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Sub-nanosized vanadate hybrid clusters maintain glucose homeostasis and restore treatment response in inflammatory disease in obese mice

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Abstract

Obesity is closely related with insulin resistance and chronic inflammation. Here, we report that unsaturated lipid-modified polyoxovanadates (ULPOVs) can restrict weight gain of diet-induced obese mice and improve their glycemic control and obesity-associated inflammation. Oral administration of the sub-nanosized ULPOVs at a low dosage for 7 weeks reduces the body weight and almost normalizes the blood glucose levels of obese mice fed on a high-fat diet. ULPOV treatment increases the activity of the nuclear receptor peroxisome proliferator-activated receptor γ (PPARγ) and reduces intestinal caloric intake, which may be the main reason for blood sugar and body weight control. In addition to insulin-sensitizing, PPARγ activation induced by ULPOV treatment in obese mice with atopic dermatitis (AD) promotes the type 2 T helper (TH2) cell selective responses and therapeutic effects on immune dysregulation caused by obesity. These data suggest sub-nanosized polyoxovanadate clusters as a class of potential candidates to relieve symptoms accompanied by diet-induced obesity.

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References

  1. Furman, D.; Campisi, J.; Verdin, E.; Carrera-Bastos, P.; Targ, S.; Franceschi, C.; Ferrucci, L.; Gilroy, D. W.; Fasano, A.; Miller, G. W. et al. Chronic inflammation in the etiology of disease across the life span. Nat. Med. 2019, 25, 1822–1832.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Sakers, A.; De Siqueira, M. K.; Seale, P.; Villanueva, C. J. Adiposetissue plasticity in health and disease. Cell 2022, 185, 419–446.

    Article  CAS  PubMed  Google Scholar 

  3. Huang, X. Z.; Shi, Y. J.; Chen, H. J.; Le, R. R.; Gong, X. H.; Xu, K.; Zhu, Q. H.; Shen, F. X.; Chen, Z. M.; Gu, X. M. et al. Isoliquiritigenin prevents hyperglycemia-induced renal injuries by inhibiting inflammation and oxidative stress via SIRT1-dependent mechanism. Cell Death Dis. 2020, 11, 1040.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Priest, C.; Tontonoz, P. Inter-organ cross-talk in metabolic syndrome. Nat. Metab. 2019, 1, 1177–1188.

    Article  PubMed  Google Scholar 

  5. Netea, M. G.; Domínguez-Andrés, J.; Barreiro, L. B.; Chavakis, T.; Divangahi, M.; Fuchs, E.; Joosten, L. A. B.; van der Meer, J. W. M.; Mhlanga, M. M.; Mulder, W. J. M. et al. Defining trained immunity and its role in health and disease. Nat. Rev. Immunol. 2020, 20, 375–388.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Bookout, A. L.; de Groot, M. H. M.; Owen, B. M.; Lee, S.; Gautron, L.; Lawrence, H. L.; Ding, X. S.; Elmquist, J. K.; Takahashi, J. S.; Mangelsdorf, D. J. et al. FGF21 regulates metabolism and circadian behavior by acting on the nervous system. Nat. Med. 2013, 19, 1147–1152

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Ruderman, N. B.; Carling, D.; Prentki, M.; Cacicedo, J. M. AMPK, insulin resistance, and the metabolic syndrome. J. Clin. Invest. 2013, 123, 2764–2772.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Brautigan, D. L. Protein Ser/Thr phosphatases-the ugly ducklings of cell signalling. FEBS J. 2013, 280, 324–325.

    Article  CAS  PubMed  Google Scholar 

  9. Yang, Y.; Reid, M. A.; Hanse, E. A.; Li, H. Q.; Li, Y. D.; Ruiz, B. I.; Fan, Q.; Kong, M. SAPS3 subunit of protein phosphatase 6 is an AMPK inhibitor and controls metabolic homeostasis upon dietary challenge in male mice. Nat. Commun. 2023, 14, 1368

    Article  ADS  CAS  PubMed  PubMed Central  Google Scholar 

  10. Catrysse, L.; Maes, B.; Mehrotra, P.; Martens, A.; Hoste, E.; Martens, L.; Maueröder, C.; Remmerie, A.; Bujko, A.; Slowicka, K. et al. A20 deficiency in myeloid cells protects mice from diet-induced obesity and insulin resistance due to increased fatty acid metabolism. Cell Rep. 2021, 36, 109748

    Article  CAS  PubMed  Google Scholar 

  11. Priem, D.; van Loo, G.; Bertrand, M. J. M. A20 and cell death-driven inflammation. Trends Immunol. 2020, 41, 421–435

    Article  CAS  PubMed  Google Scholar 

  12. Francque, S.; Szabo, G.; Abdelmalek, M. F.; Byrne, C. D.; Cusi, K.; Dufour, J. F.; Roden, M.; Sacks, F.; Tacke, F. Nonalcoholic steatohepatitis: The role of peroxisome proliferator-activated receptors. Nat. Rev. Gastroenterol. Hepatol. 2021, 18, 24–39.

    Article  PubMed  Google Scholar 

  13. Montaigne, D.; Butruille, L.; Staels, B. PPAR control of metabolism and cardiovascular functions. Nat. Rev. Cardiol. 2021, 18, 809–823.

    Article  CAS  PubMed  Google Scholar 

  14. Scholtes, C.; Giguère, V. Transcriptional control of energy metabolism by nuclear receptors. Nat. Rev. Mol. Cell Biol. 2022, 23, 750–770.

    Article  CAS  PubMed  Google Scholar 

  15. Tontonoz, P.; Spiegelman, B. M. Fat and beyond: The diverse biology of PPARy. Annu. Rev. Biochem. 2008, 77, 289–312.

    Article  CAS  PubMed  Google Scholar 

  16. Odegaard, J. I.; Ricardo-Gonzalez, R. R.; Goforth, M. H.; Morel, C. R.; Subramanian, V.; Mukundan, L.; Red Eagle, A.; Vats, D.; Brombacher, F.; Ferrante, A. W. et al. Macrophage-specific PPARy controls alternative activation and improves insulin resistance. Nature 2007, 447, 1116–1120.

    Article  ADS  CAS  PubMed  PubMed Central  Google Scholar 

  17. Forman, B. M.; Tontonoz, P.; Chen, J.; Brun, R. P.; Spiegelman, B. M.; Evans, R. M. 15-Deoxy-Δ12, 14-prostaglandin J2 is a ligand for the adipocyte determination factor PPARγ. Cell 1995, 83, 803–812

    Article  CAS  PubMed  Google Scholar 

  18. Jiang, C. Y.; Ting, A. T.; Seed, B. PPAR-y agonists inhibit production of monocyte inflammatory cytokines. Nature 1998, 391, 82–86.

    Article  ADS  CAS  PubMed  Google Scholar 

  19. Wang, L. M.; Waltenberger, B.; Pferschy-Wenzig, E. M.; Blunder, M.; Liu, X.; Malainer, C.; Blazevic, T.; Schwaiger, S.; Rollinger, J. M.; Heiss, E. H. et al. Natural product agonists of peroxisome proliferator-activated receptor gamma (PPARy): A review. Biochem. Pharmacol. 2014, 92, 73–89.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Wu, Y. L.; Huang, M. L.; Zhao, P.; Yang, X. D. Vnaayyl acetylacetonate upregulates PPARy and adiponectin expression in differentiated rat adipocytes. J. Biol. Inorg. Chem. 2013, 18, 623–631.

    Article  CAS  PubMed  Google Scholar 

  21. Dong, Y. Q.; Stewart, T.; Zhang, Y.; Shi, M.; Tan, C.; Li, X.; Yuan, L.; Mehrotra, A.; Zhang, J.; Yang, X. D. Anti- diabetic vanadyl complexes reduced Alzheimer’s disease pathology independent of amyloid plaque deposition. Sci. China Life Sci. 2019, 62, 126–139.

    Article  CAS  PubMed  Google Scholar 

  22. Aureliano, M.; Gumerova, N. I.; Sciortino, G.; Garribba, E.; Rompel, A.; Crans, D. C. Polyoxovanadates with emerging biomedical activities. Coord. Chem. Rev. 2021, 447, 214143.

    Article  CAS  Google Scholar 

  23. Chen, K.; Jia, H. L.; Liu, Y.; Yin, P. C.; Wei, Y. G. Insulin-sensitizing activity of sub-nanoscaled polyalkoxyvanadate clusters. Adv. Biosyst. 2020, 4, 1900281.

    Article  CAS  Google Scholar 

  24. Chen, K.; Liu, S. Q.; Zhang, Q. Y. Degradation and detection of endocrine disruptors by laccase-mimetic polyoxometalates. Front. Chem. 2022, 10, 854045.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Zang, D. J.; Huang, Y. C.; Li, Q.; Tang, Y. J.; Wei, Y. G. Cu dendrites induced by the Anderson-type polyoxometalate NiMo6O24 as a promising electrocatalyst for enhanced hydrogen evolution. Appl. Catal. B: Environ. 2019, 249, 163–171.

    Article  CAS  Google Scholar 

  26. Wei, Z. Y.; Ru, S.; Zhao, Q. X.; Yu, H.; Zhang, G.; Wei, Y. G. Highly efficient and practical aerobic oxidation of alcohols by inorganic-ligand supported copper catalysis. Green Chem. 2019, 21, 4069–4075.

    Article  CAS  Google Scholar 

  27. Xia, Z. N.; Wang, L. B.; Zhang, Q.; Li, F. Y.; Xu, L. Fast degradation of phenol over porphyrin-polyoxometalate composite photocatalysts under visible light. Potyooomatalates 2022, 1, 9140001.

    Google Scholar 

  28. Kong, X. P.; Wan, G. F.; Li, B.; Wu, L. X. Recent advances of polyoxometalates in multi-functional imaging and photothermal therapy. J. Mater. Chem. B 2020, 8, 8189–8206.

    Article  CAS  PubMed  Google Scholar 

  29. Li, X. P.; Liu, S. Q.; Yin, P. C.; Chen, K. Enhanced immune responses by virus-mimetic polymeric nanostructures against infectious diseases. Front. Immunol. 2022, 12, 804416.

    Article  PubMed  PubMed Central  Google Scholar 

  30. Li, X. P.; He, X. F.; He, D. R.; Liu, Y.; Chen, K.; Yin, P. C. A polymeric co-assembly of subunit vaccine with polyoxometalates induces enhanced immune responses. Nano Res. 2022, 15, 4175–4180.

    Article  ADS  CAS  PubMed  Google Scholar 

  31. Chen, K.; Liu, Y.; Li, M.; Liu, L.; Yu, Q.; Wu, L. Amelioration of enteric dysbiosis by polyoxotungstates in mice gut. J. Inorg. Biochem. 2022, 226, 111654.

    Article  CAS  PubMed  Google Scholar 

  32. Azambuja, F. D.; Moons, J.; Parac-Vogt, T. N. The dawn of metal-oxo clusters as artificial proteases: From discovery to the present and beyond. Acc. Chem. Res. 2021, 54, 1673–1684.

    Article  CAS  PubMed  Google Scholar 

  33. Chen, J. J.; Symes, M. D.; Cronin, L. Highly reduced and protonated aqueous solutions of [P2W18O62]6− for on-demand hydrogen generation and energy storage. Nat. Chem. 2018, 10, 1042–1047.

    Article  CAS  PubMed  Google Scholar 

  34. Liu, L.; Wu, Z. C.; Zheng, Z.; Zhou, Q. J.; Chen, K.; Yin, P. C. Polymerization-induced microphase separation of polymer-polyoxometalate nanocomposites for anhydrous solid state electrolytes. Chin. Chem. Lett. 2022, 33, 4326–4330.

    Article  CAS  Google Scholar 

  35. Chen, K.; Liu, S. Q.; Zhu, W.; Yin, P. C. Surface engineering promoted insulin-sensitizing activities of sub-nanoscale vanadate clusters through regulated pharmacokinetics and bioavailability. Small 2022, 18, 2203957.

    Article  CAS  Google Scholar 

  36. Chen, K.; Dai, G. Y.; Liu, S. Q.; Wei, Y. G. Reducing obesity and inflammation in mice with organically-derivatized polyoxovanadate clusters. Chin. Chem. Lett. 2023, 34, 107638.

    Article  CAS  Google Scholar 

  37. Kennedy, A.; Martinez, K.; Chuang, C. C.; LaPoint, K.; McIntosh, M. Saturated fatty acid-mediated inflammation and insulin resistance in adipose tissue: Mechanisms of action and implications. J. Nutr. 2009, 139, 1–4.

    Article  CAS  PubMed  Google Scholar 

  38. Morstein, J.; Capecchi, A.; Hinnah, K.; Park, B.; Petit-Jacques, J.; Van Lehn, R. C.; Reymond, J. L.; Trauner, D. Medium- chain lipid conjugation facilitates cell-permeability and bioactivity. J. Am. Chem. Soc. 2022, 144, 18532–18544.

    Article  CAS  PubMed  Google Scholar 

  39. Chen, K.; Bayaguud, A.; Li, H.; Chu, Y.; Zhang, H. C.; Jia, H. L.; Zhang, B. F.; Xiao, Z. C.; Wu, P. F.; Liu, T. B. et al. Improved peroxidase-mimic property: Sustainable, high-efficiency interfacial catalysis with H2O2 on the surface of vesicles of hexavanadate-organic hybrid surfactants. Nano Res. 2018, 11, 1313–1321.

    Article  CAS  Google Scholar 

  40. Chen, Q.; Goshorn, D. P.; Scholes, C. P.; Tan, X. L.; Zubieta, J. Coordination compounds of polyoxovanadates with a hexametalate core Chemical and structural characterization of [VV6O13[(OCH2)3CR]2]2−, [VV6O11(OH)2[(OCH2)3CR]2], [VIV4VV2O9(OH)4[(OCH2)3CR]2]2−, and [VIV6O7(OH)6](OCH2)3CR]2]2. J. Am. Chem. Soc. 1992, 114, 4667–4681

    Article  CAS  Google Scholar 

  41. Papsdorf, K.; Miklas, J. W.; Hosseini, A.; Cabruja, M.; Morrow, C. S.; Savini, M.; Yu, Y.; Silva-Garcia, C. G.; Haseley, N. R.; Murphy, L. M. et al. Lipid droplets and peroxisomes are co-regulated to drive lifespan extension in response to mono-unsaturated fatty acids. Nat. Cell Biol. 2023, 25, 672–684.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. Palomer, X.; Pizarro-Delgado, J.; Barroso, E.; Vázquez-Carrera, M. Palmitic and oleic acid: The Yin and Yang of fatty acids in type 2 diabetes mellitus. Trends Endocrinol. Metab. 2018, 29, 178–190.

    Article  CAS  PubMed  Google Scholar 

  43. Davies, M. J.; D’Alessio, D. A.; Fradkin, J.; Kernan, W. N.; Mathieu, C.; Mingrone, G.; Rossing, P.; Tsapas, A.; Wexler, D. J.; Buse, J. B. Management of hyperglycaemia in type 2 diabetes, 2018. A consensus report by the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD). Diabetologia 2018, 61, 2461–2498.

    Article  PubMed  Google Scholar 

  44. Ji, Y. D.; Luo, Z. L.; Gao, H.; Dos Reis, F. C. G.; Bandyopadhyay, G.; Jin, Z. M.; Manda, K. A.; Isaac, R.; Yang, M. X.; Fu, W. X. et al. Hepatocyte-derived exosomes from early onset obese mice promote insulin sensitivity through miR-3075. Nat. Metab. 2021, 3, 1163–1174.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  45. Ohno, H.; Shinoda, K.; Spiegelman, B. M.; Kajimura, S. PPARγagonists induce a white-to-brown fat conversion through stabilization of PRDM16 protein. Cell Metab. 2012, 15, 395–404

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  46. Bapat, S. P.; Whitty, C.; Mowery, C. T.; Liang, Y. Q.; Yoo, A.; Jiang, Z. W.; Peters, M. C.; Zhang, L. J.; Vogel, I.; Zhou, C. et al. Obesity alters pathology and treatment response in inflammatory disease. Nature 2022, 604, 337–342.

    Article  ADS  CAS  PubMed  PubMed Central  Google Scholar 

  47. Li, Z. A.; Luo, L. L.; Yu, W. X.; Li, P.; Ou, D. F.; Liu, J.; Ma, H. H.; Sun, Q. H.; Liang, A. B.; Huang, C. et al. PPARyphase separates with RXRa at PPREs to regulate target gene expression. Cell Discov. 2022, 8, 37

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  48. Henriksson, J.; Chen, X.; Gomes, T.; Ullah, U.; Meyer, K. B.; Miragaia, R.; Duddy, G.; Pramanik, J.; Yusa, K.; Lahesmaa, R. et al. Genome-wide CRISPR screens in T helper cells reveal pervasive crosstalk between activation and differentiation. Cell 2019, 176, 882–896.e18.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  49. Nobs, S. P.; Natali, S.; Pohlmeier, L.; Okreglicka, K.; Schneider, C.; Kurrer, M.; Sallusto, F.; Kopf, M. PPARy in dendritic cells and T cells drives pathogenic type-2 effector responses in lung inflammation. J. Exp. Med. 2017, 214, 3015–3035

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  50. Oishi, K.; Uchida, D.; Ishida, N. Circadian expression of FGF21 is induced by PPARa activation in the mouse liver. FEBS Lett. 2008, 582, 3639–3642

    Article  CAS  PubMed  Google Scholar 

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Acknowledgements

This work was financially supported by the National Natural Science Foundation of China (No. 22101086), the Natural Science Foundation of Guangdong Province (No. 2021A1515010271), and the Guangzhou Basic and Applied Basic Research Project (No. 202201010052).

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Authors and Affiliations

  1. South China Advanced Institute for Soft Matter Science and Technology, School of Emergent Soft Matter, South China University of Technology, Guangzhou, 510641, China

    Kun Chen, Shengqiu Liu & Yujun Wei

  2. Guangdong Provincial Key Laboratory of Technique and Equipment for Macromolecular Advanced Manufacturing, South China University of Technology, Guangzhou, 510641, China

    Kun Chen

  3. Guangdong Provincial Key Laboratory of Functional and Intelligent Hybrid Materials and Devices, South China University of Technology, Guangzhou, 510641, China

    Kun Chen

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  1. Kun Chen
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Correspondence to Kun Chen.

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Sub-nanosized vanadate hybrid clusters maintain glucose homeostasis and restore treatment response in inflammatory disease in obese mice

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Chen, K., Liu, S. & Wei, Y. Sub-nanosized vanadate hybrid clusters maintain glucose homeostasis and restore treatment response in inflammatory disease in obese mice. Nano Res. 17, 1818–1826 (2024). https://doi.org/10.1007/s12274-023-6366-7

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