Citation: Li Xiang, Juan Nie, Li Wang, Yu Wang, Jingchun Shi, Juntong Wei, Chi-Wai Lau, Zongwei Cai, Yu Huang. Integrated metabolomics analysis of the effect of PPARδ agonist GW501516 on catabolism of BCAAs and carboxylic acids in diabetic mice[J]. Chinese Chemical Letters, ;2021, 32(7): 2197-2202. doi: 10.1016/j.cclet.2020.12.042 shu

Integrated metabolomics analysis of the effect of PPARδ agonist GW501516 on catabolism of BCAAs and carboxylic acids in diabetic mice

Li Xiang ^{a, 1} ,
Juan Nie ^{b, 1} ,
Li Wang ^a ,
Yu Wang ^a ,
Jingchun Shi ^b ,
Juntong Wei ^b ,
Chi-Wai Lau ^a ,
Zongwei Cai ^{b, *,} ,
Yu Huang ^{a, *,}

a.
Heart and Vascular Institute, School of Biomedical Sciences and Shenzhen Research Institute, Chinese University of Hong Kong, Hong Kong, China
b.
State Key Laboratory of Environmental and Biological Analysis and Department of Chemistry, Hong Kong Baptist University, Hong Kong, China

zwcai@hkbu.edu.hk

yu-huang@cuhk.edu.hk

Received Date: 9 October 2020
Revised Date: 15 November 2020
Accepted Date: 23 December 2020
Available Online: 25 December 2020

Figures(4)

The peroxisome proliferator-activated receptor (PPARδ) agonists are reported to improve insulin sensitivity, reduce glucose levels, and alleviate dysfunctional lipid metabolism in animal models of type 2 diabetes mellitus. However, the underlying mechanisms remain incompletely understood. Metabolism plays an essential role in the biological system. Monitoring of metabolic changes in response to disease conditions or drug treatment is critical for better understanding of the pathophysiological mechanisms. In this study, metabolic profiling analysis by gas chromatography-mass spectrometry integrated with targeted analysis by liquid chromatography-mass spectrometry was carried out in plasma samples of db/db diabetic mice after six-week treatment of PPARδ agonist GW501516. GW501516 treatment significantly altered levels of metabolites, such as branched-chain amino acids (BCAAs), BCAA metabolites (3-hydroxyisobutyric acid and 3-hydroxyisovaleric acid), long-chain fatty acids, uric acid and ketone bodies (3-hydroxybutyric acid and 2-hydroxybutyric acid) which are all associated with the impaired systemic insulin sensitivity. The present results indicate the beneficial effect of PPARδ agonist in alleviating insulin resistance of diabetic mice by favorably modulating metabolic profile, thus providing valuable information in understanding the therapeutic potential of PPARδ agonists in correcting metabolic dysfunction in diabetes.
- PPARδ,
- BCAAs,
- BCAA metabolites,
- Metabolomics,
- Diabetic mice
1. [1]
  B.C. Martin, J.H. Warram, A.S. Krolewski, et al., Lancet 340(1992) 925-929. doi: 10.1016/0140-6736(92)92814-V
2. [2]
  A. Tenenbaum, E.Z. Fisman, M. Motro, Cardiovasc. Diabetol. 2(2003) 4. doi: 10.1186/1475-2840-2-4
3. [3]
  J. Vamecq, N. Latruffe, Lancet 354(1999) 141-148. doi: 10.1016/S0140-6736(98)10364-1
4. [4]
  J. Berger, D.E. Moller, Annu. Rev. Med. 53(2002) 409-435. doi: 10.1146/annurev.med.53.082901.104018
5. [5]
  G. Chinetti, J.C. Fruchart, B. Staels, Inflamm. Res. 49(2000) 497-505. doi: 10.1007/s000110050622
6. [6]
  A. Jawerbaum, E. Capobianco, Placenta 32(2011) S212-S217. doi: 10.1016/j.placenta.2010.12.002
7. [7]
  D. Kim, M. Bility, A. Billin, et al., Cell Death Differ. 13(2006) 53-60. doi: 10.1038/sj.cdd.4401713
8. [8]
  C. Jiang, A.T. Ting, B. Seed, Nature 391(1998) 82-86. doi: 10.1038/34184
9. [9]
  B.P. Kota, T.H.W. Huang, B.D. Roufogalis, Pharmacol. Res. 51(2005) 85-94. doi: 10.1016/j.phrs.2004.07.012
10. [10]
  U. Dressel, T.L. Allen, J.B. Pippal, et al., Mol. Endocrinol. 17(2003) 2477-2493. doi: 10.1210/me.2003-0151
11. [11]
  D.K. Krämer, L. Al-Khalili, B. Guigas, et al., J. Biol. Chem. 282(2007) 19313-19320. doi: 10.1074/jbc.M702329200
12. [12]
  W. Chen, L.L. Wang, H.Y. Liu, etal., BasicClin. Pharm. Toxicol. 103(2008)240-246. doi: 10.1111/j.1742-7843.2008.00268.x
13. [13]
  O. Beckonert, H.C. Keun, T.M. Ebbels, et al., Nat. Protoc. 2(2007) 2692. doi: 10.1038/nprot.2007.376
14. [14]
  Y. Qi, Z.F. Pi, S. Liu, et al., Chin. Chem. Lett. 26(2015) 387-392. doi: 10.1016/j.cclet.2014.11.017
15. [15]
  A. -L. Barabasi, Z.N. Oltvai, Nat. Rev. Gen. 5(2004) 101-113. doi: 10.1038/nrg1272
16. [16]
  L. Xiang, H. Zhang, J. Wei, et al., Anal. Chim. Acta 1037(2018) 130-139. doi: 10.1016/j.aca.2017.11.082
17. [17]
  R.J. Li, X.J. Kou, H. Geng, et al., Chin. Chem. Lett. 25(2014) 663-666. doi: 10.1016/j.cclet.2014.03.032
18. [18]
  Z.Z. Cheng, Z.H. Jia, Y. Chen, et al., Chin. Chem. Lett. 17(2006) 1057-1060.
19. [19]
  T. Tanaka, J. Yamamoto, S. Iwasaki, et al., Proc. Nat. Acad. Sci. U. S. A. 100(2003) 15924-15929. doi: 10.1073/pnas.0306981100
20. [20]
  Y.X. Wang, C.L. Zhang, T.Y. Ruth, et al., PLoS Biol. 2(2004) 1532-1539. doi: 10.4049/jimmunol.173.1.61
21. [21]
  J. Wei, L. Xiang, X. Li, et al., Anal. Chim. Acta 1100(2020) 66-74. doi: 10.1016/j.aca.2019.11.009
22. [22]
  J. Han, R. Higgins, M.D. Lim, et al., Anal. Chim. Acta 1037(2018) 177-187. doi: 10.1016/j.aca.2018.01.045
23. [23]
  J. Chong, D.S. Wishart, J. Xia, Curr. Protoc. Bioinform. 68(2019) e86.
24. [24]
  K.G.M.M. Alberti, P.Z. Zimmet, Diab. Med. 15(1998) 539-553. doi: 10.1002/(SICI)1096-9136(199807)15:7<539::AID-DIA668>3.0.CO;2-S
25. [25]
  S.E. Kahn, R.L. Hull, K.M. Utzschneider, Nature 444(2006) 840-846. doi: 10.1038/nature05482
26. [26]
  C.J. Lynch, S.H. Adams, Nat. Rev. Endocrinol. 10(2014) 723-736. doi: 10.1038/nrendo.2014.171
27. [27]
  H. Li, M. Xu, J. Lee, et al., Am. J. Physiol. -Endocrinol. Metabol. 303(2012) E1234-E1244. doi: 10.1152/ajpendo.00198.2012
28. [28]
  K. Guo, Y.H. Yu, J. Hou, et al., Nutr. Metabol. 7(2010) 57. doi: 10.1186/1743-7075-7-57
29. [29]
  Y. Zhang, K. Guo, R.E. LeBlanc, et al., Diabetes 56(2007) 1647-1654. doi: 10.2337/db07-0123
30. [30]
  S. Shah, D. Crosslin, C. Haynes, et al., Diabetologia 55(2012) 321-330. doi: 10.1007/s00125-011-2356-5
31. [31]
  H. Nakamura, H. Jinzu, K. Nagao, et al., Nutrit. Diabetes 4(2014) e133-e133. doi: 10.1038/nutd.2014.32
32. [32]
  C.B. Newgard, J. An, J.R. Bain, et al., Cell Metab. 9(2009) 311-326. doi: 10.1016/j.cmet.2009.02.002
33. [33]
  M. Doisaki, Y. Katano, I. Nakano, et al., Biochem. Biophys. Res. Commun. 393(2010) 303-307. doi: 10.1016/j.bbrc.2010.02.004
34. [34]
  S.C. Connor, M.K. Hansen, A. Corner, et al., Mol. Biosyst. 6(2010) 909-921. doi: 10.1039/b914182k
35. [35]
  C.B. Newgard, Cell Metab. 15(2012) 606-614. doi: 10.1016/j.cmet.2012.01.024
36. [36]
  F. Badoud, K.P. Lam, A. DiBattista, et al., J. Proteom. Res. 13(2014) 3455-3466. doi: 10.1021/pr500416v
37. [37]
  E. Tai, M. Tan, R. Stevens, et al., Diabetologia 53(2010) 757-767. doi: 10.1007/s00125-009-1637-8
38. [38]
  C. Jang, S.F. Oh, S. Wada, et al., Nat. Med. 22(2016) 421-426. doi: 10.1038/nm.4057
39. [39]
  M. Kılıç, N. Kaymaz, R.K. Özgül, J. Clin. Res. Pediatr. Endocrinol. 6(2014) 59-61. doi: 10.4274/Jcrpe.1181
40. [40]
  E.S. Gordon, Am. J. Clin. Nutr. 8(1960) 740-747. doi: 10.1093/ajcn/8.5.740
41. [41]
  L.D. Han, J.F. Xia, Q.L. Liang, et al., Anal. Chim. Acta 689(2011) 85-91. doi: 10.1016/j.aca.2011.01.034
42. [42]
  G.I. Shulman, J. Clin. Invest. 106(2000) 171-176. doi: 10.1172/JCI10583
43. [43]
  M.G. Bixel, J. Engelmann, W. Willker, et al., Neurochem. Res. 29(2004) 2057-2067. doi: 10.1007/s11064-004-6879-8
44. [44]
  S. Landaas, Clin. Chim. Acta 58(1975) 23-32. doi: 10.1016/0009-8981(75)90481-7
45. [45]
  W.E. Gall, K. Beebe, K.A. Lawton, et al., PLoS One 5(2010) e10883. doi: 10.1371/journal.pone.0010883
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