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Dietary Protein Restriction Alters Lipid Metabolism and Insulin Sensitivity in Rats

  • Kang, W. ;
  • Lee, M.S. ;
  • Baik, M.
  • Received : 2010.11.26
  • Accepted : 2011.02.18
  • Published : 2011.09.01

Abstract

Dietary protein restriction affects lipid metabolism in rats. This study was performed to determine the effect of a low protein diet on hepatic lipid metabolism and insulin sensitivity in growing male rats. Growing rats were fed either a control 20% protein diet or an 8% low protein diet. Feeding a low protein diet for four weeks from 8 weeks of age induced a fatty liver. Expression of acetyl-CoA carboxylase, a key lipogenic enzyme, was increased in rats fed a low protein diet. Feeding a low protein diet decreased very low density lipoprotein (VLDL) secretion without statistical significance. Feeding a low protein diet down-regulated protein expression of microsomal triglyceride transfer protein, an important enzyme of VLDL secretion. Feeding a low protein diet increased serum adiponectin levels. We performed glucose tolerance test (GTT) and insulin tolerance test (ITT). Both GTT and ITT were increased in protein-restricted growing rats. Our results demonstrate that dietary protein restriction increases insulin sensitivity and that this could be due to low-protein diet-mediated metabolic adaptation. In addition, increased adiponectin levels may influences insulin sensitivity. In conclusion, dietary protein restriction induces a fatty liver. Both increased lipogenesis and decreased VLDL secretion has contributed to this metabolic changes. In addition, insulin resistance was not associated with fatty liver induced by protein restriction.

Keywords

Dietary Protein Restriction;Fatty Liver;Lipid Metabolism;Insulin Sensitivity

References

  1. Aparecida de Franca, S., M. P. Dos Santos, M. A. Garofalo, L. C. Navegantes, C. Kettelhut Ido, C. F. Lopes and N. H. Kawashita. 2009. Low protein diet changes the energetic balance and sympathetic activity in brown adipose tissue of growing rats. Nutrition 25:1186-1192. https://doi.org/10.1016/j.nut.2009.03.011
  2. Ascaso, J. F. 2010. Advances in cholesterol-lowering interventions. Endocrinol. Nutr. 57:210-219. https://doi.org/10.1016/j.endonu.2010.03.008
  3. Atkinson, L. L., S. E. Kelly, J. C. Russell, J. Bar-Tana and G. D. Lopaschuk. 2002. MEDICA 16 inhibits hepatic acetyl-CoA carboxylase and reduces plasma triacylglycerol levels in insulin-resistant JCR: LA-cp rats. Diabetes 51:1548-1555. https://doi.org/10.2337/diabetes.51.5.1548
  4. Begriche, K., A. Igoudjil, D. Pessayre and B. Fromenty. 2006. Mitochondrial dysfunction in NASH: causes, consequences and possible means to prevent it. Mitochondrion 6:1-28.
  5. Cano, A., F. Ciaffoni, G. M. Safwat, P. Aspichueta, B. Ochoa, E. Bravo and K. M. Botham. 2009. Hepatic VLDL assembly is disturbed in a rat model of nonalcoholic fatty liver disease: is there a role for dietary coenzyme Q? J. Appl. Physiol. 107:707-717.
  6. Chang, B. H., W. Liao, L. Li, M. Nakamuta, D. Mack and L. Chan. 1999. Liver-specific inactivation of the abetalipoproteinemia gene completely abrogates very low density lipoprotein/low density lipoprotein production in a viable conditional knockout mouse. J. Biol. Chem. 274:6051-6055. https://doi.org/10.1074/jbc.274.10.6051
  7. del Rincon, J. P., K. Iida, B. D. Gaylinn, C. E. McCurdy, J. W. Leitner, L. A. Barbour, J. J. Kopchick, J. E. Friedman, B. Draznin and M. O. Thorner. 2007. Growth hormone regulation of p85alpha expression and phosphoinositide 3-kinase activity in adipose tissue: mechanism for growth hormone-mediated insulin resistance. Diabetes 56:1638-1646. https://doi.org/10.2337/db06-0299
  8. Fiaschi, T., F. Buricchi, G. Cozzi, S. Matthias, M. Parri, G. Raugei, G. Ramponi and P. Chiarugi. 2007. Redox-dependent and ligand-independent trans-activation of insulin receptor by globular adiponectin. Hepatology 46:130-139. https://doi.org/10.1002/hep.21643
  9. Folch, J., M. Lees and G. H. Sloane Stanley. 1957. A simple method for the isolation and purification of total lipids from animal tissues. J. Biol. Chem. 226:497-509.
  10. Fujita, K., Y. Nozaki, K. Wada, M. Yoneda, Y. Fujimoto, M. Fujitake, H. Endo, H. Takahashi, M. Inamori, N. Kobayashi, H. Kirikoshi, K. Kubota, S. Saito and A. Nakajima. 2009. Dysfunctional very-low-density lipoprotein synthesis and release is a key factor in nonalcoholic steatohepatitis pathogenesis. Hepatology 50:772-780. https://doi.org/10.1002/hep.23094
  11. Ikejima, K., K. Okumura, K. Kon, Y. Takei and N. Sato. 2007. Role of adipocytokines in hepatic fibrogenesis. J. Gastroenterol. Hepatol. Suppl. 1:S87-92.
  12. Kim, J. Y., E. van de Wall, M. Laplante, A. Azzara, M. E. Trujillo, S. M. Hofmann, T. Schraw, J. L. Durand, H. Li, G. Li, L. A. Jeilcks, M. F. Mehier, D. Y. Hui, Y. Deshaies, G. I. Shulman, G. J. Schwartz and P. E. Scherer. 2007. Obesity-associated improvements in metabolic profile through expansion of adipose tissue. J. Clin. Invest. 117:2621-2637. https://doi.org/10.1172/JCI31021
  13. Marchesini, G. and G. Forlani. 2002. NASH: from liver diseases to metabolic disorders and back to clinical hepatology. Hepatology 35:497-499. https://doi.org/10.1053/jhep.2002.31551
  14. Marra, F. and C. Bertolani. 2009. Adipokines in liver diseases. Hepatology 50:957-969. https://doi.org/10.1002/hep.23046
  15. Minehira, K., S. G. Young, C. J. Villanueva, L. Yetukuri, M. Oresic, M. K. Hellerstein, R. V. jr Farese, J. D. Horton, F. Preitner, B. Thorens and L. Tappy. 2008. Blocking VLDL secretion causes hepatic steatosis but does not affect peripheral lipid stores or insulin sensitivity in mice. J. Lipid Res. 49:2038-2044. https://doi.org/10.1194/jlr.M800248-JLR200
  16. Morris, L., D. Arata and D. C. Cederquist. 1965. Fatty livers in weanling rats fed a low protein, threonine-deficient diet. I. Effect of various diet fats. J. Nutr. 85:362-366.
  17. Postic, C. and J. Girard. 2008. The role of the lipogenic pathway in the development of hepatic steatosis. Diabetes Metab. 34:643-648. https://doi.org/10.1016/S1262-3636(08)74599-3
  18. Rothwell, N. J., M. J. Stock and R. S. Tyzbir. 1983. Mechanisms of thermogenesis induced by low protein diets. Metabolism 32:257-261. https://doi.org/10.1016/0026-0495(83)90190-7
  19. Singal, S. A., S. J. Hazan, V. P. Sydenstricker and J. M. Littlejohn. 1953. The production of fatty livers in rats on threonine-and lysine-deficient diets. J. Biol. Chem. 200:867-874.
  20. Therond, P. 2009. Catabolism of lipoproteins and metabolic syndrome. Curr. Opin. Clin. Nutr. Metab. Care 12:366-371. https://doi.org/10.1097/MCO.0b013e32832c5a12
  21. Theys, N., T. Bouckenooghe, M. T. Ahn, C. Remacle and B. Reusens. 2009. Maternal low-protein diet alters pancreatic islet mitochondrial function in a sex-specific manner in the adult rat. Am. J. Physiol. Regul. Integr. Comp. Physiol. 297:1516-1525. https://doi.org/10.1152/ajpregu.00280.2009
  22. Thonney, M. L. amd D. A. Ross. 1987. Composition of gain of rats fed low or high protein diets and grown at controlled rates from 80 to 205 grams. J. Nutr. 117:2135-2141.
  23. Tilg, H. and G. S. Hotamisligil. 2006. Nonalcoholic fatty liver disease: Cytokine-adipokine interplay and regulation of insulin resistance. Gastroenterology 131:934-945. https://doi.org/10.1053/j.gastro.2006.05.054
  24. White, B. D., B. He, R. G. Dean and R. J. Martin. 1994. Low protein diets increase neuropeptide Y gene expression in the basomedial hypothalamus of rats. J. Nutr. 124:1152-1160.
  25. White, B. D., M. H. Porter and R. J. Martin. 2000a. Effects of age on the feeding response to moderately low dietary protein in rats. Physiol. Behav. 68:673-681. https://doi.org/10.1016/S0031-9384(99)00229-2
  26. White, B. D., M. H. Porter and R. J. Martin. 2000b. Protein selection, food intake, and body composition in response to the amount of dietary protein. Physiol. Behav. 69:383-598. https://doi.org/10.1016/S0031-9384(99)00232-2
  27. Yamaguchi, K., L. Yang, S. McCall, J. Huang, X. X. Yu, S. K. Pandey, S. Bhanot, B. P. Monia, Y. X. Li and A. M. Diehl. 2007. Inhibiting triglyceride synthesis improves hepatic steatosis but exacerbates liver damage and fibrosis in obese mice with nonalcoholic steatohepatitis. Hepatology 45:1366-1374. https://doi.org/10.1002/hep.21655
  28. Yan, X., F. Zhang, D. Li, X. Zhu and Z. Jia. 2010. Effects of chromium on energy metabolism in lambs fed with different dietary protein levels. Asian-Aust. J. Anim. Sci. 23:205-212.

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