Table of Contents Author Guidelines Submit a Manuscript
Journal of Diabetes Research
Volume 2016 (2016), Article ID 2391592, 14 pages
http://dx.doi.org/10.1155/2016/2391592
Research Article

An Investigation into the Antiobesity Effects of Morinda citrifolia L. Leaf Extract in High Fat Diet Induced Obese Rats Using a 1H NMR Metabolomics Approach

1Faculty of Food Science and Technology, Universiti Putra Malaysia, 43400 Serdang, Selangor, Malaysia
2Faculty of Medicine and Health Sciences, Universiti Putra Malaysia, 43400 Serdang, Selangor, Malaysia
3Department of Pharmaceutical Chemistry, Kulliyyah of Pharmacy, International Islamic University Malaysia, 25200 Kuantan, Pahang, Malaysia
4Department of Health Sciences, Faculty of Science, University of Mauritius, 230 Réduit, Mauritius
5Halal Products Research Institute, Universiti Putra Malaysia, 43400 Serdang, Selangor, Malaysia

Received 14 June 2015; Revised 13 September 2015; Accepted 13 September 2015

Academic Editor: Michal Ciborowski

Copyright © 2016 Najla Gooda Sahib Jambocus et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Linked References

  1. J. W. Yun, “Possible anti-obesity therapeutics from nature—a review,” Phytochemistry, vol. 71, no. 14-15, pp. 1625–1641, 2010. View at Publisher · View at Google Scholar · View at Scopus
  2. A. G. Dulloo, C. Duret, D. Rohrer et al., “Efficacy of a green tea extract rich in catechin polyphenols and caffeine in increasing 24-h energy expenditure and fat oxidation in humans,” The American Journal of Clinical Nutrition, vol. 70, no. 6, pp. 1040–1045, 1999. View at Google Scholar · View at Scopus
  3. P. Chantre and D. Lairon, “Recent findings of green tea extract AR25 (Exolise) and its activity for the treatment of obesity,” Phytomedicine, vol. 9, no. 1, pp. 3–8, 2002. View at Publisher · View at Google Scholar · View at Scopus
  4. C. Lu, W. Zhu, C.-L. Shen, and W. Gao, “Green tea polyphenols reduce body weight in rats by modulating obesity-related genes,” PLoS ONE, vol. 7, no. 6, Article ID e38332, 2012. View at Publisher · View at Google Scholar · View at Scopus
  5. L.-K. Han, Y. Kimura, and H. Okuda, “Reduction in fat storage during chitin-chitosan treatment in mice fed a high-fat diet,” International Journal of Obesity, vol. 23, no. 2, pp. 174–179, 1999. View at Publisher · View at Google Scholar · View at Scopus
  6. M. Yamamoto, S. Shimura, Y. Itoh, T. Ohsaka, M. Egawa, and S. Inoue, “Anti-obesity effects of lipase inhibitor CT-II, an extract from edible herbs, Nomame Herba, on rats fed a high-fat diet,” International Journal of Obesity, vol. 24, no. 6, pp. 758–764, 2000. View at Publisher · View at Google Scholar · View at Scopus
  7. A. M. M. Jalil, A. Ismail, P. P. Chong, M. Hamid, and S. H. S. Kamaruddin, “Effects of cocoa extract containing polyphenols and methylxanthines on biochemical parameters of obese-diabetic rats,” Journal of the Science of Food and Agriculture, vol. 89, no. 1, pp. 130–137, 2009. View at Publisher · View at Google Scholar · View at Scopus
  8. J. B. German, B. D. Hammock, and S. M. Watkins, “Metabolomics: building on a century of biochemistry to guide human health,” Metabolomics, vol. 1, no. 1, pp. 3–9, 2005. View at Publisher · View at Google Scholar
  9. M. Wang, R.-J. A. N. Lamers, H. A. A. J. Korthout et al., “Metabolomics in the context of systems biology: bridging traditional Chinese medicine and molecular pharmacology,” Phytotherapy Research, vol. 19, no. 3, pp. 173–182, 2005. View at Publisher · View at Google Scholar · View at Scopus
  10. B. Wu, S. Yan, Z. Lin et al., “Metabonomic study on ageing: NMR-based investigation into rat urinary metabolites and the effect of the total flavone of Epimedium,” Molecular BioSystems, vol. 4, no. 8, pp. 855–861, 2008. View at Publisher · View at Google Scholar · View at Scopus
  11. K. S. Solanky, N. J. C. Bailey, B. M. Beckwith-Hall et al., “Application of biofluid 1H nuclear magnetic resonance-based metabonomic techniques for the analysis of the biochemical effects of dietary isoflavones on human plasma profile,” Analytical Biochemistry, vol. 323, no. 2, pp. 197–204, 2003. View at Publisher · View at Google Scholar · View at Scopus
  12. O. Beckonert, H. C. Keun, T. M. D. Ebbels et al., “Metabolic profiling, metabolomic and metabonomic procedures for NMR spectroscopy of urine, plasma, serum and tissue extracts,” Nature protocols, vol. 2, no. 11, pp. 2692–2703, 2007. View at Publisher · View at Google Scholar · View at Scopus
  13. S.-H. Kim, S.-O. Yang, H.-S. Kim, Y. Kim, T. Park, and H.-K. Choi, “1H-nuclear magnetic resonance spectroscopy-based metabolic assessment in a rat model of obesity induced by a high-fat diet,” Analytical and Bioanalytical Chemistry, vol. 395, no. 4, pp. 1117–1124, 2009. View at Publisher · View at Google Scholar · View at Scopus
  14. G. E. Duggan, D. S. Hittel, C. C. Hughey, A. Weljie, H. J. Vogel, and J. Shearer, “Differentiating short- and long-term effects of diet in the obese mouse using 1H-nuclear magnetic resonance metabolomics,” Diabetes, Obesity and Metabolism, vol. 13, no. 9, pp. 859–862, 2011. View at Publisher · View at Google Scholar · View at Scopus
  15. E.-Y. Won, M.-K. Yoon, S.-W. Kim et al., “Gender specific metabolomic profiling of obesity in leptin deficient ob/ob mice by 1H NMR spectroscopy,” PLoS ONE, vol. 8, no. 10, Article ID e75998, 2013. View at Publisher · View at Google Scholar · View at Scopus
  16. X. Song, J. Wang, P. Wang, N. Tian, M. Yang, and L. Kong, “1H NMR-based metabolomics approach to evaluate the effect of Xue-Fu-Zhu-Yu decoction on hyperlipidemia rats induced by high-fat diet,” Journal of Pharmaceutical and Biomedical Analysis, vol. 78-79, pp. 202–210, 2013. View at Publisher · View at Google Scholar · View at Scopus
  17. J. Gerlach, “Native or introduced plant species,” Phelsuma, vol. 4, pp. 70–74, 1996. View at Google Scholar
  18. A. R. Dixon, H. McMillen, and N. L. Etkin, “Ferment this: the transformation of Noni, a traditional Polynesian medicine (Morinda citrifolia, Rubiaceae),” Economic Botany, vol. 53, no. 1, pp. 51–68, 1999. View at Publisher · View at Google Scholar
  19. S.-U. R. Mandukhail, N. Aziz, and A.-H. Gilani, “Studies on antidyslipidemic effects of Morinda citrifolia (Noni) fruit, leaves and root extracts,” Lipids in Health and Disease, vol. 9, article 88, 2010. View at Publisher · View at Google Scholar · View at Scopus
  20. M. S. Pak-Dek, A. Abdul-Hamid, A. Osman, and C. S. Soh, “Inhibitory effect of Morinda citrifolia L. on lipoprotein lipase activity,” Journal of Food Science, vol. 73, no. 8, pp. C595–C598, 2008. View at Publisher · View at Google Scholar · View at Scopus
  21. N. G. Sahib, A. A. Hamid, D. Kitts, M. Purnama, N. Saari, and F. Abas, “The effects of Morinda citrifolia, Momordica charantia and Centella asiatica extracts on lipoprotein lipase and 3T3-L1 preadipocytes,” Journal of Food Biochemistry, vol. 35, no. 4, pp. 1186–1205, 2011. View at Publisher · View at Google Scholar · View at Scopus
  22. N. Gooda Sahib, A. Abdul Hamid, N. Saari, F. Abas, M. S. Pak Dek, and M. Rahim, “Anti-pancreatic lipase and antioxidant activity of selected tropical herbs,” International Journal of Food Properties, vol. 15, no. 3, pp. 569–578, 2012. View at Publisher · View at Google Scholar · View at Scopus
  23. T. Tsujita, H. Takaichi, T. Takaku, S. Aoyama, and J. Hiraki, “Antiobesity action of epsilon-polylysine, a potent inhibitor of pancreatic lipase,” Journal of Lipid Research, vol. 47, no. 8, pp. 1852–1858, 2006. View at Publisher · View at Google Scholar · View at Scopus
  24. L. Ericksson, E. Johansson, N. Kettanen-Wold, J. Trygg, C. Wikstrom, and S. Wold, Multi- and Megavariate Data Analysis, Part 1. Basic Principles & Applications, Umetrics Academy, Umea, Sweden, 2006.
  25. V. Von Diemen, E. N. Trindade, and M. R. M. Trindade, “Experimental model to induce obesity in rats,” Acta Cirurgica Brasileira, vol. 21, no. 6, pp. 425–429, 2006. View at Google Scholar · View at Scopus
  26. S. C. Woods, R. J. Seeley, P. A. Rushing, D. D'Alessio, and P. Tso, “A controlled high-fat diet induces an obese syndrome in rats,” Journal of Nutrition, vol. 133, no. 4, pp. 1081–1087, 2003. View at Google Scholar · View at Scopus
  27. R. Buettner, J. Schölmerich, and L. C. Bollheimer, “High-fat diets: modeling the metabolic disorders of human obesity in rodents,” Obesity, vol. 15, no. 4, pp. 798–808, 2007. View at Publisher · View at Google Scholar · View at Scopus
  28. P. Yaqoob, E. J. Sherrington, N. M. Jeffery et al., “Comparison of the effects of a range of dietary lipids upon serum and tissue lipid composition in the rat,” The International Journal of Biochemistry and Cell Biology, vol. 27, no. 3, pp. 297–310, 1995. View at Publisher · View at Google Scholar · View at Scopus
  29. J.-S. Tian, B.-Y. Shi, H. Xiang, S. Gao, X.-M. Qin, and G.-H. Du, “1H-NMR-based metabonomic studies on the anti-depressant effect of genipin in the chronic unpredictable mild stress rat model,” PLoS ONE, vol. 8, no. 9, Article ID e75721, 2013. View at Publisher · View at Google Scholar · View at Scopus
  30. N. Tian, J. Wang, P. Wang, X. Song, M. Yang, and L. Kong, “NMR-based metabonomic study of Chinese medicine Gegen Qinlian Decoction as an effective treatment for type 2 diabetes in rats,” Metabolomics, vol. 9, no. 6, pp. 1228–1242, 2013. View at Publisher · View at Google Scholar · View at Scopus
  31. S. Bouatra, F. Aziat, R. Mandal et al., “The human urine metabolome,” PLoS ONE, vol. 8, no. 9, Article ID e73076, 2013. View at Publisher · View at Google Scholar · View at Scopus
  32. N. Psychogios, D. D. Hau, J. Peng et al., “The human serum metabolome,” PLoS ONE, vol. 6, no. 2, Article ID e16957, 2011. View at Publisher · View at Google Scholar
  33. N. J. Serkova, M. Jackman, J. L. Brown et al., “Metabolic profiling of livers and blood from obese Zucker rats,” Journal of Hepatology, vol. 44, no. 5, pp. 956–962, 2006. View at Publisher · View at Google Scholar · View at Scopus
  34. A. Waldram, E. Holmes, Y. Wang et al., “Top-down systems biology modeling of host metabotype-microbiome associations in obese rodents,” Journal of Proteome Research, vol. 8, no. 5, pp. 2361–2375, 2009. View at Publisher · View at Google Scholar · View at Scopus
  35. L.-C. Zhao, X.-D. Zhang, S.-X. Liao, H.-Y. Wang, D.-H. Lin, and H.-C. Gao, “A metabonomic comparison of urinary changes in Zucker and GK rats,” Journal of Biomedicine and Biotechnology, vol. 2010, Article ID 431894, 6 pages, 2010. View at Publisher · View at Google Scholar · View at Scopus
  36. A. A. Mahdi, S. Annarao, S. Tripathi et al., “Correlation of age related metabonomic changes in 1H NMR serum and urine profiles of rats with cognitive function,” The Open Magnetic Resonance Journal, vol. 1, no. 1, pp. 71–76, 2008. View at Publisher · View at Google Scholar
  37. H. J. Schirra, C. G. Anderson, W. J. Wilson et al., “Altered metabolism of growth hormone receptor mutant mice: a combined NMR metabonomics and microarray study,” PLoS ONE, vol. 3, no. 7, Article ID e2764, 2008. View at Publisher · View at Google Scholar · View at Scopus
  38. J. Shearer, G. Duggan, A. Weljie, D. S. Hittel, D. H. Wasserman, and H. J. Vogel, “Metabolomic profiling of dietary-induced insulin resistance in the high fat-fed C57BL/6J mouse,” Diabetes, Obesity and Metabolism, vol. 10, no. 10, pp. 950–958, 2008. View at Publisher · View at Google Scholar · View at Scopus
  39. H. Li, Z. Xie, J. Lin et al., “Transcriptomic and metabonomic profiling of obesity-prone and obesity-resistant rats under high fat diet,” Journal of Proteome Research, vol. 7, no. 11, pp. 4775–4783, 2008. View at Publisher · View at Google Scholar · View at Scopus
  40. D. C. DeVilliers, P. K. Dixit, and A. Lazarow, “Citrate metabolism in diabetes. I. Plasma citrate in alloxan-diabetic rats and in clinical diabetes,” Metabolism, vol. 15, no. 5, pp. 458–465, 1966. View at Publisher · View at Google Scholar · View at Scopus
  41. A. Cupisti, M. Meola, C. D'Alessandro et al., “Insulin resistance and low urinary citrate excretion in calcium stone formers,” Biomedicine & Pharmacotherapy, vol. 61, no. 1, pp. 86–90, 2007. View at Publisher · View at Google Scholar · View at Scopus
  42. G. Souto, C. Donapetry, J. Calviño, and M. M. Adeva, “Metabolic acidosis-induced insulin resistance and cardiovascular risk,” Metabolic Syndrome and Related Disorders, vol. 9, no. 4, pp. 247–253, 2011. View at Publisher · View at Google Scholar · View at Scopus
  43. B. Xie, M. J. Waters, and H. J. Schirra, “Investigating potential mechanisms of obesity by metabolomics,” Journal of Biomedicine and Biotechnology, vol. 2012, Article ID 805683, 10 pages, 2012. View at Publisher · View at Google Scholar · View at Scopus
  44. M. Piccinini, M. Mostert, G. Alberto et al., “Down-regulation of pyruvate dehydrogenase phosphatase in obese subjects is a defect that signals insulin resistance,” Obesity Research, vol. 13, no. 4, pp. 678–686, 2005. View at Publisher · View at Google Scholar · View at Scopus
  45. Q. He, P. Ren, X. Kong et al., “Comparison of serum metabolite compositions between obese and lean growing pigs using an NMR-based metabonomic approach,” Journal of Nutritional Biochemistry, vol. 23, no. 2, pp. 133–139, 2012. View at Publisher · View at Google Scholar · View at Scopus
  46. H. Satoh, “Cardioprotective actions of taurine against intracellular and extracellular calcium-induced effects,” Advances in Experimental Medicine and Biology, vol. 359, pp. 181–196, 1994. View at Publisher · View at Google Scholar · View at Scopus
  47. Y. Nakaya, A. Minami, N. Harada, S. Sakamoto, Y. Niwa, and M. Ohnaka, “Taurine improves insulin sensitivity in the Otsuka Long-Evans Tokushima Fatty rat, a model of spontaneous type 2 diabetes,” American Journal of Clinical Nutrition, vol. 71, no. 1, pp. 54–58, 2000. View at Google Scholar · View at Scopus
  48. N. Tsuboyama-Kasaoka, C. Shozawa, K. Sano et al., “Taurine (2-aminoethanesulfonic acid) deficiency creates a vicious circle promoting obesity,” Endocrinology, vol. 147, no. 7, pp. 3276–3284, 2006. View at Publisher · View at Google Scholar · View at Scopus
  49. M. Lever and S. Slow, “The clinical significance of betaine, an osmolyte with a key role in methyl group metabolism,” Clinical Biochemistry, vol. 43, no. 9, pp. 732–744, 2010. View at Publisher · View at Google Scholar · View at Scopus
  50. J. Pekkinen, K. Olli, A. Huotari et al., “Betaine supplementation causes increase in carnitine metabolites in the muscle and liver of mice fed a high-fat diet as studied by nontargeted LC-MS metabolomics approach,” Molecular Nutrition & Food Research, vol. 57, no. 11, pp. 1959–1968, 2013. View at Publisher · View at Google Scholar · View at Scopus
  51. M. S. Klein, C. Dorn, M. Saugspier, C. Hellerbrand, P. J. Oefner, and W. Gronwald, “Discrimination of steatosis and NASH in mice using nuclear magnetic resonance spectroscopy,” Metabolomics, vol. 7, no. 2, pp. 237–246, 2011. View at Publisher · View at Google Scholar · View at Scopus
  52. J. B. Walker, “Metabolic control of creatine biosynthesis. II. Restoration of transamidinase activity following creatine repression,” The Journal of Biological Chemistry, vol. 236, pp. 493–498, 1961. View at Google Scholar · View at Scopus
  53. S. R. Kimball and L. S. Jefferson, “Regulation of protein synthesis by branched-chain amino acids,” Current Opinion in Clinical Nutrition and Metabolic Care, vol. 4, no. 1, pp. 39–43, 2001. View at Publisher · View at Google Scholar · View at Scopus
  54. J. K. Nicholson, E. Holmes, and I. D. Wilson, “Gut microorganisms, mammalian metabolism and personalized health care,” Nature Reviews Microbiology, vol. 3, no. 5, pp. 431–438, 2005. View at Publisher · View at Google Scholar · View at Scopus
  55. A. N. Phipps, J. Stewart, B. Wright, and I. D. Wilson, “Effect of diet on the urinary excretion of hippuric acid and other dietary-derived aromatics in rat. A complex interaction between diet, gut microflora and substrate specificity,” Xenobiotica, vol. 28, no. 5, pp. 527–537, 1998. View at Publisher · View at Google Scholar · View at Scopus
  56. E.-Y. Won, M.-K. Yoon, S.-W. Kim et al., “Gender specific metabolomic profiling of obesity in leptin deficient ob/ob mice by 1H NMR spectroscopy,” PLoS ONE, vol. 8, no. 10, Article ID e75998, 2013. View at Publisher · View at Google Scholar · View at Scopus
  57. S. Rezzi, Z. Ramadan, F.-P. J. Martin et al., “Human metabolic phenotypes link directly to specific dietary preferences in healthy individuals,” Journal of Proteome Research, vol. 6, no. 11, pp. 4469–4477, 2007. View at Publisher · View at Google Scholar · View at Scopus
  58. J. Sun, L. K. Schnackenberg, R. D. Holland et al., “Metabonomics evaluation of urine from rats given acute and chronic doses of acetaminophen using NMR and UPLC/MS,” Journal of Chromatography B, vol. 871, no. 2, pp. 328–340, 2008. View at Publisher · View at Google Scholar · View at Scopus
  59. R. Calvani, A. Miccheli, G. Capuani et al., “Gut microbiome-derived metabolites characterize a peculiar obese urinary metabotype,” International Journal of Obesity, vol. 34, no. 6, pp. 1095–1098, 2010. View at Publisher · View at Google Scholar · View at Scopus
  60. C. B. Newgard, J. An, J. R. Bain et al., “A branched chain amino acid-related metabolic signature that differentiates obese and lean humans and contributes to insulin resistance,” Cell Metabolism, vol. 9, no. 4, pp. 311–326, 2009. View at Publisher · View at Google Scholar · View at Scopus
  61. R. A. Kreisberg, “Glucose-lactate inter-relations in man,” The New England Journal of Medicine, vol. 287, no. 3, pp. 132–137, 1972. View at Publisher · View at Google Scholar · View at Scopus
  62. P.-A. Jansson, A. Larsson, U. Smith, and P. Lönnroth, “Lactate release from the subcutaneous tissue in lean and obese men,” The Journal of Clinical Investigation, vol. 93, no. 1, pp. 240–246, 1994. View at Publisher · View at Google Scholar · View at Scopus
  63. J. Aduen, W. K. Bernstein, T. Khastagir et al., “The use and clinical importance of a substrate-specific electrode for rapid determination of blood lactate concentrations,” The Journal of the American Medical Association, vol. 272, no. 21, pp. 1678–1685, 2004. View at Publisher · View at Google Scholar
  64. J. Lovejoy, F. D. Newby, S. S. P. Gebhart, and M. DiGirolamo, “Insulin resistance in obesity is associated with elevated basal lactate levels and diminished lactate appearance following intravenous glucose and insulin,” Metabolism, vol. 41, no. 1, pp. 22–27, 1992. View at Publisher · View at Google Scholar · View at Scopus
  65. Y. D. I. Chen, B. B. Varasteh, and G. M. Reaven, “Plasma lactate concentration in obesity and type 2 diabetes,” Diabete et Metabolisme, vol. 19, no. 4, pp. 348–354, 1993. View at Google Scholar · View at Scopus
  66. N. Friedrich, K. Budde, T. Wolf et al., “Short-term changes of the urine metabolome after bariatric surgery,” OMICS, vol. 16, no. 11, pp. 612–620, 2012. View at Publisher · View at Google Scholar · View at Scopus
  67. G. L. S. Pawan and S. J. G. Semple, “Effect of 3-hydroxybutyrate in obese subjects on very-low-energy diets and during therapeutic starvation,” The Lancet, vol. 321, no. 8314-8315, pp. 15–17, 1983. View at Publisher · View at Google Scholar · View at Scopus
  68. R. Nosadini, A. Avogaro, and R. Trevisan, “Acetoacetate and 3-hydroxybutyrate kinetics in obese and insulin-dependent diabetic humans,” The American Journal of Physiology—Regulatory Integrative and Comparative Physiology, vol. 248, no. 5, part 2, pp. R611–R620, 1985. View at Google Scholar · View at Scopus
  69. J. S. Fisler, M. Egawa, and G. A. Bray, “Peripheral 3-hydroxybutyrate and food intake in a model of dietary-fat induced obesity: effect of vagotomy,” Physiology & Behavior, vol. 58, no. 1, pp. 1–7, 1995. View at Publisher · View at Google Scholar · View at Scopus
  70. N. Gooda Sahib, N. Saari, A. Ismail, A. Khatib, F. Mahomoodally, and A. Abdul Hamid, “Plants' metabolites as potential antiobesity agents,” The Scientific World Journal, vol. 2012, Article ID 436039, 8 pages, 2012. View at Publisher · View at Google Scholar · View at Scopus
  71. A. Perez-Cornago, L. Brennan, I. Ibero-Baraibar et al., “Metabolomics identifies changes in fatty acid and amino acid profiles in serum of overweight older adults following a weight loss intervention,” Journal of Physiology and Biochemistry, vol. 70, no. 2, pp. 593–602, 2014. View at Publisher · View at Google Scholar · View at Scopus
  72. S. Wahl, C. Holzapfel, Z. Yu et al., “Metabolomics reveals determinants of weight loss during lifestyle intervention in obese children,” Metabolomics, vol. 9, no. 6, pp. 1157–1167, 2013. View at Publisher · View at Google Scholar · View at Scopus
  73. P. S. Larmo, A. J. Kangas, P. Soininen et al., “Effects of sea buckthorn and bilberry on serum metabolites differ according to baseline metabolic profiles in overweight women: a randomized crossover trial,” The American Journal of Clinical Nutrition, vol. 98, no. 4, pp. 941–951, 2013. View at Publisher · View at Google Scholar · View at Scopus
  74. M. J. Kim, H. J. Yang, J. H. Kim et al., “Obesity-related metabolomic analysis of human subjects in black soybean peptide intervention study by ultraperformance liquid chromatography and quadrupole-time-of-flight mass spectrometry,” Journal of Obesity, vol. 2013, Article ID 874981, 11 pages, 2013. View at Publisher · View at Google Scholar · View at Scopus
  75. J. M. Miles, L. Leiter, P. Hollander et al., “Effect of orlistat in overweight and obese patients with type 2 diabetes treated with metformin,” Diabetes Care, vol. 25, no. 7, pp. 1123–1128, 2002. View at Publisher · View at Google Scholar · View at Scopus
  76. J. S. Torgerson, J. Hauptman, M. N. Boldrin, and L. Sjöström, “Xenical in the prevention of diabetes in obese subjects (XENDOS) study: a randomized study of orlistat as an adjunct to lifestyle changes for the prevention of type 2 diabetes in obese patients,” Diabetes Care, vol. 27, no. 1, pp. 155–161, 2004. View at Publisher · View at Google Scholar · View at Scopus
  77. H. M. Sickmann, H. S. Waagepetersen, A. Schousboe, A. J. Benie, and S. D. Bouman, “Obesity and type 2 diabetes in rats are associated with altered brain glycogen and amino-acid homeostasis,” Journal of Cerebral Blood Flow & Metabolism, vol. 30, no. 8, pp. 1527–1537, 2010. View at Publisher · View at Google Scholar · View at Scopus
  78. S. Satapati, N. E. Sunny, B. Kucejova et al., “Elevated TCA cycle function in the pathology of diet-induced hepatic insulin resistance and fatty liver,” Journal of Lipid Research, vol. 53, no. 6, pp. 1080–1092, 2012. View at Publisher · View at Google Scholar · View at Scopus
  79. I. H. De Boer, S. D. Sibley, B. Kestenbaum et al., “Central obesity, incident microalbuminuria, and change in creatinine clearance in the epidemiology of diabetes interventions and complications study,” Journal of the American Society of Nephrology, vol. 18, no. 1, pp. 235–243, 2007. View at Publisher · View at Google Scholar · View at Scopus
  80. D. S. Hittel, Y. Hathout, E. P. Huffman, and J. A. Houmard, “Proteome analysis of skeletal muscle from obese and morbidly obese women,” Diabetes, vol. 54, no. 5, pp. 1283–1288, 2005. View at Publisher · View at Google Scholar · View at Scopus