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Dietary Aloe QDM Complex Reduces Obesity-Induced Insulin Resistance and Adipogenesis in Obese Mice Fed a High-Fat Diet

  • Received : 2012.05.11
  • Accepted : 2012.05.31
  • Published : 2012.06.30
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Abstract

Obesity-induced disorders contribute to the development of metabolic diseases such as insulin resistance, fatty liver diseases, and type 2 diabetes (T2D). In this study, we evaluated whether the Aloe QDM complex could improve metabolic disorders related to blood glucose levels and insulin resistance. Male C57BL/6 obese mice fed a high-fat diet for 54 days received a supplement of Aloe QDM complex or pioglitazone (PGZ) or metformin (Met) and were compared with unsupplemented controls (high-fat diet; HFD) or mice fed a regular diet (RD). RT-PCR and western blot analysis were used to quantify the expression of obesity-induced inflammation. Dietary Aloe QDM complex lowered body weight, fasting blood glucose, plasma insulin, and leptin levels, and markedly reduced the impairment of glucose tolerance in obese mice. Also, Aloe QDM complex significantly enhanced plasma adiponectin levels and insulin sensitivity via AMPK activity in muscles. At the same time, Aloe QDM decreased the mRNA and protein of $PPAR{\gamma}/LXR{\alpha}$ and scavenger receptors in white adipose tissue (WAT). Dietary Aloe QDM complex reduces obesity-induced glucose tolerance not only by suppressing $PPAR{\gamma}/LXR{\alpha}$ but also by enhancing AMPK activity in the WAT and muscles, both of which are important peripheral tissues affecting insulin resistance. The Aloe QDM complex could be used as a nutritional intervention against T2D.

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References

  1. Weiser, M., W. H. Frishman, M. D. Michaelson, and M. A. Abdeen. 1997. The pharmacologic approach to the treatment of obesity. J. Clin. Pharmacol. 37: 453-473. https://doi.org/10.1002/j.1552-4604.1997.tb04323.x
  2. Surwit, R. S., C. M. Kuhn, C. Cochrane, J. A. McCubbin, and M. N. Feinglos. 1988. Diet-induced type II diabetes in C57BL/6J mice. Diabetes 37: 1163-1167. https://doi.org/10.2337/diabetes.37.9.1163
  3. Stunkard, A. J. 1996. Current views on obesity. Am. J. Med. 100: 230-236. https://doi.org/10.1016/S0002-9343(97)89464-8
  4. Nicolai, A., M. Li, D. H. Kim, S. J. Peterson, L. Vanella, V. Positano, A. Gastaldelli, R. Rezzani, L. F. Rodella, G. Drummond, C. Kusmic, A. L'Abbate, A. Kappas, and N. G. Abraham. 2009. Heme oxygenase-1 induction remodels adipose tissue and improves insulin sensitivity in obesity-induced diabetic rats. Hypertension 53: 508-515. https://doi.org/10.1161/HYPERTENSIONAHA.108.124701
  5. Peterson, S. J., D. H. Kim, M. Li, V. Positano, L. Vanella, L. F. Rodella, F. Piccolomini, N. Puri, A. Gastaldelli, C. Kusmic, A. L'Abbate, and N. G. Abraham. 2009. The L-4F mimetic peptide prevents insulin resistance through increased levels of HO-1, pAMPK, and pAKT in obese mice. J. Lipid. Res. 50: 1293-1304. https://doi.org/10.1194/jlr.M800610-JLR200
  6. Porstmann, T., C. R. Santos, B. Griffiths, M. Cully, M. Wu, S. Leevers, J. R. Griffiths, Y. L. Chung, and A. Schulze. 2008. SREBP activity is regulated by mTORC1 and contributes to Akt-dependent cell growth. Cell Metab. 8: 224-236. https://doi.org/10.1016/j.cmet.2008.07.007
  7. Wellen, K. E., and G. S. Hotamisligil. 2005. Inflammation, stress, and diabetes. J. Clin. Invest. 115: 1111-1119.
  8. Rajala, M. W., and P. E. Scherer. 2003. Minireview: The adipocyte-- at the crossroads of energy homeostasis, inflammation, and atherosclerosis. Endocrinology. 144: 3765- 3773. https://doi.org/10.1210/en.2003-0580
  9. Weisberg, S. P., D. McCann, M. Desai, M. Rosenbaum, R. L. Leibel, and A. W. Jr. Ferrante. 2003. Obesity is associated with macrophage accumulation in adipose tissue. J. Clin. Invest. 112: 1796-1808.
  10. Xu, H., G. T. Barnes, Q. Yang, G. Tan, D. Yang, C. J. Chou, J. Sole, A. Nichols, J. S. Ross, L. A. Tartaglia, and H. Chen. 2003. Chronic inflammation in fat plays a crucial role in the development of obesity-related insulin resistance. J. Clin. Invest. 112: 1821-1830.
  11. Hardie, D. G., and D. Carling. 1997. The AMP-activated protein kinase--fuel gauge of the mammalian cell? Eur. J. Biochem. 246: 259-273. https://doi.org/10.1111/j.1432-1033.1997.00259.x
  12. Sag, D., D. Carling, R. D. Stout, and J. Suttles. 2008. Adenosine 5'-monophosphate-activated protein kinase promotes macrophage polarization to an anti-inflammatory functional phenotype. J. Immunol. 181: 8633-8641. https://doi.org/10.4049/jimmunol.181.12.8633
  13. Makinde, A. O., J. Gamble., and G. D. Lopaschuk. 1997. Upregulation of 5'-AMP-activated protein kinase is responsible for the increase in myocardial fatty acid oxidation rates following birth in the newborn rabbit. Circ. Res. 80: 482-489. https://doi.org/10.1161/01.RES.80.4.482
  14. Zong, H., J. M. Ren, L. H. Young, M. Pypaert, J. Mu, M. J. Birnbaum, and G. I. Shulman. 2002. AMP kinase is required for mitochondrial biogenesis in skeletal muscle in response to chronic energy deprivation. Proc. Natl. Acad. Sci. U. S. A. 99: 15983-15987. https://doi.org/10.1073/pnas.252625599
  15. Ju, J. S., M. A. Gitcho, C. A. Casmaer, P. B. Patil, D. G. Han, S. A. Spencer, and J. S. Fisher. 2007. Potentiation of insulin-stimulated glucose transport by the AMP-activated protein kinase. Am. J. Physiol. Cell Physiol. 292: C564-572. https://doi.org/10.1152/ajpcell.00269.2006
  16. Iglesias, M. A., J. M. Ye, G. Frangioudakis, A. K. Saha, E. Tomas, N. B. Ruderman, G. J. Cooney, and E. W. Kraegen. 2002. AICAR administration causes an apparent enhancement of muscle and liver insulin action in insulin-resistant high-fatfed rats. Diabetes 51: 2886-2894. https://doi.org/10.2337/diabetes.51.10.2886
  17. Josep, B. R., G. Amir, K. Jennifer, and H. Raquel. 2005. Peroxisome proliferator activated receptors: the nutritionally controlled molecular networks that integrate inflammation, immunity and metabolism. Current Nutrition & Food Science 1: 179-187. https://doi.org/10.2174/1573401054022619
  18. Hardie, D. G. 2007. AMP-activated protein kinase as a drug target. Annu. Rev. Pharmacol. Toxicol. 47: 185-210. https://doi.org/10.1146/annurev.pharmtox.47.120505.105304
  19. Hardie, D. G., D. Carling, and M. Carlson. 1998. The AMP-activated/SNF1 protein kinase subfamily: metabolic sensors of the eukaryotic cell? Annu. Rev. Biochem. 67: 821-855. https://doi.org/10.1146/annurev.biochem.67.1.821
  20. Capasso, F., F. Borrelli, R. Capasso, Carlo G. Di, A. Izzo, L. Pinto, N. Mascolo, S. Castaldo, and R. Longo. 1998. Aloe and its therapeutic use. Phytother. Res. 12: S124-127. https://doi.org/10.1002/(SICI)1099-1573(1998)12:1+3.0.CO;2-X
  21. Heggers, J. P., A. Kucukcelebi, C. J. Stabenau, F. Ko, L. D. Broemeling, M. C. Robson, and W.D. Winters. 1995. Wound healing effects of Aloe gel and other topical antibacterial agents on rat skin. Phytother. Res. 9: 455-457. https://doi.org/10.1002/ptr.2650090615
  22. Koo, M. W. L. 1994. Aloe vera: Antiulcer and antidiabetic effects. Phytother. Res. 8: 461-464. https://doi.org/10.1002/ptr.2650080805
  23. Winters, W.D., R. Benavides, and W. J. Clouse. 1981. Effects of aloe extracts on human normal and tumor cells in vitro. Econ. Bot. 35: 89-95. https://doi.org/10.1007/BF02859219
  24. Yongchaiyudha, S., V. Rungpitarangsi, N. Bunyapraphatsara, and O. Chokechaijaroenporn. 1996. Antidiabetic activity of Aloe vera L. juice. I. Clinical trial in new cases of diabetes mellitus. Phytomedicine. 3: 241-243. https://doi.org/10.1016/S0944-7113(96)80060-2
  25. Bunyapraphatsara, N., S. Yongchaiyudha, V. Rungpitarangsi, and O. Chokechaijaroenporn. 1996. Antidiabetic activity of Aloe vera L. juice: II. Clinical trial in diabetes mellitus patients in combination with glibenclamide. Phytomedicine. 3: 245-248. https://doi.org/10.1016/S0944-7113(96)80061-4
  26. Kong, H., S. Lee, S. Shin, J. Kwon, T. H. Jo, E. Shin, K. S. Shim, Y. I. Park, C. K. Lee, and K. Kim. 2010. Down-regulation of adipogenesis and hyperglycemia in diet-induced obesity mouse model by Aloe QDM. Biomolecules & Therapeuticss 18: 336-342. https://doi.org/10.4062/biomolther.2010.18.3.336
  27. Kim, J. O., K. S. Kim, G. D. Lee, and J. H. Kwon. 2009. Antihyperglycemic and antioxidative effects of new herbal formula in streptozotocin-induced diabetic rats. J. Med. Food. 12: 728-735. https://doi.org/10.1089/jmf.2008.1195
  28. Kim, K., H. Kim, J. Kwon, S. Lee, H. Kong, S. A. Im, Y. H. Lee, Y. R. Lee, S. T. Oh, T. H. Jo, Y. I. Park, C. K. Lee, and K. Kim. 2009. Hypoglycemic and hypolipidemic effects of processed Aloe vera gel in a mouse model of non-insulin- dependent diabetes mellitus. Phytomedicine. 16: 856-863. https://doi.org/10.1016/j.phymed.2009.02.014
  29. Martin-Fuentes, P., F. Civeira, D. Recalde, A. L. Garcia-Otin, E. Jarauta, I. Marzo, and A. Cenarro. 2007. Individual variation of scavenger receptor expression in human macrophages with oxidized low-density lipoprotein is associated with a differential inflammatory response. J. Immunol. 179: 3242-3248. https://doi.org/10.4049/jimmunol.179.5.3242
  30. Stewart, C. R., L. M. Stuart, K. Wilkinson, J. M. van Gils, J. Deng, A. Halle, K. J. Rayner, L. Boyer, R. Zhong, W. A. Frazier, A. Lacy-Hulbert, J. El Khoury, D. T. Golenbock, and K. J. Moore. 2010. CD36 ligands promote sterile inflammation through assembly of a Toll-like receptor 4 and 6 heterodimer. Nat. Immunol. 11: 155-161. https://doi.org/10.1038/ni.1836
  31. Sahoo, D., and V. Drover. 2006. The role of scavenger receptors in signaling, inflammation and atherosclerosis. Biochemistry of Atherosclerosis. 1: 70-91.
  32. Peiser, L., and S. Gordon. 2001. The function of scavenger receptors expressed by macrophages and their role in the regulation of inflammation. Microbes. Infect. 3:149-159. https://doi.org/10.1016/S1286-4579(00)01362-9
  33. Stewart, C. R., L. M. Stuart, K. Wilkinson, J. M. van Gils, J. Deng, A. Halle, K. J. Rayner, L. Boyer, R. Zhong, W. A. Frazier, A. Lacy-Hulbert, J. El Khoury, D. T. Golenbock, and K. J. Moore. 2010. CD36 ligands promote sterile inflammation through assembly of a Toll-like receptor 4 and 6 heterodimer. Nat. Immunol. 11: 155-161. https://doi.org/10.1038/ni.1836
  34. Hoebe, K., P. Georgel, S. Rutschmann, X. Du, S. Mudd, K. Crozat, S. L. Sovath, Shamel, T. Hartung, U. Zähringer, and B. Beutler. 2005. CD36 is a sensor of diacylglycerides. Nature. 433: 523-527. https://doi.org/10.1038/nature03253
  35. Stuart, L. M., J. Deng, J. M. Silver, K. Takahashi, A. A. Tseng, E. J. Hennessy, R. A. Ezekowitz, and K. J. Moore. 2005. Response to Staphylococcus aureus requires CD36-mediated phagocytosis triggered by the COOH-terminal cytoplasmic domain. J Cell Biol. 170: 477-485. https://doi.org/10.1083/jcb.200501113

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