Treatment of Obesity with Celastrol
Open accessAbstract
Despite all modern advances in medicine, an effective drug treatment of obesity has not been found yet. Discovery of leptin two decades ago created hopes for treatment of obesity. However, development of leptin resistance has been a big obstacle, mitigating a leptin-centric treatment of obesity. Here, by using in silico drug-screening methods, we discovered that Celastrol, a pentacyclic triterpene extracted from the roots of Tripterygium Wilfordi (thunder god vine) plant, is a powerful anti-obesity agent. Celastrol suppresses food intake, blocks reduction of energy expenditure, and leads to up to 45% weight loss in hyperleptinemic diet-induced obese (DIO) mice by increasing leptin sensitivity, but it is ineffective in leptin-deficient (ob/ob) and leptin receptor-deficient (db/db) mouse models. These results indicate that Celastrol is a leptin sensitizer and a promising agent for the pharmacological treatment of obesity.
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The decreasing body weight and reduced food intake in celastrol-treated mice could be associated with celastrol's potential to enhance leptin sensitivity, thereby suppressing appetite.
“This could be associated with celastrol’s potential to enhance leptin sensitivity, thereby suppressing appetite [36].”
From Celastrol attenuates the invasion and migration and augments the anticancer effects of olaparib in prostate cancer (2024) · cites this paper as [36]
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Cites
Positional cloning of the mouse obese gene and its human homologue
Zhang, Y., Proenca, R., Maffei, M., Barone, M., Leopold, L., & Friedman, J. M. (1994) · Nature · doi:10.1038/372425a0 · Cited by 13,419 · see citing works
Finucane, M. M., Stevens, G. A., Cowan, M. J., Danaei, G., Lin, J. K., Paciorek, C. J., Singh, G. M., Gutierrez, H. R., Lu, Y., Bahalim, A. N., et al. (2011) · The Lancet · doi:10.1016/s0140-6736(10)62037-5 · Cited by 4,050 · see citing works
Global burden of obesity in 2005 and projections to 2030
Kelly, T., Yang, W., Chen, C.-S., Reynolds, K., & He, J. (2008) · International Journal of Obesity · doi:10.1038/ijo.2008.102 · Cited by 3,319 · see citing works
Leptin at 14 y of age: an ongoing story
Friedman, J. M. (2009) · The American Journal of Clinical Nutrition · doi:10.3945/ajcn.2008.26788b · Cited by 272 · see citing works
Flagged first, then by citations
Research works printed but not linked: 27
- Coleman DL 1978 Obese and diabetes: two mutant genes causing diabetes-obesity syndromes in mice Diabetologia 14 141 148 350680
- Considine RV Sinha MK Heiman ML Kriauciunas A Stephens TW Nyce MR Ohannesian JP Marco CC McKee LJ Bauer TL 1996 Serum immunoreactive-leptin concentrations in normal-weight and obese humans The New England journal of medicine 334 292 295 8532024
- Corson TW Crews CM 2007 Molecular understanding and modern application of traditional medicines: triumphs and trials Cell 130 769 774 17803898 PMC2507744
- de Almeida SF Picarote G Fleming JV Carmo-Fonseca M Azevedo JE de Sousa M 2007 Chemical chaperones reduce endoplasmic reticulum stress and prevent mutant HFE aggregate formation The Journal of biological chemistry 282 27905 27912 17626021
- Dietrich MO Horvath TL 2013 Hypothalamic control of energy balance: insights into the role of synaptic plasticity Trends in neurosciences 36 65 73 23318157
- Frederich RC Hamann A Anderson S Lollmann B Lowell BB Flier JS 1995 Leptin levels reflect body lipid content in mice: evidence for diet-induced resistance to leptin action Nature medicine 1 1311 1314 7489415
- Friedman JM 2004 Modern science versus the stigma of obesity Nature medicine 10 563 569 15170194
- Halaas JL Boozer C Blair-West J Fidahusein N Denton DA Friedman JM 1997 Physiological response to long-term peripheral and central leptin infusion in lean and obese mice Proceedings of the National Academy of Sciences of the United States of America 94 8878 8883 9238071 PMC23177
- Halaas JL Gajiwala KS Maffei M Cohen SL Chait BT Rabinowitz D Lallone RL Burley SK Friedman JM 1995 Weight-reducing effects of the plasma protein encoded by the obese gene Science 269 543 546 7624777
- Hieronymus H Lamb J Ross KN Peng XP Clement C Rodina A Nieto M Du J Stegmaier K Raj SM 2006 Gene expression signature-based chemical genomic prediction identifies a novel class of HSP90 pathway modulators Cancer cell 10 321 330 17010675
- Lamb J Crawford ED Peck D Modell JW Blat IC Wrobel MJ Lerner J Brunet JP Subramanian A Ross KN 2006 The Connectivity Map: using gene-expression signatures to connect small molecules, genes, and disease Science 313 1929 1935 17008526
- Lee J Ozcan U 2014 Unfolded protein response signaling and metabolic diseases The Journal of biological chemistry 289 1203 1211 24324257 PMC3894306
- Lee JH Koo TH Yoon H Jung HS Jin HZ Lee K Hong YS Lee JJ 2006 Inhibition of NF-kappa B activation through targeting I kappa B kinase by celastrol, a quinone methide triterpenoid Biochemical pharmacology 72 1311 1321 16984800
- Liou AP Paziuk M Luevano JM Jr Machineni S Turnbaugh PJ Kaplan LM 2013 Conserved shifts in the gut microbiota due to gastric bypass reduce host weight and adiposity Science translational medicine 5 178ra141 PMC3652229 23536013
- Mokadem M Zechner JF Margolskee RF Drucker DJ Aguirre V 2014 Effects of Roux-en-Y gastric bypass on energy and glucose homeostasis are preserved in two mouse models of functional glucagon-like peptide-1 deficiency Molecular metabolism 3 191 201 24634822 PMC3953682
- Myers MG Jr Leibel RL Seeley RJ Schwartz MW 2010 Obesity and leptin resistance: distinguishing cause from effect Trends in endocrinology and metabolism: TEM 21 643 651 20846876 PMC2967652
- Neckers L 2007 Heat shock protein 90: the cancer chaperone Journal of biosciences 32 517 530 17536171
- Olshansky SJ Passaro DJ Hershow RC Layden J Carnes BA Brody J Hayflick L Butler RN Allison DB Ludwig DS 2005 A potential decline in life expectancy in the United States in the 21st century The New England journal of medicine 352 1138 1145 15784668
- Ozcan L Ergin AS Lu A Chung J Sarkar S Nie D Myers MG Jr Ozcan U 2009 Endoplasmic reticulum stress plays a central role in development of leptin resistance Cell metabolism 9 35 51 19117545
- Ozcan U Cao Q Yilmaz E Lee AH Iwakoshi NN Ozdelen E Tuncman G Gorgun C Glimcher LH Hotamisligil GS 2004 Endoplasmic reticulum stress links obesity, insulin action, and type 2 diabetes Science 306 457 461 15486293
- Ozcan U Ozcan L Yilmaz E Duvel K Sahin M Manning BD Hotamisligil GS 2008 Loss of the tuberous sclerosis complex tumor suppressors triggers the unfolded protein response to regulate insulin signaling and apoptosis Molecular cell 29 541 551 18342602 PMC2361721
- Ozcan U Yilmaz E Ozcan L Furuhashi M Vaillancourt E Smith RO Gorgun CZ Hotamisligil GS 2006 Chemical chaperones reduce ER stress and restore glucose homeostasis in a mouse model of type 2 diabetes Science 313 1137 1140 16931765 PMC4741373
- Park SW Ozcan U 2013 Potential for therapeutic manipulation of the UPR in disease Seminars in immunopathology 35 351 373 23572207 PMC3641308
- Park SW Zhou Y Lee J Lee J Ozcan U 2010 Sarco(endo)plasmic reticulum Ca2+-ATPase 2b is a major regulator of endoplasmic reticulum stress and glucose homeostasis in obesity Proceedings of the National Academy of Sciences of the United States of America 107 19320 19325 20974941 PMC2984194
- Ron D Walter P 2007 Signal integration in the endoplasmic reticulum unfolded protein response Nature reviews Molecular cell biology 8 519 529 17565364
- Ryan KK Tremaroli V Clemmensen C Kovatcheva-Datchary P Myronovych A Karns R Wilson-Perez HE Sandoval DA Kohli R Backhed F 2014 FXR is a molecular target for the effects of vertical sleeve gastrectomy Nature 509 183 188 24670636 PMC4016120
- Williams KW Liu T Kong X Fukuda M Deng Y Berglund ED Deng Z Gao Y Liu T Sohn JW 2014 Xbp1s in Pomc Neurons Connects ER Stress with Energy Balance and Glucose Homeostasis Cell metabolism PMC4186248 25017942
Cited by
Sorted by citations
A Next Generation Connectivity Map: L1000 Platform and the First 1,000,000 Profiles
Subramanian, A., Narayan, R., Corsello, S. M., Peck, D. D., Natoli, T. E., Lu, X., Gould, J., Davis, J. F., Tubelli, A. A., Asiedu, J. K., et al. (2017) · Cell · doi:10.1016/j.cell.2017.10.049 · Cited by 3,515 · see citing works
Anti-obesity drug discovery: advances and challenges
Müller, T. D., Blüher, M., Tschöp, M. H., & DiMarchi, R. D. (2022) · Nature Reviews Drug Discovery · doi:10.1038/s41573-021-00337-8 · Cited by 1,021 · see citing works
Opportunities and challenges in phenotypic drug discovery: an industry perspective
Moffat, J. G., Vincent, F., Lee, J. A., Eder, J., & Prunotto, M. (2017) · Nature Reviews Drug Discovery · doi:10.1038/nrd.2017.111 · Cited by 939 · see citing works
Self-citationLeptin and the endocrine control of energy balance
Friedman, J. M. (2019) · Nature Metabolism · doi:10.1038/s42255-019-0095-y · Cited by 661 · see citing works
Persistent microbiome alterations modulate the rate of post-dieting weight regain
Thaiss, C. A., Itav, S., Rothschild, D., Meijer, M. T., Levy, M., Moresi, C., Dohnalová, L., Braverman, S., Rozin, S., Malitsky, S., et al. (2016) · Nature · doi:10.1038/nature20796 · Cited by 471 · see citing works
Progress and challenges in anti-obesity pharmacotherapy
Bessesen, D. H., & Van Gaal, L. F. (2018) · The Lancet Diabetes & Endocrinology · doi:10.1016/s2213-8587(17)30236-x · Cited by 347 · see citing works
Leptin and the maintenance of elevated body weight
Pan, W. W., & Myers, M. G. (2018) · Nature reviews. Neuroscience · doi:10.1038/nrn.2017.168 · Cited by 344 · see citing works
Integrative neurocircuits that control metabolism and food intake
Brüning, J. C., & Fenselau, H. (2023) · Science · doi:10.1126/science.abl7398 · Cited by 214 · see citing works
Immunologic and endocrine functions of adipose tissue: implications for kidney disease
Zhu, Q., & Scherer, P. E. (2018) · Nature Reviews Nephrology · doi:10.1038/nrneph.2017.157 · Cited by 200 · see citing works
Anti-obesity therapy: from rainbow pills to polyagonists
Müller, T. D., Clemmensen, C., Finan, B., DiMarchi, R. D., & Tschöp, M. H. (2018) · Pharmacological Reviews · doi:10.1124/pr.117.014803 · Cited by 199 · see citing works
Prediction of drug efficacy from transcriptional profiles with deep learning
Zhu, J., Wang, J., Wang, X., Gao, M., Guo, B., Gao, M., Liu, J., Yu, Y., Wang, L., Kong, W., et al. (2021) · Nature Biotechnology · doi:10.1038/s41587-021-00946-z · Cited by 193 · see citing works
Self-citationFan, N., Zhang, X., Zhao, W., Zhao, J., Luo, D., Sun, Y., Li, D., Zhao, C., Wang, Y., Zhang, H., et al. (2022) · International Journal of Biological Sciences · doi:10.7150/ijbs.73890 · Cited by 104 · see citing works
Allen, S. D., Liu, Y.-G., Kim, T., Bobbala, S., Yi, S., Zhang, X., Choi, J., & Scott, E. A. (2019) · Biomaterials Science · doi:10.1039/c8bm01224e · Cited by 95 · see citing works
Zhou, H., Ma, C., Wang, C., Gong, L., Zhang, Y., & Li, Y. (2021) · European Journal of Pharmacology · doi:10.1016/j.ejphar.2021.173976 · Cited by 73 · see citing works
Breaking the paradigm: Dr Insight empowers signature-free, enhanced drug repurposing
Chan, J., Wang, X., Turner, J. A., Baldwin, N. E., & Gu, J. (2019) · Bioinformatics · doi:10.1093/bioinformatics/btz006 · Cited by 50 · see citing works
Abu Bakar, M. H., Shariff, K. A., Tan, J. S., & Lee, L. K. (2020) · European Journal of Pharmacology · doi:10.1016/j.ejphar.2020.173371 · Cited by 51 · see citing works
(2020) · Advances in clinical chemistry · doi:10.1016/bs.acc.2019.07.012 · Cited by 46 · see citing works
Payne, N. C., Maksoud, S., Tannous, B. A., & Mazitschek, R. (2022) · Cell Chemical Biology · doi:10.1016/j.chembiol.2022.05.003 · Cited by 44 · see citing works
Self-citationElucidating the mechanisms by which disulfiram protects against obesity and metabolic syndrome
Bernier, M., Harney, D., Koay, Y. C., Diaz, A., Singh, A., Wahl, D., Pulpitel, T., Ali, A., Guiterrez, V., Mitchell, S. J., et al. (2020) · npj Aging and Mechanisms of Disease · doi:10.1038/s41514-020-0046-6 · Cited by 26 · see citing works
Resveratrol Inhibits Human Visceral Preadipocyte Proliferation and Differentiation <i>in vitro</i>
Sun, W., Yu, S., Han, H., Yuan, Q., Chen, J., & Xu, G. (2019) · Lipids · doi:10.1002/lipd.12196 · Cited by 11 · see citing works
Huang, M., Chen, L., Ma, X., & Xu, H. (2024) · Cancer Cell International · doi:10.1186/s12935-024-03542-8 · Cited by 9 · see citing works
“This could be associated with celastrol’s potential to enhance leptin sensitivity, thereby suppressing appetite [36].”
BackgroundLiu, Y., & Gong, F. (2025) · Phytotherapy Research · doi:10.1002/ptr.8415 · Cited by 6 · see citing works
- Authors
- Liu, J., Lee, J., Salazar Hernandez, M. A., Mazitschek, R., & Ozcan, U.
- Affiliations
- Boston Children's Hospital (US)
- Broad Institute (US)
- Venue
- Cell
- Publisher
- Elsevier BV
- Published
- 2015-05
- Volume
- 161
- Issue
- 5
- Pages
- 999-1011
- ISSN
- 0092-8674 (ISSN-L)
- PMC
- PMC4768733
- OpenAlex
- W1509405108
- Cited by
- 726
- References
- 4
- Citations by year
- 2026: 52 · 2025: 60 · 2024: 83 · 2023: 67 · 2022: 79 · 2021: 81 · 2020: 84 · 2019: 63 · 2018: 54 · 2017: 55 · 2016: 41 · 2015: 7
- FWCI
- 26.34
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Cell (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- American Diabetes Association
- National Institutes of Health
- National Institute of Diabetes and Digestive and Kidney Diseases (R01DK098496)
- Topics
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Regulation of Appetite and Obesity
- Health Sciences › Medicine › Pharmacology › Pharmacology and Obesity Treatment
- Health Sciences › Medicine › Complementary and alternative medicine › Natural Compounds in Disease Treatment
- Keywords
- celastrol, obesity, leptin sensitivity, leptin resistance, Tripterygium wilfordii, pentacyclic triterpenes, anti-obesity drugs, diet-induced obesity, feeding inhibition, energy expenditure, ob/ob mice
- MeSH terms
- Animals, Energy Metabolism, Glucose, Hypothalamus, Obesity, Plant Extracts, Triterpenes, Anti-Obesity Agents, Leptin, Gene Expression Profiling, Tripterygium, Mice, Pentacyclic Triterpenes
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