Celastrol protects against obesity and metabolic dysfunction through activation of a HSF1-PGC1α transcriptional axis

Cell Metabolism

Volumn 22, Issue 4, 2015, Pages 695-708

  Ma, Xinran ^a   Xu, Lingyan ^a   Alberobello, Anna Teresa ^a   Gavrilova, Oksana ^a   Bagattin, Alessia ^a   Skarulis, Monica ^a   Liu, Jie ^b   Finkel, Toren ^b   Mueller, Elisabetta ^a  

^a NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES   (United States)

^b NATIONAL HEART LUNG AND BLOOD INSTITUTE   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ALANINE AMINOTRANSFERASE; CELASTROL; HEAT SHOCK TRANSCRIPTION FACTOR 1; PEROXISOME PROLIFERATOR ACTIVATED RECEPTOR GAMMA COACTIVATOR 1ALPHA; DNA BINDING PROTEIN; HSF1 PROTEIN, MOUSE; PPARGC1A PROTEIN, MOUSE; TRANSCRIPTION FACTOR; TRIACYLGLYCEROL; TRIPTERINE; TRITERPENE;

ADIPOSE TISSUE; ALANINE AMINOTRANSFERASE BLOOD LEVEL; ANIMAL EXPERIMENT; ANIMAL MODEL; ARTICLE; BROWN ADIPOSE TISSUE; CONTROLLED STUDY; ENERGY EXPENDITURE; ENERGY METABOLISM; FATTY LIVER; GENETIC MANIPULATION; HUMAN; HUMAN TISSUE; IN VITRO STUDY; IN VIVO STUDY; INSULIN RESISTANCE; KNOCKOUT MOUSE; LIPID DIET; METABOLIC DISORDER; MITOCHONDRION; MOUSE; MUSCLE TISSUE; NONHUMAN; OBESITY; PRIORITY JOURNAL; THERMOGENESIS; WHITE ADIPOSE TISSUE; ANIMAL; ANTAGONISTS AND INHIBITORS; BLOOD; C57BL MOUSE; CELL CULTURE; CYTOLOGY; DEFICIENCY; DRUG EFFECTS; FEMALE; GENETICS; LIVER; METABOLIC SYNDROME X; METABOLISM; PATHOLOGY; PROMOTER REGION;

ADIPOSE TISSUE, BROWN; ADIPOSE TISSUE, WHITE; ANIMALS; CELLS, CULTURED; DIET, HIGH-FAT; DNA-BINDING PROTEINS; ENERGY METABOLISM; FATTY LIVER; FEMALE; HUMANS; LIVER; METABOLIC SYNDROME X; MICE; MICE, INBRED C57BL; MICE, KNOCKOUT; OBESITY; PROMOTER REGIONS, GENETIC; THERMOGENESIS; TRANSCRIPTION FACTORS; TRIGLYCERIDES; TRITERPENES;

EID: 84943455845     PISSN: 15504131     EISSN: 19327420     Source Type: Journal    
DOI: 10.1016/j.cmet.2015.08.005     Document Type: Article

References (57)

1. J. Anckar, and L. Sistonen Regulation of HSF1 function in the heat stress response: implications in aging and disease Annu. Rev. Biochem. 80 2011 1089 1115
2. A. Bagattin, L. Hugendubler, and E. Mueller Transcriptional coactivator PGC-1α promotes peroxisomal remodeling and biogenesis Proc. Natl. Acad. Sci. USA 107 2010 20376 20381
3. O. Boss, and S.R. Farmer Recruitment of brown adipose tissue as a therapy for obesity-associated diseases Front. Endocrinol. (Lausanne) 3 2012 14
4. J.C. Bournat, and C.W. Brown Mitochondrial dysfunction in obesity Curr. Opin. Endocrinol. Diabetes Obes. 17 2010 446 452
5. C. Cantó, and J. Auwerx PGC-1α, SIRT1 and AMPK, an energy sensing network that controls energy expenditure Curr. Opin. Lipidol. 20 2009 98 105
6. A.E. Charos, B.D. Reed, D. Raha, A.M. Szekely, S.M. Weissman, and M. Snyder A highly integrated and complex PPARGC1A transcription factor binding network in HepG2 cells Genome Res. 22 2012 1668 1679
7. P. Cohen, J.D. Levy, Y. Zhang, A. Frontini, D.P. Kolodin, K.J. Svensson, J.C. Lo, X. Zeng, L. Ye, M.J. Khandekar, and et al. Ablation of PRDM16 and beige adipose causes metabolic dysfunction and a subcutaneous to visceral fat switch Cell 156 2014 304 316
8. K.E. Cullen, and K.D. Sarge Characterization of hypothermia-induced cellular stress response in mouse tissues J. Biol. Chem. 272 1997 1742 1746
9. J.T. Cunningham, J.T. Rodgers, D.H. Arlow, F. Vazquez, V.K. Mootha, and P. Puigserver mTOR controls mitochondrial oxidative function through a YY1-PGC-1α transcriptional complex Nature 450 2007 736 740
10. A.M. Cypess, and C.R. Kahn Brown fat as a therapy for obesity and diabetes Curr. Opin. Endocrinol. Diabetes Obes. 17 2010 143 149
11. A.M. Cypess, S. Lehman, G. Williams, I. Tal, D. Rodman, A.B. Goldfine, F.C. Kuo, E.L. Palmer, Y.H. Tseng, A. Doria, and et al. Identification and importance of brown adipose tissue in adult humans N. Engl. J. Med. 360 2009 1509 1517
12. A.M. Cypess, Y.C. Chen, C. Sze, K. Wang, J. English, O. Chan, A.R. Holman, I. Tal, M.R. Palmer, G.M. Kolodny, and C.R. Kahn Cold but not sympathomimetics activates human brown adipose tissue in vivo Proc. Natl. Acad. Sci. USA 109 2012 10001 10005
13. D.L. Eastmond, and H.C. Nelson Genome-wide analysis reveals new roles for the activation domains of the Saccharomyces cerevisiae heat shock transcription factor (Hsf1) during the transient heat shock response J. Biol. Chem. 281 2006 32909 32921
14. B. Egan, B.P. Carson, P.M. Garcia-Roves, A.V. Chibalin, F.M. Sarsfield, N. Barron, N. McCaffrey, N.M. Moyna, J.R. Zierath, and D.J. O'Gorman Exercise intensity-dependent regulation of PGC1α mRNA abundance is associated with differential activation of upstream signalling kinases in human skeletal muscle J. Physiol. 588 2010 1779 1790
15. S.R. Farmer Molecular determinants of brown adipocyte formation and function Genes Dev. 22 2008 1269 1275
16. N. Fujikake, Y. Nagai, H.A. Popiel, Y. Okamoto, M. Yamaguchi, and T. Toda Heat shock transcription factor 1-activating compounds suppress polyglutamine-induced neurodegeneration through induction of multiple molecular chaperones J. Biol. Chem. 283 2008 26188 26197
17. S. Gesta, Y.H. Tseng, and C.R. Kahn Developmental origin of fat: tracking obesity to its source Cell 131 2007 242 256
18. L. Guo, S. Chen, K. Liu, Y. Liu, L. Ni, K. Zhang, and L. Zhang Isolation of heat shock factor HsfA1a-binding sites in vivo revealed variations of heat shock elements in Arabidopsis thaliana Plant Cell Physiol. 49 2008 1306 1315
19. C. Handschin, and B.M. Spiegelman Peroxisome proliferator-activated receptor γ coactivator 1 coactivators, energy homeostasis, and metabolism Endocr. Rev. 27 2006 728 735
20. C. Handschin, J. Rhee, J. Lin, P.T. Tarr, and B.M. Spiegelman An autoregulatory loop controls peroxisome proliferator-activated receptor γ coactivator 1α expression in muscle Proc. Natl. Acad. Sci. USA 100 2003 7111 7116
21. C. Handschin, Y.M. Kobayashi, S. Chin, P. Seale, K.P. Campbell, and B.M. Spiegelman PGC-1α regulates the neuromuscular junction program and ameliorates Duchenne muscular dystrophy Genes Dev. 21 2007 770 783
22. M. Harms, and P. Seale Brown and beige fat: development, function and therapeutic potential Nat. Med. 19 2013 1252 1263
23. M. Kiaei, K. Kipiani, S. Petri, J. Chen, N.Y. Calingasan, and M.F. Beal Celastrol blocks neuronal cell death and extends life in transgenic mouse model of amyotrophic lateral sclerosis Neurodegener. Dis. 2 2005 246 254
24. S. Kleiner, R.J. Mepani, D. Laznik, L. Ye, M.J. Jurczak, F.R. Jornayvaz, J.L. Estall, D. Chatterjee Bhowmick, G.I. Shulman, and B.M. Spiegelman Development of insulin resistance in mice lacking PGC-1α in adipose tissues Proc. Natl. Acad. Sci. USA 109 2012 9635 9640
25. D. Kraus, Q. Yang, D. Kong, A.S. Banks, L. Zhang, J.T. Rodgers, E. Pirinen, T.C. Pulinilkunnil, F. Gong, Y.C. Wang, and et al. Nicotinamide N-methyltransferase knockdown protects against diet-induced obesity Nature 508 2014 258 262
26. M. Lagouge, C. Argmann, Z. Gerhart-Hines, H. Meziane, C. Lerin, F. Daussin, N. Messadeq, J. Milne, P. Lambert, P. Elliott, and et al. Resveratrol improves mitochondrial function and protects against metabolic disease by activating SIRT1 and PGC-1α Cell 127 2006 1109 1122
27. T.C. Leone, J.J. Lehman, B.N. Finck, P.J. Schaeffer, A.R. Wende, S. Boudina, M. Courtois, D.F. Wozniak, N. Sambandam, C. Bernal-Mizrachi, and et al. PGC-1α deficiency causes multi-system energy metabolic derangements: muscle dysfunction, abnormal weight control and hepatic steatosis PLoS Biol. 3 2005 e101
28. C. Lerin, J.T. Rodgers, D.E. Kalume, S.H. Kim, A. Pandey, and P. Puigserver GCN5 acetyltransferase complex controls glucose metabolism through transcriptional repression of PGC-1α Cell Metab. 3 2006 429 438
29. Y. Li, T. Fromme, S. Schweizer, T. Schöttl, and M. Klingenspor Taking control over intracellular fatty acid levels is essential for the analysis of thermogenic function in cultured primary brown and brite/beige adipocytes EMBO Rep. 15 2014 1069 1076
30. J. Lin, H. Wu, P.T. Tarr, C.Y. Zhang, Z. Wu, O. Boss, L.F. Michael, P. Puigserver, E. Isotani, E.N. Olson, and et al. Transcriptional co-activator PGC-1 α drives the formation of slow-twitch muscle fibres Nature 418 2002 797 801
31. J. Lin, P.H. Wu, P.T. Tarr, K.S. Lindenberg, J. St-Pierre, C.Y. Zhang, V.K. Mootha, S. Jäger, C.R. Vianna, R.M. Reznick, and et al. Defects in adaptive energy metabolism with CNS-linked hyperactivity in PGC-1α null mice Cell 119 2004 121 135
32. J. Liu, J. Lee, M.A. Salazar Hernandez, R. Mazitschek, and U. Ozcan Treatment of obesity with celastrol Cell 161 2015 999 1011
33. J.Z. Long, K.J. Svensson, L. Tsai, X. Zeng, H.C. Roh, X. Kong, R.R. Rao, J. Lou, I. Lokurkar, W. Baur, and et al. A smooth muscle-like origin for beige adipocytes Cell Metab. 19 2014 810 820
34. D. Ma, S. Li, E.K. Lucas, R.M. Cowell, and J.D. Lin Neuronal inactivation of PGC-1α protects mice from diet-induced obesity and leads to degenerative lesions J. Biol. Chem. 285 2010 39087 39095
35. X. Ma, L. Xu, O. Gavrilova, and E. Mueller Role of forkhead box protein A3 in age-associated metabolic decline Proc. Natl. Acad. Sci. USA 111 2014 14289 14294
36. M.L. Mendillo, S. Santagata, M. Koeva, G.W. Bell, R. Hu, R.M. Tamimi, E. Fraenkel, T.A. Ince, L. Whitesell, and S. Lindquist HSF1 drives a transcriptional program distinct from heat shock to support highly malignant human cancers Cell 150 2012 549 562
37. J.F. Morley, and R.I. Morimoto Regulation of longevity in Caenorhabditis elegans by heat shock factor and molecular chaperones Mol. Biol. Cell 15 2004 657 664
38. E. Mueller Understanding the variegation of fat: novel regulators of adipocyte differentiation and fat tissue biology Biochim. Biophys. Acta 1842 2014 352 357
39. J. Nedergaard, and B. Cannon The browning of white adipose tissue: some burning issues Cell Metab. 20 2014 396 407
40. V. Ouellet, S.M. Labbé, D.P. Blondin, S. Phoenix, B. Guérin, F. Haman, E.E. Turcotte, D. Richard, and A.C. Carpentier Brown adipose tissue oxidative metabolism contributes to energy expenditure during acute cold exposure in humans J. Clin. Invest. 122 2012 545 552
41. D. Paris, N.J. Ganey, V. Laporte, N.S. Patel, D. Beaulieu-Abdelahad, C. Bachmeier, A. March, G. Ait-Ghezala, and M.J. Mullan Reduction of beta-amyloid pathology by celastrol in a transgenic mouse model of Alzheimer's disease J. Neuroinflammation 7 2010 17
42. M.E. Patti, and S. Corvera The role of mitochondria in the pathogenesis of type 2 diabetes Endocr. Rev. 31 2010 364 395
43. S.W. Qian, Y. Tang, X. Li, Y. Liu, Y.Y. Zhang, H.Y. Huang, R.D. Xue, H.Y. Yu, L. Guo, H.D. Gao, and et al. BMP4-mediated brown fat-like changes in white adipose tissue alter glucose and energy homeostasis Proc. Natl. Acad. Sci. USA 110 2013 E798 E807
44. H. Reinke, C. Saini, F. Fleury-Olela, C. Dibner, I.J. Benjamin, and U. Schibler Differential display of DNA-binding proteins reveals heat-shock factor 1 as a circadian transcription factor Genes Dev. 22 2008 331 345
45. J.L. Ruas, J.P. White, R.R. Rao, S. Kleiner, K.T. Brannan, B.C. Harrison, N.P. Greene, J. Wu, J.L. Estall, B.A. Irving, and et al. A PGC-1α isoform induced by resistance training regulates skeletal muscle hypertrophy Cell 151 2012 1319 1331
46. A. Salminen, M. Lehtonen, T. Paimela, and K. Kaarniranta Celastrol: Molecular targets of Thunder God Vine Biochem. Biophys. Res. Commun. 394 2010 439 442
47. L.Z. Sharp, K. Shinoda, H. Ohno, D.W. Scheel, E. Tomoda, L. Ruiz, H. Hu, L. Wang, Z. Pavlova, V. Gilsanz, and S. Kajimura Human BAT possesses molecular signatures that resemble beige/brite cells PLoS ONE 7 2012 e49452
48. M.C. Skarulis, F.S. Celi, E. Mueller, M. Zemskova, R. Malek, L. Hugendubler, C. Cochran, J. Solomon, C. Chen, and P. Gorden Thyroid hormone induced brown adipose tissue and amelioration of diabetes in a patient with extreme insulin resistance J. Clin. Endocrinol. Metab. 95 2010 256 262
49. J. St-Pierre, S. Drori, M. Uldry, J.M. Silvaggi, J. Rhee, S. Jäger, C. Handschin, K. Zheng, J. Lin, W. Yang, and et al. Suppression of reactive oxygen species and neurodegeneration by the PGC-1 transcriptional coactivators Cell 127 2006 397 408
50. M.H. Tschöp, J.R. Speakman, J.R. Arch, J. Auwerx, J.C. Brüning, L. Chan, R.H. Eckel, R.V. Farese Jr., J.E. Galgani, C. Hambly, and et al. A guide to analysis of mouse energy metabolism Nat. Methods 9 2011 57 63
51. S.D. Westerheide, J.D. Bosman, B.N. Mbadugha, T.L. Kawahara, G. Matsumoto, S. Kim, W. Gu, J.P. Devlin, R.B. Silverman, and R.I. Morimoto Celastrols as inducers of the heat shock response and cytoprotection J. Biol. Chem. 279 2004 56053 56060
52. A.J. Whittle, S. Carobbio, L. Martins, M. Slawik, E. Hondares, M.J. Vázquez, D. Morgan, R.I. Csikasz, R. Gallego, S. Rodriguez-Cuenca, and et al. BMP8B increases brown adipose tissue thermogenesis through both central and peripheral actions Cell 149 2012 871 885
53. Z. Wu, P. Puigserver, U. Andersson, C. Zhang, G. Adelmant, V. Mootha, A. Troy, S. Cinti, B. Lowell, R.C. Scarpulla, and B.M. Spiegelman Mechanisms controlling mitochondrial biogenesis and respiration through the thermogenic coactivator PGC-1 Cell 98 1999 115 124
54. J. Wu, P. Boström, L.M. Sparks, L. Ye, J.H. Choi, A.H. Giang, M. Khandekar, K.A. Virtanen, P. Nuutila, G. Schaart, and et al. Beige adipocytes are a distinct type of thermogenic fat cell in mouse and human Cell 150 2012 366 376
55. Y.M. Xu, D.Y. Huang, J.F. Chiu, and A.T. Lau Post-translational modification of human heat shock factors and their functions: a recent update by proteomic approach J. Proteome Res. 11 2012 2625 2634
56. H. Yang, D. Chen, Q.C. Cui, X. Yuan, and Q.P. Dou Celastrol, a triterpene extracted from the Chinese "Thunder of God Vine," is a potent proteasome inhibitor and suppresses human prostate cancer growth in nude mice Cancer Res. 66 2006 4758 4765
57. L. Ye, J. Wu, P. Cohen, L. Kazak, M.J. Khandekar, M.P. Jedrychowski, X. Zeng, S.P. Gygi, and B.M. Spiegelman Fat cells directly sense temperature to activate thermogenesis Proc. Natl. Acad. Sci. USA 110 2013 12480 12485