Table of Contents Author Guidelines Submit a Manuscript
PPAR Research
Volume 2016, Article ID 4794576, 17 pages
http://dx.doi.org/10.1155/2016/4794576
Review Article

Nutrigenomic Functions of PPARs in Obesogenic Environments

1Department of Nutrition and Health Sciences, University of Nebraska-Lincoln, Lincoln, NE, USA
2Department of Food & Biotechnology, Korea University, Sejong, Republic of Korea
3Department of Food and Nutrition, Seoul Women’s University, Seoul, Republic of Korea
4Department of Food Science and Nutrition, Jeju National University, Jeju, Republic of Korea
5Department of Food and Nutrition and Research Institute of Obesity Science, Sungshin Women’s University, Seoul, Republic of Korea

Received 26 July 2016; Accepted 3 October 2016

Academic Editor: John P. Vanden Heuvel

Copyright © 2016 Soonkyu Chung 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. R. M. Evans, G. D. Barish, and Y.-X. Wang, “PPARs and the complex journey to obesity,” Nature Medicine, vol. 10, no. 4, pp. 355–361, 2004. View at Publisher · View at Google Scholar · View at Scopus
  2. M. Ahmadian, J. M. Suh, N. Hah et al., “PPARγ signaling and metabolism: the good, the bad and the future,” Nature Medicine, vol. 19, no. 5, pp. 557–566, 2013. View at Publisher · View at Google Scholar · View at Scopus
  3. F. A. Monsalve, R. D. Pyarasani, F. Delgado-Lopez, and R. Moore-Carrasco, “Peroxisome proliferator-activated receptor targets for the treatment of metabolic diseases,” Mediators of Inflammation, vol. 2013, Article ID 549627, 18 pages, 2013. View at Publisher · View at Google Scholar · View at Scopus
  4. P. Tontonoz and B. M. Spiegelman, “Fat and beyond: the diverse biology of PPARγ,” Annual Review of Biochemistry, vol. 77, pp. 289–312, 2008. View at Publisher · View at Google Scholar · View at Scopus
  5. J. Yan, Y. Zhao, and B. Zhao, “Green tea catechins prevent obesity through modulation of peroxisome proliferator-activated receptors,” Science China Life Sciences, vol. 56, no. 9, pp. 804–810, 2013. View at Publisher · View at Google Scholar · View at Scopus
  6. D. W. Shin, S. N. Kim, S. M. Lee et al., “(−)-Catechin promotes adipocyte differentiation in human bone marrow mesenchymal stem cells through PPARγ transactivation,” Biochemical Pharmacology, vol. 77, no. 1, pp. 125–133, 2009. View at Publisher · View at Google Scholar · View at Scopus
  7. Y. Sakamoto, A. Naka, N. Ohara, K. Kondo, and K. Iida, “Daidzein regulates proinflammatory adipokines thereby improving obesity-related inflammation through PPARγ,” Molecular Nutrition and Food Research, vol. 58, no. 4, pp. 718–726, 2014. View at Publisher · View at Google Scholar · View at Scopus
  8. K. W. Cho, O.-H. Lee, W. J. Banz, N. Moustaid-Moussa, N. F. Shay, and Y.-C. Kim, “Daidzein and the daidzein metabolite, equol, enhance adipocyte differentiation and PPARγ transcriptional activity,” The Journal of Nutritional Biochemistry, vol. 21, no. 9, pp. 841–847, 2010. View at Publisher · View at Google Scholar · View at Scopus
  9. K. Morikawa, C. Ikeda, M. Nonaka et al., “Epigallocatechin gallate-induced apoptosis does not affect adipocyte conversion of preadipocytes,” Cell Biology International, vol. 31, no. 11, pp. 1379–1387, 2007. View at Publisher · View at Google Scholar · View at Scopus
  10. T. Jin, O. Y. Kim, M.-J. Shin et al., “Fisetin up-regulates the expression of adiponectin in 3t3-L1 adipocytes via the activation of silent mating type information regulation 2 homologue 1 (SIRT1)-deacetylase and peroxisome proliferator-activated receptors (PPARs),” Journal of Agricultural and Food Chemistry, vol. 62, no. 43, pp. 10468–10474, 2014. View at Publisher · View at Google Scholar · View at Scopus
  11. T. Saito, D. Abe, and K. Sekiya, “Flavanone exhibits PPARγ ligand activity and enhances differentiation of 3T3-L1 adipocytes,” Biochemical and Biophysical Research Communications, vol. 380, no. 2, pp. 281–285, 2009. View at Publisher · View at Google Scholar · View at Scopus
  12. K. Gamo, H. Miyachi, K. Nakamura, and N. Matsuura, “Hesperetin glucuronides induce adipocyte differentiation via activation and expression of peroxisome proliferator-activated receptor-γ,” Bioscience, Biotechnology, and Biochemistry, vol. 78, no. 6, pp. 1052–1059, 2014. View at Publisher · View at Google Scholar · View at Scopus
  13. Q. Sun and G. Chou, “Isoflavonoids from Crotalaria albida inhibit adipocyte differentiation and lipid accumulation in 3T3-L1 cells via suppression of PPAR-γ pathway,” PLoS ONE, vol. 10, no. 8, Article ID e0135893, 2015. View at Publisher · View at Google Scholar · View at Scopus
  14. X.-K. Fang, J. Gao, and D.-N. Zhu, “Kaempferol and quercetin isolated from Euonymus alatus improve glucose uptake of 3T3-L1 cells without adipogenesis activity,” Life Sciences, vol. 82, no. 11-12, pp. 615–622, 2008. View at Publisher · View at Google Scholar · View at Scopus
  15. H.-Y. Quan, N. I. Baek, and S. H. Chung, “Licochalcone a prevents adipocyte differentiation and lipogenesis via suppression of peroxisome proliferator-activated receptor γ and sterol regulatory element-binding protein pathways,” Journal of Agricultural and Food Chemistry, vol. 60, no. 20, pp. 5112–5120, 2012. View at Publisher · View at Google Scholar · View at Scopus
  16. H.-S. Park, S.-H. Kim, Y. S. Kim et al., “Luteolin inhibits adipogenic differentiation by regulating PPARc activation,” BioFactors, vol. 35, no. 4, pp. 373–379, 2009. View at Publisher · View at Google Scholar · View at Scopus
  17. L. Chen, T. He, Y. Han et al., “Pentamethylquercetin improves adiponectin expression in differentiated 3T3-L1 cells via a mechanism that implicates PPARγ together with TNF-α and IL-6,” Molecules, vol. 16, no. 7, pp. 5754–5768, 2011. View at Google Scholar
  18. S. Wein, N. Behm, R. K. Petersen, K. Kristiansen, and S. Wolffram, “Quercetin enhances adiponectin secretion by a PPAR-γ independent mechanism,” European Journal of Pharmaceutical Sciences, vol. 41, no. 1, pp. 16–22, 2010. View at Publisher · View at Google Scholar · View at Scopus
  19. L. Yang, X.-F. Li, L. Gao, Y.-O. Zhang, and G.-P. Cai, “Suppressive effects of quercetin-3-O-(6-feruloyl)-β-D- galactopyranoside on adipogenesis in 3T3-L1 preadipocytes through down-regulation of PPARγ and C/EBPα expression,” Phytotherapy Research, vol. 26, no. 3, pp. 438–444, 2012. View at Publisher · View at Google Scholar · View at Scopus
  20. T. Saito, D. Abe, and K. Sekiya, “Sakuranetin induces adipogenesis of 3T3-L1 cells through enhanced expression of PPARγ2,” Biochemical and Biophysical Research Communications, vol. 372, no. 4, pp. 835–839, 2008. View at Publisher · View at Google Scholar · View at Scopus
  21. Y. F. He, F. Y. Liu, and W. X. Zhang, “Tangeritin inhibits adipogenesis by down-regulating C/EBPα, C/EBPβ, and PPARγ expression in 3T3-L1 fat cells,” Genetics and Molecular Research, vol. 14, no. 4, pp. 13642–13648, 2015. View at Publisher · View at Google Scholar · View at Scopus
  22. R. Siersbæk, R. Nielsen, and S. Mandrup, “Transcriptional networks and chromatin remodeling controlling adipogenesis,” Trends in Endocrinology & Metabolism, vol. 23, no. 2, pp. 56–64, 2012. View at Publisher · View at Google Scholar · View at Scopus
  23. D. J. Steger, G. R. Grant, M. Schupp et al., “Propagation of adipogenic signals through an epigenomic transition state,” Genes & Development, vol. 24, no. 10, pp. 1035–1044, 2010. View at Publisher · View at Google Scholar · View at Scopus
  24. R. M. Cowherd, R. E. Lyle, and R. E. McGehee Jr., “Molecular regulation of adipocyte differentiation,” Seminars in Cell and Developmental Biology, vol. 10, no. 1, pp. 3–10, 1999. View at Publisher · View at Google Scholar · View at Scopus
  25. E. D. Rosen, P. Sarraf, A. E. Troy et al., “PPARγ is required for the differentiation of adipose tissue in vivo and in vitro,” Molecular Cell, vol. 4, no. 4, pp. 611–617, 1999. View at Publisher · View at Google Scholar · View at Scopus
  26. Z. Wu, E. D. Rosen, R. Brun et al., “Cross-regulation of C/EBPα and PPARγ controls the transcriptional pathway of adipogenesis and insulin sensitivity,” Molecular Cell, vol. 3, no. 2, pp. 151–158, 1999. View at Publisher · View at Google Scholar · View at Scopus
  27. R. P. Brun, P. Tontonoz, B. M. Forman et al., “Differential activation of adipogenesis by multiple PPAR isoforms,” Genes and Development, vol. 10, no. 8, pp. 974–984, 1996. View at Publisher · View at Google Scholar · View at Scopus
  28. P. Tontonoz, E. Hu, and B. M. Spiegelman, “Stimulation of adipogenesis in fibroblasts by PPARγ2, a lipid-activated transcription factor,” Cell, vol. 79, no. 7, pp. 1147–1156, 1994. View at Publisher · View at Google Scholar · View at Scopus
  29. Y. Barak, M. C. Nelson, E. S. Ong et al., “PPARγ is required for placental, cardiac, and adipose tissue development,” Molecular Cell, vol. 4, no. 4, pp. 585–595, 1999. View at Publisher · View at Google Scholar · View at Scopus
  30. S. F. Schmidt, M. Jørgensen, Y. Chen, R. Nielsen, A. Sandelin, and S. Mandrup, “Cross species comparison of C/EBPα and PPARγ profiles in mouse and human adipocytes reveals interdependent retention of binding sites,” BMC Genomics, vol. 12, article 152, 2011. View at Publisher · View at Google Scholar · View at Scopus
  31. M. S. Madsen, R. Siersbæk, M. Boergesen, R. Nielsen, and S. Mandrup, “Peroxisome proliferator-activated receptor γ and C/EBPα synergistically activate key metabolic adipocyte genes by assisted loading,” Molecular and Cellular Biology, vol. 34, no. 6, pp. 939–954, 2014. View at Publisher · View at Google Scholar · View at Scopus
  32. W. Tang, D. Zeve, J. Seo, A.-Y. Jo, and J. M. Graff, “Thiazolidinediones regulate adipose lineage dynamics,” Cell Metabolism, vol. 14, no. 1, pp. 116–122, 2011. View at Publisher · View at Google Scholar · View at Scopus
  33. W. Tang, D. Zeve, J. M. Suh et al., “White fat progenitor cells reside in the adipose vasculature,” Science, vol. 322, no. 5901, pp. 583–586, 2008. View at Publisher · View at Google Scholar · View at Scopus
  34. T. Imai, R. Takakuwa, S. Marchand et al., “Peroxisome proliferator-activated receptor γ is required in mature white and brown adipocytes for their survival in the mouse,” Proceedings of the National Academy of Sciences of the United States of America, vol. 101, no. 13, pp. 4543–4547, 2004. View at Publisher · View at Google Scholar · View at Scopus
  35. K. Tomita, Y. Oike, T. Teratani et al., “Hepatic AdipoR2 signaling plays a protective role against progression of nonalcoholic steatohepatitis in mice,” Hepatology, vol. 48, no. 2, pp. 458–473, 2008. View at Publisher · View at Google Scholar · View at Scopus
  36. A. Tsuchida, T. Yamauchi, S. Takekawa et al., “Peroxisome proliferator-activated receptor (PPAR)α activation increases adiponectin receptors and reduces obesity-related inflammation in adipose tissue: comparison of activation of PPARα, PPARγ, and their combination,” Diabetes, vol. 54, no. 12, pp. 3358–3370, 2005. View at Google Scholar
  37. A. N. Hollenberg, V. S. Susulic, J. P. Madura et al., “Functional antagonism between CCAAT/enhancer binding protein-α and peroxisome proliferator-activated receptor-γ on the leptin promoter,” Journal of Biological Chemistry, vol. 272, no. 8, pp. 5283–5290, 1997. View at Publisher · View at Google Scholar · View at Scopus
  38. J. W. Jonker, J. M. Suh, A. R. Atkins et al., “A PPARγ-FGF1 axis is required for adaptive adipose remodelling and metabolic homeostasis,” Nature, vol. 485, no. 7398, pp. 391–394, 2012. View at Publisher · View at Google Scholar · View at Scopus
  39. T. Coskun, H. A. Bina, M. A. Schneider et al., “Fibroblast growth factor 21 corrects obesity in mice,” Endocrinology, vol. 149, no. 12, pp. 6018–6027, 2008. View at Publisher · View at Google Scholar · View at Scopus
  40. P. A. Dutchak, T. Katafuchi, A. L. Bookout et al., “Fibroblast growth factor-21 regulates PPARγ activity and the antidiabetic actions of thiazolidinediones,” Cell, vol. 148, no. 3, pp. 556–567, 2012. View at Publisher · View at Google Scholar · View at Scopus
  41. T. Tomaru, D. J. Steger, M. I. Lefterova, M. Schupp, and M. A. Lazar, “Adipocyte-specific expression of murine resistin is mediated by synergism between peroxisome proliferator-activated receptor γ and CCAAT/enhancer-binding proteins,” Journal of Biological Chemistry, vol. 284, no. 10, pp. 6116–6125, 2009. View at Publisher · View at Google Scholar · View at Scopus
  42. Y. Hou, F. Moreau, and K. Chadee, “PPARγ is an E3 ligase that induces the degradation of NFκB/p65,” Nature Communications, vol. 3, article 1300, 2012. View at Publisher · View at Google Scholar · View at Scopus
  43. J. Ye, “Regulation of PPARγ function by TNF-α,” Biochemical and Biophysical Research Communications, vol. 374, no. 3, pp. 405–408, 2008. View at Publisher · View at Google Scholar · View at Scopus
  44. A. Okuno, H. Tamemoto, K. Tobe et al., “Troglitazone increases the number of small adipocytes without the change of white adipose tissue mass in obese Zucker rats,” Journal of Clinical Investigation, vol. 101, no. 6, pp. 1354–1361, 1998. View at Publisher · View at Google Scholar · View at Scopus
  45. P. Arner, “The adipocyte in insulin resistance: key molecules and the impact of the thiazolidinediones,” Trends in Endocrinology and Metabolism, vol. 14, no. 3, pp. 137–145, 2003. View at Publisher · View at Google Scholar · View at Scopus
  46. P. G. Blanchard, V. Turcotte, M. Cote et al., “Peroxisome proliferator-activated receptor γ activation favours selective subcutaneous lipid deposition by coordinately regulating lipoprotein lipase modulators, fatty acid transporters and lipogenic enzymes,” Acta Physiologica, vol. 217, no. 3, pp. 227–239, 2016. View at Publisher · View at Google Scholar
  47. M. Laplante, W. T. Festuccia, G. Soucy et al., “Tissue-specific postprandial clearance is the major determinant of PPARγ-induced triglyceride lowering in the rat,” American Journal of Physiology—Regulatory Integrative and Comparative Physiology, vol. 296, no. 1, pp. R57–R66, 2009. View at Publisher · View at Google Scholar · View at Scopus
  48. S. Chatterjee, A. Majumder, and S. Ray, “Observational study of effects of saroglitazar on glycaemic and lipid parameters on indian patients with type 2 diabetes,” Scientific Reports, vol. 5, article 7706, 2015. View at Publisher · View at Google Scholar · View at Scopus
  49. R. H. Jani, V. Pai, P. Jha et al., “A multicenter, prospective, randomized, double-blind study to evaluate the safety and efficacy of Saroglitazar 2 and 4 mg compared with placebo in type 2 diabetes mellitus patients having hypertriglyceridemia not controlled with atorvastatin therapy (PRESS VI),” Diabetes Technology & Therapeutics, vol. 16, no. 2, pp. 63–71, 2014. View at Publisher · View at Google Scholar · View at Scopus
  50. S. G. Kim, D. M. Kim, J.-T. Woo et al., “Efficacy and safety of lobeglitazone monotherapy in patients with type 2 diabetes mellitus over 24-weeks: a multicenter, randomized, double-blind, parallel-group, placebo controlled trial,” PLoS ONE, vol. 9, no. 4, Article ID e92843, 2014. View at Publisher · View at Google Scholar · View at Scopus
  51. S. H. Kim, S. G. Kim, D. M. Kim et al., “Safety and efficacy of lobeglitazone monotherapy in patients with type 2 diabetes mellitus over 52 weeks: an open-label extension study,” Diabetes Research and Clinical Practice, vol. 110, no. 3, pp. e27–e30, 2015. View at Publisher · View at Google Scholar · View at Scopus
  52. J. Wu, P. Boström, L. M. Sparks et al., “Beige adipocytes are a distinct type of thermogenic fat cell in mouse and human,” Cell, vol. 150, no. 2, pp. 366–376, 2012. View at Publisher · View at Google Scholar · View at Scopus
  53. B. B. Lowell and B. M. Spiegelman, “Towards a molecular understanding of adaptive thermogenesis,” Nature, vol. 404, no. 6778, pp. 652–660, 2000. View at Google Scholar · View at Scopus
  54. A. M. Cypess, A. P. White, C. Vernochet et al., “Anatomical localization, gene expression profiling and functional characterization of adult human neck brown fat,” Nature Medicine, vol. 19, no. 5, pp. 635–639, 2013. View at Publisher · View at Google Scholar · View at Scopus
  55. P. Seale, B. Bjork, W. Yang et al., “PRDM16 controls a brown fat/skeletal muscle switch,” Nature, vol. 454, no. 7207, pp. 961–967, 2008. View at Publisher · View at Google Scholar · View at Scopus
  56. P. Seale, S. Kajimura, W. Yang et al., “Transcriptional control of brown fat determination by PRDM16,” Cell Metabolism, vol. 6, no. 1, pp. 38–54, 2007. View at Publisher · View at Google Scholar · View at Scopus
  57. M. Rosenwald, A. Perdikari, T. Rülicke, and C. Wolfrum, “Bi-directional interconversion of brite and white adipocytes,” Nature Cell Biology, vol. 15, no. 6, pp. 659–667, 2013. View at Publisher · View at Google Scholar · View at Scopus
  58. M. Rosenwald and C. Wolfrum, “The origin and definition of brite versus white and classical brown adipocytes,” Adipocyte, vol. 3, no. 1, pp. 4–9, 2014. View at Publisher · View at Google Scholar
  59. L. Z. Sharp, K. Shinoda, H. Ohno et al., “Human BAT possesses molecular signatures that resemble beige/brite cells,” PLoS ONE, vol. 7, no. 11, Article ID e49452, 2012. View at Publisher · View at Google Scholar · View at Scopus
  60. W. D. Van Marken Lichtenbelt, J. W. Vanhommerig, N. M. Smulders et al., “Cold-activated brown adipose tissue in healthy men,” The New England Journal of Medicine, vol. 360, no. 15, pp. 1500–1508, 2009. View at Publisher · View at Google Scholar · View at Scopus
  61. L. Ye, J. Wu, P. Cohen et al., “Fat cells directly sense temperature to activate thermogenesis,” Proceedings of the National Academy of Sciences of the United States of America, vol. 110, no. 30, pp. 12480–12485, 2013. View at Publisher · View at Google Scholar · View at Scopus
  62. B. K. Pedersen and M. A. Febbraio, “Muscles, exercise and obesity: skeletal muscle as a secretory organ,” Nature Reviews Endocrinology, vol. 8, no. 8, pp. 457–465, 2012. View at Publisher · View at Google Scholar · View at Scopus
  63. I. B. Sears, M. A. MacGinnitie, L. G. Kovacs, and R. A. Graves, “Differentiation-dependent expression of the brown adipocyte uncoupling protein gene: regulation by peroxisome proliferator-activated receptor gamma,” Molecular and Cellular Biology, vol. 16, no. 7, pp. 3410–3419, 1996. View at Publisher · View at Google Scholar · View at Scopus
  64. S. L. Gray, E. Dalla Nora, E. C. Backlund et al., “Decreased brown adipocyte recruitment and thermogenic capacity in mice with impaired peroxisome proliferator-activated receptor (P465L PPARγ) function,” Endocrinology, vol. 147, no. 12, pp. 5708–5714, 2006. View at Publisher · View at Google Scholar · View at Scopus
  65. S. Rajakumari, J. Wu, J. Ishibashi et al., “EBF2 determines and maintains brown adipocyte identity,” Cell Metabolism, vol. 17, no. 4, pp. 562–574, 2013. View at Publisher · View at Google Scholar · View at Scopus
  66. M. S. Siersbæk, A. Loft, M. M. Aagaard et al., “Genome-wide profiling of peroxisome proliferator-activated receptor γ in primary epididymal, inguinal, and brown adipocytes reveals depot-selective binding correlated with gene expression,” Molecular and Cellular Biology, vol. 32, no. 17, pp. 3452–3463, 2012. View at Publisher · View at Google Scholar · View at Scopus
  67. S. Bartesaghi, S. Hallen, L. Huang et al., “Thermogenic activity of UCP1 in human white fat-derived beige adipocytes,” Molecular Endocrinology, vol. 29, no. 1, pp. 130–139, 2015. View at Publisher · View at Google Scholar · View at Scopus
  68. L. Wilson-Fritch, A. Burkart, G. Bell et al., “Mitochondrial biogenesis and remodeling during adipogenesis and in response to the insulin sensitizer rosiglitazone,” Molecular and Cellular Biology, vol. 23, no. 3, pp. 1085–1094, 2003. View at Publisher · View at Google Scholar · View at Scopus
  69. L. Wilson-Fritch, S. Nicoloro, M. Chouinard et al., “Mitochondrial remodeling in adipose tissue associated with obesity and treatment with rosiglitazone,” Journal of Clinical Investigation, vol. 114, no. 9, pp. 1281–1289, 2004. View at Publisher · View at Google Scholar · View at Scopus
  70. J. X. Rong, Y. Qiu, M. K. Hansen et al., “Adipose mitochondrial biogenesis is suppressed in db/db and high-fat diet-fed mice and improved by rosiglitazone,” Diabetes, vol. 56, no. 7, pp. 1751–1760, 2007. View at Publisher · View at Google Scholar · View at Scopus
  71. N. Petrovic, I. G. Shabalina, J. A. Timmons, B. Cannon, and J. Nedergaard, “Thermogenically competent nonadrenergic recruitment in brown preadipocytes by a PPARγ agonist,” American Journal of Physiology: Endocrinology and Metabolism, vol. 295, no. 2, pp. E287–E296, 2008. View at Publisher · View at Google Scholar · View at Scopus
  72. N. Petrovic, T. B. Walden, I. G. Shabalina, J. A. Timmons, B. Cannon, and J. Nedergaard, “Chronic peroxisome proliferator-activated receptor γ (PPARγ) activation of epididymally derived white adipocyte cultures reveals a population of thermogenically competent, UCP1-containing adipocytes molecularly distinct from classic brown adipocytes,” The Journal of Biological Chemistry, vol. 285, no. 10, pp. 7153–7164, 2010. View at Publisher · View at Google Scholar · View at Scopus
  73. Y. Fukui, S.-I. Masui, S. Osada, K. Umesono, and K. Motojima, “A new thiazolidinedione, NC-2100, which is a weak PPAR-γ activator, exhibits potent antidiabetic effects and induces uncoupling protein 1 in white adipose tissue of KKAy obese mice,” Diabetes, vol. 49, no. 5, pp. 759–767, 2000. View at Publisher · View at Google Scholar · View at Scopus
  74. H. Ohno, K. Shinoda, B. M. Spiegelman, and S. Kajimura, “PPARγ agonists induce a white-to-brown fat conversion through stabilization of PRDM16 protein,” Cell Metabolism, vol. 15, no. 3, pp. 395–404, 2012. View at Publisher · View at Google Scholar · View at Scopus
  75. W. T. Festuccia, P.-G. Blanchard, V. Turcotte et al., “The PPARγ agonist rosiglitazone enhances rat brown adipose tissue lipogenesis from glucose without altering glucose uptake,” American Journal of Physiology—Regulatory Integrative and Comparative Physiology, vol. 296, no. 5, pp. R1327–R1335, 2009. View at Publisher · View at Google Scholar · View at Scopus
  76. W. T. Festuccia, S. Oztezcan, M. Laplante et al., “Peroxisome proliferator-activated receptor-γ-mediated positive energy balance in the rat is associated with reduced sympathetic drive to adipose tissues and thyroid status,” Endocrinology, vol. 149, no. 5, pp. 2121–2130, 2008. View at Publisher · View at Google Scholar · View at Scopus
  77. E. Bakopanos and J. E. Silva, “Thiazolidinediones inhibit the expression of β3-adrenergic receptors at a transcriptional level,” Diabetes, vol. 49, no. 12, pp. 2108–2115, 2000. View at Publisher · View at Google Scholar · View at Scopus
  78. L. Qiang, L. Wang, N. Kon et al., “Brown remodeling of white adipose tissue by SirT1-dependent deacetylation of Pparγ,” Cell, vol. 150, no. 3, pp. 620–632, 2012. View at Publisher · View at Google Scholar · View at Scopus
  79. T. L. Rachid, A. Penna-de-Carvalho, I. Bringhenti, M. B. Aguila, C. A. Mandarim-de-Lacerda, and V. Souza-Mello, “Fenofibrate (PPARalpha agonist) induces beige cell formation in subcutaneous white adipose tissue from diet-induced male obese mice,” Molecular and Cellular Endocrinology, vol. 402, pp. 86–94, 2015. View at Publisher · View at Google Scholar · View at Scopus
  80. P. Boström, J. Wu, M. P. Jedrychowski et al., “A PGC1-α-dependent myokine that drives brown-fat-like development of white fat and thermogenesis,” Nature, vol. 481, no. 7382, pp. 463–468, 2012. View at Publisher · View at Google Scholar · View at Scopus
  81. A. Fredenrich and P. A. Grimaldi, “PPAR delta: an uncompletely known nuclear receptor,” Diabetes and Metabolism, vol. 31, no. 1, pp. 23–27, 2005. View at Publisher · View at Google Scholar · View at Scopus
  82. Q. A. Wang and P. E. Scherer, “The AdipoChaser mouse: a model tracking adipogenesis in vivo,” Adipocyte, vol. 3, no. 2, pp. 146–150, 2014. View at Publisher · View at Google Scholar
  83. Q. A. Wang, C. Tao, R. K. Gupta, and P. E. Scherer, “Tracking adipogenesis during white adipose tissue development, expansion and regeneration,” Nature Medicine, vol. 19, no. 10, pp. 1338–1344, 2013. View at Publisher · View at Google Scholar · View at Scopus
  84. J. R. Brestoff, B. S. Kim, S. A. Saenz et al., “Group 2 innate lymphoid cells promote beiging of white adipose tissue and limit obesity,” Nature, vol. 519, no. 7542, pp. 242–246, 2015. View at Publisher · View at Google Scholar · View at Scopus
  85. M.-W. Lee, J. I. Odegaard, L. Mukundan et al., “Activated type 2 innate lymphoid cells regulate beige fat biogenesis,” Cell, vol. 160, no. 1-2, pp. 74–87, 2015. View at Publisher · View at Google Scholar · View at Scopus
  86. K. D. Nguyen, Y. Qiu, X. Cui et al., “Alternatively activated macrophages produce catecholamines to sustain adaptive thermogenesis,” Nature, vol. 480, no. 7375, pp. 104–108, 2011. View at Publisher · View at Google Scholar · View at Scopus
  87. Y. Qiu, K. D. Nguyen, J. I. Odegaard et al., “Eosinophils and type 2 cytokine signaling in macrophages orchestrate development of functional beige fat,” Cell, vol. 157, no. 6, pp. 1292–1308, 2014. View at Publisher · View at Google Scholar · View at Scopus
  88. A. Bartelt, O. T. Bruns, R. Reimer et al., “Brown adipose tissue activity controls triglyceride clearance,” Nature Medicine, vol. 17, no. 2, pp. 200–205, 2011. View at Publisher · View at Google Scholar · View at Scopus
  89. P. A. Kern, B. S. Finlin, B. Zhu et al., “The effects of temperature and seasons on subcutaneous white adipose tissue in humans: evidence for thermogenic gene induction,” The Journal of Clinical Endocrinology & Metabolism, vol. 99, no. 12, pp. E2772–E2779, 2014. View at Publisher · View at Google Scholar · View at Scopus
  90. M. Matsushita, T. Yoneshiro, S. Aita, T. Kameya, H. Sugie, and M. Saito, “Impact of brown adipose tissue on body fatness and glucose metabolism in healthy humans,” International Journal of Obesity, vol. 38, no. 6, pp. 812–817, 2014. View at Publisher · View at Google Scholar · View at Scopus
  91. T. Yoneshiro, S. Aita, M. Matsushita et al., “Age-related decrease in cold-activated brown adipose tissue and accumulation of body fat in healthy humans,” Obesity, vol. 19, no. 9, pp. 1755–1760, 2011. View at Publisher · View at Google Scholar · View at Scopus
  92. J. Bae, J. Chen, and L. Zhao, “Chronic activation of pattern recognition receptors suppresses brown adipogenesis of multipotent mesodermal stem cells and brown pre-adipocytes,” Biochemistry and Cell Biology, vol. 93, no. 3, pp. 251–261, 2015. View at Publisher · View at Google Scholar · View at Scopus
  93. M. d. Ibarra-Lara, M. Sánchez-Aguilar, E. Soria et al., “Peroxisome proliferator-activated receptors (PPAR) downregulate the expression of pro-inflammatory molecules in an experimental model of myocardial infarction,” Canadian Journal of Physiology and Pharmacology, vol. 94, no. 6, pp. 634–642, 2016. View at Publisher · View at Google Scholar
  94. E. L. Schiffrin and P. Paradis, “Suppression of peroxisome proliferator-activated receptor-γ activity by angiotensin II in vascular smooth muscle involves Bcr kinase: the fire that drowns the water,” Circulation Research, vol. 104, no. 1, pp. 4–6, 2009. View at Publisher · View at Google Scholar · View at Scopus
  95. A. H. V. Remels, R. C. J. Langen, H. R. Gosker et al., “PPARγ inhibits NF-κB-dependent transcriptional activation in skeletal muscle,” American Journal of Physiology—Endocrinology and Metabolism, vol. 297, no. 1, pp. E174–E183, 2009. View at Publisher · View at Google Scholar · View at Scopus
  96. M. Okla, W. Wang, I. Kang, A. Pashaj, T. Carr, and S. Chung, “Activation of Toll-like receptor 4 (TLR4) attenuates adaptive thermogenesis via endoplasmic reticulum stress,” The Journal of Biological Chemistry, vol. 290, no. 44, pp. 26476–26490, 2015. View at Publisher · View at Google Scholar · View at Scopus
  97. T. Goto, S. Naknukool, R. Yoshitake et al., “Proinflammatory cytokine interleukin-1β suppresses cold-induced thermogenesis in adipocytes,” Cytokine, vol. 77, pp. 107–114, 2016. View at Publisher · View at Google Scholar · View at Scopus
  98. S. Hirai, N. Takahashi, T. Goto et al., “Functional food targeting the regulation of obesity-induced inflammatory responses and pathologies,” Mediators of Inflammation, vol. 2010, Article ID 367838, 8 pages, 2010. View at Publisher · View at Google Scholar · View at Scopus
  99. T. Varga, Z. Czimmerer, and L. Nagy, “PPARs are a unique set of fatty acid regulated transcription factors controlling both lipid metabolism and inflammation,” Biochimica et Biophysica Acta (BBA)—Molecular Basis of Disease, vol. 1812, no. 8, pp. 1007–1022, 2011. View at Publisher · View at Google Scholar · View at Scopus
  100. H. Martin, “Role of PPAR-gamma in inflammation. Prospects for therapeutic intervention by food components,” Mutation Research, vol. 669, no. 1-2, pp. 1–7, 2009. View at Publisher · View at Google Scholar · View at Scopus
  101. B. M. Forman, J. Chen, and R. M. Evans, “Hypolipidemic drugs, polyunsaturated fatty acids, and eicosanoids are ligands for peroxisome proliferator-activated receptors α and δ,” Proceedings of the National Academy of Sciences of the United States of America, vol. 94, no. 9, pp. 4312–4317, 1997. View at Publisher · View at Google Scholar · View at Scopus
  102. S. A. Kliewer, S. S. Sundseth, S. A. Jones et al., “Fatty acids and eicosanoids regulate gene expression through direct interactions with peroxisome proliferator-activated receptors α and γ,” Proceedings of the National Academy of Sciences of the United States of America, vol. 94, no. 9, pp. 4318–4323, 1997. View at Publisher · View at Google Scholar · View at Scopus
  103. V. R. Narala, R. K. Adapala, M. V. Suresh, T. G. Brock, M. Peters-Golden, and R. C. Reddy, “Leukotriene B4 is a physiologically relevant endogenous peroxisome proliferator-activated receptor-α agonist,” Journal of Biological Chemistry, vol. 285, no. 29, pp. 22067–22074, 2010. View at Publisher · View at Google Scholar · View at Scopus
  104. G. Krey, O. Braissant, F. L'Horset et al., “Fatty acids, eicosanoids, and hypolipidemic agents identified as ligands of peroxisome proliferator-activated receptors by coactivator-dependent receptor ligand assay,” Molecular Endocrinology, vol. 11, no. 6, pp. 779–791, 1997. View at Publisher · View at Google Scholar · View at Scopus
  105. G. M. Reaven and A. Laws, “Insulin resistance, compensatory hyperinsulinaemia, and coronary heart disease,” Diabetologia, vol. 37, no. 9, pp. 948–952, 1994. View at Publisher · View at Google Scholar · View at Scopus
  106. M. Y. Abeywardena and R. J. Head, “Longchain n-3 polyunsaturated fatty acids and blood vessel function,” Cardiovascular Research, vol. 52, no. 3, pp. 361–371, 2001. View at Publisher · View at Google Scholar · View at Scopus
  107. R. De Caterina and A. Zampolli, “n-3 fatty acids: antiatherosclerotic effects,” Lipids, vol. 36, supplement, pp. S69–S78, 2001. View at Publisher · View at Google Scholar · View at Scopus
  108. S. A. Khan and J. P. Vanden Heuvel, “Role of nuclear receptors in the regulation of gene expression by dietary fatty acids,” The Journal of Nutritional Biochemistry, vol. 14, no. 10, pp. 554–567, 2003. View at Publisher · View at Google Scholar · View at Scopus
  109. G. Schmitz and J. Ecker, “The opposing effects of n-3 and n-6 fatty acids,” Progress in Lipid Research, vol. 47, no. 2, pp. 147–155, 2008. View at Publisher · View at Google Scholar · View at Scopus
  110. J. R. Marszalek and H. F. Lodish, “Docosahexaenoic acid, fatty acid-interacting proteins, and neuronal function: breastmilk and fish are good for you,” Annual Review of Cell and Developmental Biology, vol. 21, pp. 633–657, 2005. View at Publisher · View at Google Scholar · View at Scopus
  111. W. Wahli and L. Michalik, “PPARs at the crossroads of lipid signaling and inflammation,” Trends in Endocrinology and Metabolism, vol. 23, no. 7, pp. 351–363, 2012. View at Publisher · View at Google Scholar · View at Scopus
  112. C. Couet, J. Delarue, P. Ritz et al., “Effect of dietary fish oil on body fat mass and basal fat oxidation in healthy adults,” International Journal of Obesity and Related Metabolic Disorders, vol. 21, no. 8, pp. 637–643, 1997. View at Publisher · View at Google Scholar
  113. T. A. Mori, D. Q. Bao, V. Burke, I. B. Puddey, G. F. Watts, and L. J. Beilin, “Dietary fish as a major component of a weight-loss diet: effect on serum lipids, glucose, and insulin metabolism in overweight hypertensive subjects,” American Journal of Clinical Nutrition, vol. 70, no. 5, pp. 817–825, 1999. View at Google Scholar · View at Scopus
  114. G. W. Power and E. A. Newsholme, “Dietary fatty acids influence the activity and metabolic control of mitochondrial carnitine palmitoyltransferase I in rat heart and skeletal muscle,” Journal of Nutrition, vol. 127, no. 11, pp. 2142–2150, 1997. View at Google Scholar · View at Scopus
  115. P. R. Devchand, H. Keller, J. M. Peters, M. Vazquez, F. J. Gonzalez, and W. Wahli, “The PPARα-leukotriene B4 pathway to inflammation control,” Nature, vol. 384, no. 6604, pp. 39–43, 1996. View at Publisher · View at Google Scholar · View at Scopus
  116. K. Yu, W. Bayona, C. B. Kallen et al., “Differential activation of peroxisome proliferator-activated receptors by eicosanoids,” The Journal of Biological Chemistry, vol. 270, no. 41, pp. 23975–23983, 1995. View at Publisher · View at Google Scholar · View at Scopus
  117. F. Borrelli and A. A. Izzo, “Role of acylethanolamides in the gastrointestinal tract with special reference to food intake and energy balance,” Best Practice and Research: Clinical Endocrinology and Metabolism, vol. 23, no. 1, pp. 33–49, 2009. View at Publisher · View at Google Scholar · View at Scopus
  118. S. E. O'Sullivan, “Cannabinoids go nuclear: evidence for activation of peroxisome proliferator-activated receptors,” British Journal of Pharmacology, vol. 152, no. 5, pp. 576–582, 2007. View at Publisher · View at Google Scholar · View at Scopus
  119. T. Waku, T. Shiraki, T. Oyama et al., “Structural insight into PPARγ activation through covalent modification with endogenous fatty acids,” Journal of Molecular Biology, vol. 385, no. 1, pp. 188–199, 2009. View at Publisher · View at Google Scholar · View at Scopus
  120. J. Huber, M. Löffler, M. Bilban et al., “Prevention of high-fat diet-induced adipose tissue remodeling in obese diabetic mice by n-3 polyunsaturated fatty acids,” International Journal of Obesity, vol. 31, no. 6, pp. 1004–1013, 2007. View at Publisher · View at Google Scholar · View at Scopus
  121. J. Todoric, M. Löffler, J. Huber et al., “Adipose tissue inflammation induced by high-fat diet in obese diabetic mice is prevented by n-3 polyunsaturated fatty acids,” Diabetologia, vol. 49, no. 9, pp. 2109–2119, 2006. View at Publisher · View at Google Scholar · View at Scopus
  122. M. W. Pariza and Y. L. Ha, “Conjugated dienoic derivatives of linoleic acid: a new class of anticarcinogens,” Medical Oncology and Tumor Pharmacotherapy, vol. 7, no. 2-3, pp. 169–171, 1990. View at Google Scholar · View at Scopus
  123. Y. Park, K. J. Albright, W. Liu, J. M. Storkson, M. E. Cook, and M. W. Pariza, “Effect of conjugated linoleic acid on body composition in mice,” Lipids, vol. 32, no. 8, pp. 853–858, 1997. View at Publisher · View at Google Scholar · View at Scopus
  124. Y. Park, J. M. Storkson, K. J. Albright, W. Liu, and M. W. Pariza, “Evidence that the trans-10,cis-12 isomer of conjugated linoleic acid induces body composition changes in mice,” Lipids, vol. 34, no. 3, pp. 235–241, 1999. View at Publisher · View at Google Scholar · View at Scopus
  125. S. Y. Moya-Camarena, J. P. Vanden Heuvel, S. G. Blanchard, L. A. Leesnitzer, and M. A. Belury, “Conjugated linoleic acid is a potent naturally occurring ligand and activator of PPARα,” Journal of Lipid Research, vol. 40, no. 8, pp. 1426–1433, 1999. View at Google Scholar · View at Scopus
  126. Y. Yu, P. H. Correll, and J. P. Vanden Heuvel, “Conjugated linoleic acid decreases production of pro-inflammatory products in macrophages: evidence for a PPARγ-dependent mechanism,” Biochimica et Biophysica Acta (BBA)—Molecular and Cell Biology of Lipids, vol. 1581, no. 3, pp. 89–99, 2002. View at Publisher · View at Google Scholar · View at Scopus
  127. A. Truitt, G. McNeill, and J. Y. Vanderhoek, “Antiplatelet effects of conjugated linoleic acid isomers,” Biochimica et Biophysica Acta—Molecular and Cell Biology of Lipids, vol. 1438, no. 2, pp. 239–246, 1999. View at Publisher · View at Google Scholar · View at Scopus
  128. C. Ip, Y. Dong, H. J. Thompson, D. E. Bauman, and M. M. Ip, “Control of rat mammary epithelium proliferation by conjugated linoleic acid,” Nutrition and Cancer, vol. 39, no. 2, pp. 233–238, 2001. View at Publisher · View at Google Scholar · View at Scopus
  129. A. Kennedy, S. Chung, K. LaPoint, O. Fabiyi, and M. K. McIntosh, “Trans-10, cis-12 conjugated linoleic acid antagonizes ligand-dependent PPARγ activity in primary cultures of human adipocytes,” Journal of Nutrition, vol. 138, no. 3, pp. 455–461, 2008. View at Google Scholar · View at Scopus
  130. D. B. Jump, “Dietary polyunsaturated fatty acids and regulation of gene transcription,” Current Opinion in Lipidology, vol. 13, no. 2, pp. 155–164, 2002. View at Publisher · View at Google Scholar · View at Scopus
  131. D. B. Jump and S. D. Clarke, “Regulation of gene expression by dietary fat,” Annual Review of Nutrition, vol. 19, pp. 63–90, 1999. View at Publisher · View at Google Scholar · View at Scopus
  132. M. A. Zulet, A. Marti, M. D. Parra, and J. A. Martínez, “Inflammation and conjugated linoleic acid: mechanisms of action and implications for human health,” Journal of Physiology and Biochemistry, vol. 61, no. 3, pp. 483–494, 2005. View at Publisher · View at Google Scholar · View at Scopus
  133. C. E. Loscher, E. Draper, O. Leavy, D. Kelleher, K. H. G. Mills, and H. M. Roche, “Conjugated linoleic acid suppresses NF-kappa B activation and IL-12 production in dendritic cells through ERK-mediated IL-10 induction,” The Journal of Immunology, vol. 175, no. 8, pp. 4990–4998, 2005. View at Google Scholar · View at Scopus
  134. M. Luongo, B. Knotek, and L. Biel, “Peritoneal dialysis nurse resource guide,” Nephrology Nursing Journal, vol. 30, no. 5, pp. 535–564, 2003. View at Google Scholar · View at Scopus
  135. B. Winkel-Shirley, “Flavonoid biosynthesis. A colorful model for genetics, biochemistry, cell biology, and biotechnology,” Plant Physiology, vol. 126, no. 2, pp. 485–493, 2001. View at Publisher · View at Google Scholar · View at Scopus
  136. M. Ferrali, C. Signorini, B. Caciotti et al., “Protection against oxidative damage of erythrocyte membrane by the flavonoid quercetin and its relation to iron chelating activity,” FEBS Letters, vol. 416, no. 2, pp. 123–129, 1997. View at Publisher · View at Google Scholar · View at Scopus
  137. L. G. Korkina and I. B. Afanas'ev, “Antioxidant and chelating properties of flavonoids,” Advances in Pharmacology, vol. 38, pp. 151–163, 1996. View at Publisher · View at Google Scholar · View at Scopus
  138. R. Hirano, W. Sasamoto, A. Matsumoto, H. Itakura, O. Igarashi, and K. Kondo, “Antioxidant ability of various flavonoids against DPPH radicals and LDL oxidation,” Journal of Nutritional Science and Vitaminology, vol. 47, no. 5, pp. 357–362, 2001. View at Publisher · View at Google Scholar · View at Scopus
  139. A. J. Elliott, S. A. Scheiber, C. Thomas, and R. S. Pardini, “Inhibition of glutathione reductase by flavonoids. A structure-activity study,” Biochemical Pharmacology, vol. 44, no. 8, pp. 1603–1608, 1992. View at Publisher · View at Google Scholar · View at Scopus
  140. K. E. Heim, A. R. Tagliaferro, and D. J. Bobilya, “Flavonoid antioxidants: chemistry, metabolism and structure-activity relationships,” Journal of Nutritional Biochemistry, vol. 13, no. 10, pp. 572–584, 2002. View at Publisher · View at Google Scholar · View at Scopus
  141. J. Sastre, F. V. Pallardö, and J. Viña, “Mitochondrial oxidative stress plays a key role in aging and apoptosis,” IUBMB Life, vol. 49, no. 5, pp. 427–435, 2000. View at Publisher · View at Google Scholar · View at Scopus
  142. W. Takabe, E. Niki, K. Uchida, S. Yamada, K. Satoh, and N. Noguchi, “Oxidative stress promotes the development of transformation: Involvement of a potent mutagenic lipid peroxidation product, acrolein,” Carcinogenesis, vol. 22, no. 6, pp. 935–941, 2001. View at Publisher · View at Google Scholar · View at Scopus
  143. S. Kawanishi, Y. Hiraku, and S. Oikawa, “Mechanism of guanine-specific DNA damage by oxidative stress and its role in carcinogenesis and aging,” Mutation Research, vol. 488, no. 1, pp. 65–76, 2001. View at Publisher · View at Google Scholar · View at Scopus
  144. K. Kondo, R. Hirano, A. Matsumoto, O. Igarashi, and H. Itakura, “Inhibition of LDL oxidation by cocoa,” The Lancet, vol. 348, no. 9040, p. 1514, 1996. View at Google Scholar · View at Scopus
  145. A. Mazur, D. Bayle, C. Lab, E. Rock, and Y. Rayssiguier, “Inhibitory effect of procyanidin-rich extracts on LDL oxidation in vitro,” Atherosclerosis, vol. 145, no. 2, pp. 421–422, 1999. View at Publisher · View at Google Scholar · View at Scopus
  146. M. A. Khan and A. Baseer, “Increased malondialdehyde levels in coronary heart disease,” Journal of the Pakistan Medical Association, vol. 50, no. 8, pp. 261–264, 2000. View at Google Scholar · View at Scopus
  147. R. M. Facino, M. Carini, G. Aldini et al., “Diet enriched with procyanidins enhances antioxidant activity and reduces myocardial post-ischaemic damage in rats,” Life Sciences, vol. 64, no. 8, pp. 627–642, 1999. View at Publisher · View at Google Scholar · View at Scopus
  148. 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
  149. S. Wang, S. K. Noh, and S. I. Koo, “Green tea catechins inhibit pancreatic phospholipase A2 and intestinal absorption of lipids in ovariectomized rats,” The Journal of Nutritional Biochemistry, vol. 17, no. 7, pp. 492–498, 2006. View at Publisher · View at Google Scholar · View at Scopus
  150. 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,” American Journal of Clinical Nutrition, vol. 70, no. 6, pp. 1040–1045, 1999. View at Google Scholar · View at Scopus
  151. M. L. Bertoia, E. B. Rimm, K. J. Mukamal et al., “Dietary flavonoid intake and weight maintenance: three prospective cohorts of 124,086 US men and women followed for up to 24 years,” BMJ, vol. 352, article i17, 2016. View at Google Scholar
  152. E. D. Rosen, C.-H. Hsu, X. Wang et al., “C/EBPα induces adipogenesis through PPARγ: a unified pathway,” Genes and Development, vol. 16, no. 1, pp. 22–26, 2002. View at Publisher · View at Google Scholar · View at Scopus
  153. R. M. Lago, P. P. Singh, and R. W. Nesto, “Congestive heart failure and cardiovascular death in patients with prediabetes and type 2 diabetes given thiazolidinediones: a meta-analysis of randomised clinical trials,” The Lancet, vol. 370, no. 9593, pp. 1129–1136, 2007. View at Publisher · View at Google Scholar · View at Scopus
  154. S. Mudaliar, A. R. Chang, and R. R. Henry, “Thiazolidinediones, peripheral edema, and type 2 diabetes: incidence, pathophysiology, and clinical implications,” Endocrine Practice, vol. 9, no. 5, pp. 406–416, 2003. View at Publisher · View at Google Scholar · View at Scopus
  155. R. W. Nesto, D. Bell, R. O. Bonow et al., “Thiazolidinedione use, fluid retention, and congestive heart failure: a consensus statement from the American Heart Association and American Diabetes Association,” Diabetes Care, vol. 27, no. 1, pp. 256–263, 2004. View at Publisher · View at Google Scholar · View at Scopus
  156. C. Weidner, J. C. de Groot, A. Prasad et al., “Amorfrutins are potent antidiabetic dietary natural products,” Proceedings of the National Academy of Sciences of the United States of America, vol. 109, no. 19, pp. 7257–7262, 2012. View at Publisher · View at Google Scholar · View at Scopus
  157. L. Wang, B. Waltenberger, E.-M. Pferschy-Wenzig et al., “Natural product agonists of peroxisome proliferator-activated receptor gamma (PPARγ): a review,” Biochemical Pharmacology, vol. 92, no. 1, pp. 73–89, 2014. View at Publisher · View at Google Scholar · View at Scopus
  158. Y. Zhang, L. Yu, W. Cai et al., “Protopanaxatriol, a novel PPAR γ antagonist from Panax ginseng, alleviates steatosis in mice,” Scientific Reports, vol. 4, article 7375, 2014. View at Publisher · View at Google Scholar · View at Scopus
  159. R. H. Houtkooper and J. Auwerx, “Obesity: new life for antidiabetic drugs,” Nature, vol. 466, no. 7305, pp. 443–444, 2010. View at Publisher · View at Google Scholar · View at Scopus
  160. A. V. Contreras, N. Torres, and A. R. Tovar, “PPAR-α as a key nutritional and environmental sensor for metabolic adaptation,” Advances in Nutrition, vol. 4, no. 4, pp. 439–452, 2013. View at Publisher · View at Google Scholar · View at Scopus
  161. R. Stienstra, C. Duval, M. Müller, and S. Kersten, “PPARs, obesity, and inflammation,” PPAR Research, vol. 2007, Article ID 95974, 10 pages, 2007. View at Publisher · View at Google Scholar · View at Scopus
  162. W. He, “Polymorphism and human health,” PPAR Research, vol. 2009, Article ID 849538, 15 pages, 2009. View at Publisher · View at Google Scholar
  163. I. Barroso, M. Gurnell, V. E. F. Crowley et al., “Dominant negative mutations in human PPARγ associated with severe insulin resistance, diabetes mellitus and hypertension,” Nature, vol. 402, no. 6764, pp. 880–883, 1999. View at Publisher · View at Google Scholar · View at Scopus
  164. M. Laakso, “Mutations in PPARr gene relevant for the diabetes and the metabolic syndrome,” in Nutritional Genomics: Impact on Health and Disease, H. G. J. R. Brigelius-Flohe, Ed., pp. 195–205, Wiley-VCH, New York, NY, USA, 2006. View at Google Scholar
  165. M. Ristow, D. Müller-Wieland, A. Pfeiffer, W. Krone, and C. R. Kahn, “Obesity associated with a mutation in a genetic regulator of adipocyte differentiation,” The New England Journal of Medicine, vol. 339, no. 14, pp. 953–959, 1998. View at Publisher · View at Google Scholar · View at Scopus
  166. M. Stumvoll and H. Häring, “The peroxisome proliferator-activated receptor-γ2 Pro12Ala polymorphism,” Diabetes, vol. 51, no. 8, pp. 2341–2347, 2002. View at Publisher · View at Google Scholar · View at Scopus
  167. D. Altshuler, J. N. Hirschhorn, M. Klannemark et al., “The common PPARγ Pro12Ala polymorphism is associated with decreased risk of type 2 diabetes,” Nature Genetics, vol. 26, no. 1, pp. 76–80, 2000. View at Publisher · View at Google Scholar · View at Scopus
  168. V. Radha, K. S. Vimaleswaran, H. N. S. Babu et al., “Role of genetic polymorphism peroxisome proliferator-activated receptor-γ2 Pro12Ala on ethnic susceptibility to diabetes in South-Asian and Caucasian subjects: evidence for heterogeneity,” Diabetes Care, vol. 29, no. 5, pp. 1046–1051, 2006. View at Publisher · View at Google Scholar · View at Scopus
  169. E. S. Tai, D. Corella, M. Deurenberg-Yap et al., “Differential effects of the C1431T and Pro12Ala PPARγ gene variants on plasma lipids and diabetes risk in an Asian population,” Journal of Lipid Research, vol. 45, no. 4, pp. 674–685, 2004. View at Publisher · View at Google Scholar · View at Scopus
  170. M. K. Moon, Y. M. Cho, H. S. Jung et al., “Genetic polymorphisms in peroxisome proliferator-activated receptor γ are associated with Type 2 diabetes mellitus and obesity in the Korean population,” Diabetic Medicine, vol. 22, no. 9, pp. 1161–1166, 2005. View at Publisher · View at Google Scholar · View at Scopus
  171. R. Meshkani, M. Taghikhani, B. Larijani et al., “Pro12Ala polymorphism of the peroxisome proliferator-activated receptor-γ2 (PPARγ-2) gene is associated with greater insulin sensitivity and decreased risk of type 2 diabetes in an Iranian population,” Clinical Chemistry and Laboratory Medicine, vol. 45, no. 4, pp. 477–482, 2007. View at Publisher · View at Google Scholar · View at Scopus
  172. A. Mansoori, M. Amini, F. Kolahdooz, and E. Seyedrezazadeh, “Obesity and Pro12Ala polymorphism of peroxisome proliferator-activated receptor-gamma gene in healthy adults: a systematic review and meta-analysis,” Annals of Nutrition and Metabolism, vol. 67, no. 2, pp. 104–118, 2015. View at Publisher · View at Google Scholar · View at Scopus
  173. J. Ma, Y. Li, F. Zhou, X. Xu, G. Guo, and Y. Qu, “Meta-analysis of association between the Pro12Ala polymorphism of the peroxisome proliferator-activated receptor- γ2 gene and diabetic retinopathy in Caucasians and Asians,” Molecular Vision, vol. 18, pp. 2352–2360, 2012. View at Google Scholar · View at Scopus
  174. A. Passaro, E. Dalla Nora, C. Marcello et al., “PPARγ Pro12Ala and ACE ID polymorphisms are associated with BMI and fat distribution, but not metabolic syndrome,” Cardiovascular Diabetology, vol. 10, article 112, 2011. View at Publisher · View at Google Scholar · View at Scopus
  175. J. Luan, P. O. Browne, A.-H. Harding et al., “Evidence for gene-nutrient interaction at the PPARγ locus,” Diabetes, vol. 50, no. 3, pp. 686–689, 2001. View at Publisher · View at Google Scholar · View at Scopus
  176. J. Pihlajamäki, U. Schwab, D. Kaminska et al., “Dietary polyunsaturated fatty acids and the Pro12Ala polymorphisms of PPARG regulate serum lipids through divergent pathways: a randomized crossover clinical trial,” Genes & Nutrition, vol. 10, no. 6, article 43, 2015. View at Publisher · View at Google Scholar · View at Scopus
  177. J. Robitaille, J.-P. Després, L. Pérusse, and M.-C. Vohl, “The PPAR-gamma P12A polymorphism modulates the relationship between dietary fat intake and components of the metabolic syndrome: results from the Québec Family Study,” Clinical Genetics, vol. 63, no. 2, pp. 109–116, 2003. View at Publisher · View at Google Scholar · View at Scopus
  178. N. Ouchi, S. Kihara, T. Funahashi, Y. Matsuzawa, and K. Walsh, “Obesity, adiponectin and vascular inflammatory disease,” Current Opinion in Lipidology, vol. 14, no. 6, pp. 561–566, 2003. View at Publisher · View at Google Scholar · View at Scopus
  179. L. B. Tankó, A. Siddiq, C. Lecoeur et al., “ACDC/adiponectin and PPAR-γ gene polymorphisms: implications for features of obesity,” Obesity Research, vol. 13, no. 12, pp. 2113–2121, 2005. View at Publisher · View at Google Scholar · View at Scopus
  180. W.-S. Yang, C. A. Hsiung, L.-T. Ho et al., “Genetic epistasis of adiponectin and PPARγ2 genotypes in modulation of insulin sensitivity: a family-based association study,” Diabetologia, vol. 46, no. 7, pp. 977–983, 2003. View at Publisher · View at Google Scholar · View at Scopus
  181. C.-Y. Cao, Y.-Y. Li, Y.-J. Zhou, Y.-Q. Nie, and Y.-J. Y. Wan, “The C-681G polymorphism of the PPAR-γ gene is associated with susceptibility to non-alcoholic fatty liver disease,” Tohoku Journal of Experimental Medicine, vol. 227, no. 4, pp. 253–262, 2012. View at Publisher · View at Google Scholar · View at Scopus
  182. Z. Yang, J. Wen, Q. Li et al., “PPARG gene Pro12Ala variant contributes to the development of non-alcoholic fatty liver in middle-aged and older Chinese population,” Molecular and Cellular Endocrinology, vol. 348, no. 1, pp. 255–259, 2012. View at Publisher · View at Google Scholar · View at Scopus
  183. S. Ereqat, A. Nasereddin, K. Azmi, Z. Abdeen, and R. Amin, “Impact of the pro12Ala polymorphism of the PPAR-gamma 2 gene on metabolic and clinical characteristics in the palestinian type 2 diabetic patients,” PPAR Research, vol. 2009, Article ID 874126, 5 pages, 2009. View at Publisher · View at Google Scholar · View at Scopus
  184. L. Gallicchio, B. Kalesan, H. Huang, P. Strickland, S. C. Hoffman, and K. J. Helzlsouer, “Genetic polymorphisms of peroxisome proliferator-activated receptors and the risk of cardiovascular morbidity and mortality in a community-based cohort in Washington County, Maryland,” PPAR Research, vol. 2008, Article ID 276581, 9 pages, 2008. View at Publisher · View at Google Scholar
  185. T.-H. Chao, Y.-H. Li, J.-H. Chen et al., “The 161TT genotype in the exon 6 of the peroxisome-proliferator-activated receptor γ gene is associated with premature acute myocardial infarction and increased lipid peroxidation in habitual heavy smokers,” Clinical Science, vol. 107, no. 5, pp. 461–466, 2004. View at Publisher · View at Google Scholar · View at Scopus
  186. A. Doney, B. Fischer, D. Frew et al., “Haplotype analysis of the PPARγ Pro12Ala and C1431T variants reveals opposing associations with body weight,” BMC Genetics, vol. 3, article 21, 2002. View at Publisher · View at Google Scholar
  187. A. Meirhaeghe, L. Fajas, N. Helbecque et al., “Impact of the peroxisome proliferator activated receptor γ2 Pro12Ala polymorphism on adiposity, lipids and non-insulin-dependent diabetes mellitus,” International Journal of Obesity and Related Metabolic Disorders, vol. 24, no. 2, pp. 195–199, 2000. View at Google Scholar
  188. C.-P. Dong, L. He, J.-N. Li, F. Ye, M. He, and Y. Wang, “Association of the Pro12Ala and C1431T polymorphism of the PPAR gamma2 gene and their haplotypes with obesity and type 2 diabetes,” Chinese Journal of Medical Genetics, vol. 25, no. 4, pp. 447–451, 2008. View at Google Scholar · View at Scopus
  189. J. Prakash, N. Srivastava, S. Awasthi et al., “Association of PPAR-γ gene polymorphisms with obesity and obesity-associated phenotypes in north indian population,” American Journal of Human Biology, vol. 24, no. 4, pp. 454–459, 2012. View at Publisher · View at Google Scholar · View at Scopus
  190. E. J. Rhee, K. W. Oh, W. Y. Lee et al., “Effects of two common polymorphisms of peroxisome proliferator-activated receptor-γ gene on metabolic syndrome,” Archives of Medical Research, vol. 37, no. 1, pp. 86–94, 2006. View at Publisher · View at Google Scholar · View at Scopus
  191. B. Heude, V. Pelloux, A. Forhan et al., “Association of the Pro12Ala and C1431T variants of PPARγ and their haplotypes with susceptibility to gestational diabetes,” Journal of Clinical Endocrinology and Metabolism, vol. 96, no. 10, pp. E1656–E1660, 2011. View at Publisher · View at Google Scholar · View at Scopus
  192. A. Haseeb, M. Iliyas, S. Chakrabarti et al., “Single-nucleotide polymorphisms in peroxisome proliferator-activated receptor γ and their association with plasma levels of resistin and the metabolic syndrome in a South Indian population,” Journal of Biosciences, vol. 34, no. 3, pp. 405–414, 2009. View at Publisher · View at Google Scholar · View at Scopus
  193. M. Oladi, M. Nohtani, A. Avan et al., “Impact of the C1431T polymorphism of the peroxisome proliferator activated receptor-gamma (PPAR-γ) gene on fasted serum lipid levels in patients with coronary artery disease,” Annals of Nutrition and Metabolism, vol. 66, no. 2-3, pp. 149–154, 2015. View at Publisher · View at Google Scholar · View at Scopus
  194. X. Zhou, J. Chen, and W. Xu, “Association between C1431T polymorphism in peroxisome proliferator-activated receptor-γ gene and coronary artery disease in Chinese Han population,” Molecular Biology Reports, vol. 39, no. 2, pp. 1863–1868, 2012. View at Publisher · View at Google Scholar · View at Scopus
  195. R. Valve, K. Sivenius, R. Miettinen et al., “Two polymorphisms in the peroxisome proliferator-activated receptor-γ gene are associated with severe overweight among obese women,” Journal of Clinical Endocrinology and Metabolism, vol. 84, no. 10, pp. 3708–3712, 1999. View at Google Scholar · View at Scopus
  196. 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
  197. Y.-S. Cha, Y. Park, M. Lee et al., “Doenjang, a korean fermented soy food, exerts antiobesity and antioxidative activities in overweight subjects with the PPAR-γ2 C1431T polymorphism: 12-week, double-blind randomized clinical trial,” Journal of Medicinal Food, vol. 17, no. 1, pp. 119–127, 2014. View at Publisher · View at Google Scholar · View at Scopus
  198. M. M. Swarbrick, C. M. L. Chapman, B. M. McQuillan, J. Hung, P. L. Thompson, and J. P. Beilby, “A Pro12Ala polymorphism in the human peroxisome proliferator-activated receptor-γ2 is associated with combined hyperlipidaemia in obesity,” European Journal of Endocrinology, vol. 144, no. 3, pp. 277–282, 2001. View at Publisher · View at Google Scholar · View at Scopus
  199. O. W. Hamer, D. Forstner, I. Ottinger et al., “The pro115Gln polymorphism within the PPAR γ2 gene has no epidemiological impact on morbid obesity,” Experimental and Clinical Endocrinology and Diabetes, vol. 110, no. 5, pp. 230–234, 2002. View at Publisher · View at Google Scholar · View at Scopus