowski & Jolanta Gutkowska

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  1. Siham Yasari
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  2. Donghao Wang
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Correspondence to Siham Yasari.

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Yasari, S., Wang, D., Prud’homme, D. et al. Exercise training decreases plasma leptin levels and the expression of hepatic leptin receptor-a, -b, and, -e in rats. Mol Cell Biochem 324, 13–20 (2009). https://doi.org/10.1007/s11010-008-9979-y

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