DOI QR코드

DOI QR Code

Specialized Proresolving Mediators for Therapeutic Interventions Targeting Metabolic and Inflammatory Disorders

  • Han, Yong-Hyun (Laboratory of Pathology and Physiology, College of Pharmacy, Kangwon National University) ;
  • Lee, Kyeongjin (Laboratory of Pathology and Physiology, College of Pharmacy, Kangwon National University) ;
  • Saha, Abhirup (College of Pharmacy, Seoul National University) ;
  • Han, Juhyeong (College of Pharmacy, Seoul National University) ;
  • Choi, Haena (College of Pharmacy, Seoul National University) ;
  • Noh, Minsoo (College of Pharmacy, Seoul National University) ;
  • Lee, Yun-Hee (College of Pharmacy, Seoul National University) ;
  • Lee, Mi-Ock (College of Pharmacy, Seoul National University)
  • Received : 2021.05.18
  • Accepted : 2021.06.08
  • Published : 2021.09.01

Abstract

Uncontrolled inflammation is considered the pathophysiological basis of many prevalent metabolic disorders, such as nonalcoholic fatty liver disease, diabetes, obesity, and neurodegenerative diseases. The inflammatory response is a self-limiting process that produces a superfamily of chemical mediators, called specialized proresolving mediators (SPMs). SPMs include the ω-3-derived family of molecules, such as resolvins, protectins, and maresins, as well as arachidonic acid-derived (ω-6) lipoxins that stimulate and promote resolution of inflammation, clearance of microbes, and alleviation of pain and promote tissue regeneration via novel mechanisms. SPMs function by binding and activating G protein-coupled receptors, such as FPR2/ALX, GPR32, and ERV1, and nuclear orphan receptors, such as RORα. Recently, several studies reported that SPMs have the potential to attenuate lipid metabolism disorders. However, the understanding of pharmacological aspects of SPMs, including tissue-specific biosynthesis, and specific SPM receptors and signaling pathways, is currently limited. Here, we summarize recent advances in the role of SPMs in resolution of inflammatory diseases with metabolic disorders, such as nonalcoholic fatty liver disease and obesity, obtained from preclinical animal studies. In addition, the known SPM receptors and their intracellular signaling are reviewed as targets of resolution of inflammation, and the currently available information on the therapeutic effects of major SPMs for metabolic disorders is summarized.

Keywords

Acknowledgement

This study was supported by a grant from the National Research Foundation of Korea (NRF) (2021R1C1C1004023 to Y.H.H.; NRF-2019R1C1C1002014 to Y.H.L.; 2017R1A2B3011870 to M.O.L., and 2018R1A5A2024425 to Y.H.L. and M.O.L.) and 2020 Research Grant from Kangwon National University.

References

  1. Araujo, A. C., Wheelock, C. E. and Haeggstrom, J. Z. (2018) The eicosanoids, redox-regulated lipid mediators in immunometabolic disorders. Antioxid. Redox Signal. 29, 275-296. https://doi.org/10.1089/ars.2017.7332
  2. Arita, M., Bianchini, F., Aliberti, J., Sher, A., Chiang, N., Hong, S., Yang, R., Petasis, N. A. and Serhan, C. N. (2005) Stereochemical assignment, antiinflammatory properties, and receptor for the omega-3 lipid mediator resolvin E1. J. Exp. Med. 201, 713-722. https://doi.org/10.1084/jem.20042031
  3. Arita, M., Oh, S. F., Chonan, T., Hong, S., Elangovan, S., Sun, Y. P., Uddin, J., Petasis, N. A. and Serhan, C. N. (2006) Metabolic inactivation of resolvin E1 and stabilization of its anti-inflammatory actions. J. Biol. Chem. 281, 22847-22854. https://doi.org/10.1074/jbc.M603766200
  4. Arita, M., Ohira, T., Sun, Y. P., Elangovan, S., Chiang, N. and Serhan, C. N. (2007) Resolvin E1 selectively interacts with leukotriene B4 receptor BLT1 and ChemR23 to regulate inflammation. J. Immunol. 178, 3912-3917. https://doi.org/10.4049/jimmunol.178.6.3912
  5. Bang, S., Xie, Y. K., Zhang, Z. J., Wang, Z., Xu, Z. Z. and Ji, R. R. (2018) GPR37 regulates macrophage phagocytosis and resolution of inflammatory pain. J. Clin. Invest. 128, 3568-3582. https://doi.org/10.1172/JCI99888
  6. Borgeson, E., Johnson, A. M., Lee, Y. S., Till, A., Syed, G. H., Ali-Shah, S. T., Guiry, P. J., Dalli, J., Colas, R. A., Serhan, C. N., Sharma, K. and Godson, C. (2015) Lipoxin A4 attenuates obesity-induced adipose inflammation and associated liver and kidney disease. Cell Metab. 22, 125-137. https://doi.org/10.1016/j.cmet.2015.05.003
  7. Borgeson, E., McGillicuddy, F. C., Harford, K. A., Corrigan, N., Higgins, D. F., Maderna, P., Roche, H. M. and Godson, C. (2012) Lipoxin A4 attenuates adipose inflammation. FASEB J. 26, 4287-4294. https://doi.org/10.1096/fj.12-208249
  8. Buckley, C. D., Gilroy, D. W. and Serhan, C. N. (2014) Proresolving lipid mediators and mechanisms in the resolution of acute inflammation. Immunity 40, 315-327. https://doi.org/10.1016/j.immuni.2014.02.009
  9. Calandria, J. M., Asatryan, A., Balaszczuk, V., Knott, E. J., Jun, B. K., Mukherjee, P. K., Belayev, L. and Bazan, N. G. (2015a) NPD1-mediated stereoselective regulation of BIRC3 expression through cREL is decisive for neural cell survival. Cell Death Differ. 22, 1363-1377. https://doi.org/10.1038/cdd.2014.233
  10. Calandria, J. M., Sharp, M. W. and Bazan, N. G. (2015b) The docosanoid neuroprotectin D1 induces TH-positive neuronal survival in a cellular model of Parkinson's disease. Cell. Mol. Neurobiol. 35, 1127-1136. https://doi.org/10.1007/s10571-015-0206-6
  11. Chiang, N., Barnaeva, E., Hu, X., Marugan, J., Southall, N., Ferrer, M. and Serhan, C. N. (2019a) Identification of chemotype agonists for human resolvin D1 receptor DRV1 with pro-resolving functions. Cell Chem. Biol. 26, 244-254.e4. https://doi.org/10.1016/j.chembiol.2018.10.023
  12. Chiang, N., Libreros, S., Norris, P. C., de la Rosa, X. and Serhan, C. N. (2019b) Maresin 1 activates LGR6 receptor promoting phagocyte immunoresolvent functions. J. Clin. Invest. 129, 5294-5311. https://doi.org/10.1172/JCI129448
  13. Chiang, N. and Serhan, C. N. (2017) Structural elucidation and physiologic functions of specialized pro-resolving mediators and their receptors. Mol. Aspects Med. 58, 114-129. https://doi.org/10.1016/j.mam.2017.03.005
  14. Claria, J., Dalli, J., Yacoubian, S., Gao, F. and Serhan, C. N. (2012) Resolvin D1 and resolvin D2 govern local inflammatory tone in obese fat. J. Immunol. 189, 2597-2605. https://doi.org/10.4049/jimmunol.1201272
  15. Claria, J., Nguyen, B. T., Madenci, A. L., Ozaki, C. K. and Serhan, C. N. (2013) Diversity of lipid mediators in human adipose tissue depots. Am. J. Physiol. Cell Physiol. 304, C1141-C1149. https://doi.org/10.1152/ajpcell.00351.2012
  16. Dalli, J. and Serhan, C. N. (2012) Specific lipid mediator signatures of human phagocytes: microparticles stimulate macrophage efferocytosis and pro-resolving mediators. Blood 120, e60-e72. https://doi.org/10.1182/blood.V120.21.60.60
  17. Enomoto, N., Ikejima, K., Yamashina, S., Enomoto, A., Nishiura, T., Nishimura, T., Brenner, D. A., Schemmer, P., Bradford, B. U., Rivera, C. A., Zhong, Z. and Thurman, R. G. (2000) Kupffer cell-derived prostaglandin E(2) is involved in alcohol-induced fat accumulation in rat liver. Am. J. Physiol. Gastrointest. Liver Physiol. 279, G100-G106. https://doi.org/10.1152/ajpgi.2000.279.1.G100
  18. Fredman, G., Hellmann, J., Proto, J. D., Kuriakose, G., Colas, R. A., Dorweiler, B., Connolly, E. S., Solomon, R., Jones, D. M., Heyer, E. J., Spite, M. and Tabas, I. (2016) An imbalance between specialized pro-resolving lipid mediators and pro-inflammatory leukotrienes promotes instability of atherosclerotic plaques. Nat. Commun. 7, 12859. https://doi.org/10.1038/ncomms12859
  19. Fredman, G. and Tabas, I. (2017) Boosting inflammation resolution in atherosclerosis: the next frontier for therapy. Am. J. Pathol. 187, 1211-1221. https://doi.org/10.1016/j.ajpath.2017.01.018
  20. Ghandour, R. A., Colson, C., Giroud, M., Maurer, S., Rekima, S., Ailhaud, G., Klingenspor, M., Amri, E. Z. and Pisani, D. F. (2018) Impact of dietary omega3 polyunsaturated fatty acid supplementation on brown and brite adipocyte function. J. Lipid Res. 59, 452-461. https://doi.org/10.1194/jlr.M081091
  21. Gonzalez-Periz, A., Horrillo, R., Ferre, N., Gronert, K., Dong, B., Moran-Salvador, E., Titos, E., Martinez-Clemente, M., Lopez-Parra, M., Arroyo, V. and Claria, J. (2009) Obesity-induced insulin resistance and hepatic steatosis are alleviated by omega-3 fatty acids: a role for resolvins and protectins. FASEB J. 23, 1946-1957. https://doi.org/10.1096/fj.08-125674
  22. Gonzalez-Periz, A., Planaguma, A., Gronert, K., Miquel, R., Lopez-Parra, M., Titos, E., Horrillo, R., Ferre, N., Deulofeu, R., Arroyo, V., Rodes, J. and Claria, J. (2006) Docosahexaenoic acid (DHA) blunts liver injury by conversion to protective lipid mediators: protectin D1 and 17S-hydroxy-DHA. FASEB J. 20, 2537-2539. https://doi.org/10.1096/fj.06-6250fje
  23. Han, Y. H., Kim, H. J., Na, H., Nam, M. W., Kim, J. Y., Kim, J. S., Koo, S. H. and Lee, M. O. (2017) RORα induces KLF4-mediated M2 polarization in the liver macrophages that protect against nonalcoholic steatohepatitis. Cell Rep. 20, 124-135. https://doi.org/10.1016/j.celrep.2017.06.017
  24. Han, Y. H., Shin, K. O., Kim, J. Y., Khadka, D. B., Kim, H. J., Lee, Y. M., Cho, W. J., Cha, J. Y., Lee, B. J. and Lee, M. O. (2019) A maresin 1/RORα/12-lipoxygenase autoregulatory circuit prevents inflammation and progression of nonalcoholic steatohepatitis. J. Clin. Invest. 129, 1684-1698. https://doi.org/10.1172/JCI124219
  25. Hellmann, J., Tang, Y., Kosuri, M., Bhatnagar, A. and Spite, M. (2011) Resolvin D1 decreases adipose tissue macrophage accumulation and improves insulin sensitivity in obese-diabetic mice. FASEB J. 25, 2399-2407. https://doi.org/10.1096/fj.10-178657
  26. Holzer, G., Markov, G. V. and Laudet, V. (2017) Evolution of nuclear receptors and ligand signaling: toward a soft key-lock model? Curr. Top. Dev. Biol. 125, 1-38. https://doi.org/10.1016/bs.ctdb.2017.02.003
  27. Horrillo, R., Gonzalez-Periz, A., Martinez-Clemente, M., Lopez-Parra, M., Ferre, N., Titos, E., Moran-Salvador, E., Deulofeu, R., Arroyo, V. and Claria, J. (2010) 5-lipoxygenase activating protein signals adipose tissue inflammation and lipid dysfunction in experimental obesity. J. Immunol. 184, 3978-3987. https://doi.org/10.4049/jimmunol.0901355
  28. Jung, T. W., Kim, H. C., Abd El-Aty, A. M. and Jeong, J. H. (2018) Maresin 1 attenuates NAFLD by suppression of endoplasmic reticulum stress via AMPK-SERCA2b pathway. J. Biol. Chem. 293, 3981-3988. https://doi.org/10.1074/jbc.RA117.000885
  29. Koyama, Y. and Brenner, D. A. (2017) Liver inflammation and fibrosis. J. Clin. Invest. 127, 55-64. https://doi.org/10.1172/JCI88881
  30. Krishnamoorthy, S., Recchiuti, A., Chiang, N., Fredman, G. and Serhan, C. N. (2012) Resolvin D1 receptor stereoselectivity and regulation of inflammation and proresolving microRNAs. Am. J. Pathol. 180, 2018-2027. https://doi.org/10.1016/j.ajpath.2012.01.028
  31. Kulterer, O. C., Niederstaetter, L., Herz, C. T., Haug, A. R., Bileck, A., Pils, D., Kautzky-Willer, A., Gerner, C. and Kiefer, F. W. (2020) The presence of active brown adipose tissue determines cold-induced energy expenditure and oxylipin profiles in humans. J. Clin. Endocrinol. Metab. 105, dgaa183.
  32. Kuang, H., Hua, X., Zhou, J. and Yang, R. (2016) Resolvin D1 and E1 alleviate the progress of hepatitis toward liver cancer in long-term concanavalin A-induced mice through inhibition of NF-κB activity. Oncol. Rep. 35, 307-317. https://doi.org/10.3892/or.2015.4389
  33. Laiglesia, L. M., Lorente-Cebrian, S., Lopez-Yoldi, M., Lanas, R., Sainz, N., Martinez, J. A. and Moreno-Aliaga, M. J. (2018a) Maresin 1 inhibits TNF-alpha-induced lipolysis and autophagy in 3T3-L1 adipocytes. J. Cell. Physiol. 233, 2238-2246. https://doi.org/10.1002/jcp.26096
  34. Laiglesia, L. M., Lorente-Cebrian, S., Martinez-Fernandez, L., Sainz, N., Prieto-Hontoria, P. L., Burrell, M. A., Rodriguez-Ortigosa, C. M., Martinez, J. A. and Moreno-Aliaga, M. J. (2018b) Maresin 1 mitigates liver steatosis in ob/ob and diet-induced obese mice. Int. J. Obes. (Lond.) 42, 572-579. https://doi.org/10.1038/ijo.2017.226
  35. Leon, I. C., Quesada-Vazquez, S., Sainz, N., Guruceaga, E., Escote, X. and Moreno-Aliaga, M. J. (2020) Effects of Maresin 1 (MaR1) on colonic inflammation and gut dysbiosis in diet-induced obese mice. Microorganisms 8, 1156. https://doi.org/10.3390/microorganisms8081156
  36. Lumeng, C. N. and Saltiel, A. R. (2011) Inflammatory links between obesity and metabolic disease. J. Clin. Invest. 121, 2111-2117. https://doi.org/10.1172/JCI57132
  37. Li, J., Deng, X., Bai, T., Wang, S., Jiang, Q. and Xu, K. (2020) Resolvin D1 mitigates non-alcoholic steatohepatitis by suppressing the TLR4-MyD88-mediated NF-κB and MAPK pathways and activating the Nrf2 pathway in mice. Int. Immunopharmacol. 88, 106961. https://doi.org/10.1016/j.intimp.2020.106961
  38. Liao, Z., Dong, J., Wu, W., Yang, T., Wang, T., Guo, L., Chen, L., Xu, D. and Wen, F. (2012) Resolvin D1 attenuates inflammation in lipopolysaccharide-induced acute lung injury through a process involving the PPARγ/NF-κB pathway. Respir. Res. 13, 110. https://doi.org/10.1186/1465-9921-13-110
  39. Lopes, J. P., Morato, X., Souza, C., Pinhal, C., Machado, N. J., Canas, P. M., Silva, H. B., Stagljar, I., Gandia, J., Fernandez-Duenas, V., Lujan R., Cunha, R. A. and Ciruela, F. (2015) The role of parkinson's disease-associated receptor GPR37 in the hippocampus: functional interplay with the adenosinergic system. J. Neurochem. 134, 135-146. https://doi.org/10.1111/jnc.13109
  40. Lukiw, W. J., Cui, J. G., Marcheselli, V. L., Bodker, M., Botkjaer, A., Gotlinger, K., Serhan, C. N. and Bazan, N. G. (2005) A role for docosahexaenoic acid-derived neuroprotectin D1 in neural cell survival and Alzheimer disease. J. Clin. Invest. 115, 2774-2783. https://doi.org/10.1172/JCI25420
  41. Martinez-Clemente, M., Ferre, N., Gonzalez-Periz, A., Lopez-Parra, M., Horrillo, R., Titos, E., Moran-Salvador, E., Miquel, R., Arroyo, V., Funk, C. D. and Claria, J. (2010) 5-lipoxygenase deficiency reduces hepatic inflammation and tumor necrosis factor alpha-induced hepatocyte damage in hyperlipidemia-prone ApoE-null mice. Hepatology 51, 817-827. https://doi.org/10.1002/hep.23463
  42. Martinez-Fernandez, L., Gonzalez-Muniesa, P., Laiglesia, L. M., Sainz, N., Prieto-Hontoria, P. L., Escote, X., Odriozola, L., Corrales, F. J., Arbones-Mainar, J. M., Martinez, J. A. and Moreno-Aliaga, M. J. (2017) Maresin 1 improves insulin sensitivity and attenuates adipose tissue inflammation in ob/ob and diet-induced obese mice. FASEB J. 31, 2135-2145. https://doi.org/10.1096/fj.201600859R
  43. Martinez-Fernandez, L., Gonzalez-Muniesa, P., Sainz, N., Escote, X., Martinez, J. A., Arbones-Mainar, J. M. and Moreno-Aliaga, M. J. (2020) Maresin 1 regulates insulin signaling in human adipocytes as well as in adipose tissue and muscle of lean and obese mice. J. Physiol. Biochem. 77, 167-173. .
  44. Martinez-Fernandez, L., Gonzalez-Muniesa, P., Sainz, N., Laiglesia, L. M., Escote, X., Martinez, J. A. and Moreno-Aliaga, M. J. (2019) Maresin 1 regulates hepatic FGF21 in diet-induced obese mice and in cultured hepatocytes. Mol. Nutr. Food Res. 63, e1900358.
  45. Neuhofer, A., Zeyda, M., Mascher, D., Itariu, B. K., Murano, I., Leitner, L., Hochbrugger, E. E., Fraisl, P., Cinti, S., Serhan, C. N. and Stulnig, T. M. (2013) Impaired local production of proresolving lipid mediators in obesity and 17-HDHA as a potential treatment for obesity-associated inflammation. Diabetes 62, 1945-1956. https://doi.org/10.2337/db12-0828
  46. Neuschwander-Tetri, B. A. (2020) Therapeutic landscape for NAFLD in 2020. Gastroenterology 158, 1984-1998.e3. https://doi.org/10.1053/j.gastro.2020.01.051
  47. Oh, D. Y., Talukdar, S., Bae, E. J., Imamura, T., Morinaga, H., Fan, W., Li, P., Lu, W.J., Watkins, S. M. and Olefsky, J. M. (2010) GPR120 is an omega-3 fatty acid receptor mediating potent anti-inflammatory and insulin-sensitizing effects. Cell 142, 687-698. https://doi.org/10.1016/j.cell.2010.07.041
  48. Orr, S. K., Colas, R. A., Dalli, J., Chiang, N. and Serhan, C. N. (2015) Proresolving actions of a new resolvin D1 analog mimetic qualifies as an immunoresolvent. Am. J. Physiol. Lung Cell. Mol. Physiol. 308, L904-L911. https://doi.org/10.1152/ajplung.00370.2014
  49. Pascoal, L. B., Bombassaro, B., Ramalho, A. F., Coope, A., Moura, R. F., Correa-da-Silva, F., Ignacio-Souza, L., Razolli, D., de Oliveira, D., Catharino, R. and Velloso, L. A. (2017) Resolvin RvD2 reduces hypothalamic inflammation and rescues mice from diet-induced obesity. J. Neuroinflammation 14, 5. https://doi.org/10.1186/s12974-016-0777-2
  50. Pal, A., Al-Shaer, A. E., Guesdon, W., Torres, M. J., Armstrong, M., Quinn, K., Davis, T., Reisdorph, N., Neufer, P. D., Spangenburg, E. E., Carroll, I., Bazinet, R. P., Halade, G. V., Claria, J. and Shaikh, S. R. (2020) Resolvin E1 derived from eicosapentaenoic acid prevents hyperinsulinemia and hyperglycemia in a host genetic manner. FASEB J. 34, 10640-10656. https://doi.org/10.1096/fj.202000830R
  51. Park, J., Langmead, C. J. and Riddy, D. M. (2020) New advances in targeting the resolution of inflammation: implications for specialized pro-resolving mediator GPCR drug discovery. ACS Pharmacol. Transl. Sci. 3, 88-106. https://doi.org/10.1021/acsptsci.9b00075
  52. Piao, S., Du, W., Wei, Y., Yang, Y., Feng, X. and Bai, L. (2020) Protectin DX attenuates IL-1beta-induced inflammation via the AMPK/NF-kappaB pathway in chondrocytes and ameliorates osteoarthritis progression in a rat model. Int. Immunopharmacol. 78, 106043. https://doi.org/10.1016/j.intimp.2019.106043
  53. Puri, P., Baillie, R. A., Wiest, M. M., Mirshahi, F., Choudhury, J., Cheung, O., Sargeant, C., Contos, M. J. and Sanyal, A. J. (2007) A lipidomic analysis of nonalcoholic fatty liver disease. Hepatology 46, 1081-1090. https://doi.org/10.1002/hep.21763
  54. Puri, P., Wiest, M. M., Cheung, O., Mirshahi, F., Sargeant, C., Min, H. K., Contos, M. J., Sterling, R. K., Fuchs, M., Zhou, H., Watkins, S. M. and Sanyal, A. J. (2009) The plasma lipidomic signature of nonalcoholic steatohepatitis. Hepatology 50, 1827-1838. https://doi.org/10.1002/hep.23229
  55. Qiu, H., Gabrielsen, A., Agardh, H. E., Wan, M., Wetterholm, A., Wong, C. H., Hedin, U., Swedenborg, J., Hansson, G. K., Samuelsson, B., Paulsson-Berne, G. and Haeggstrom, J. Z. (2006) Expression of 5-lipoxygenase and leukotriene A4 hydrolase in human atherosclerotic lesions correlates with symptoms of plaque instability. Proc. Natl. Acad. Sci. U.S.A. 103, 8161-8166. https://doi.org/10.1073/pnas.0602414103
  56. Rius, B., Duran-Guell, M., Flores-Costa, R., Lopez-Vicario, C., Lopategi, A., Alcaraz-Quiles, J., Casulleras, M., Lozano, J. J., Titos, E. and Claria, J. (2017) The specialized proresolving lipid mediator maresin 1 protects hepatocytes from lipotoxic and hypoxia-induced endoplasmic reticulum stress. FASEB J. 31, 5384-5398. https://doi.org/10.1096/fj.201700394R
  57. Rius, B., Titos, E., Moran-Salvador, E., Lopez-Vicario, C., Garcia-Alonso, V., Gonzalez-Periz, A., Arroyo, V. and Claria, J. (2014) Resolvin D1 primes the resolution process initiated by calorie restriction in obesity-induced steatohepatitis. FASEB J. 28, 836-848. https://doi.org/10.1096/fj.13-235614
  58. Schmid, M., Gemperle, C., Rimann, N. and Hersberger, M. (2016) Resolvin D1 polarizes primary human macrophages toward a proresolution phenotype through GPR32. J. Immunol. 196, 3429-3437. https://doi.org/10.4049/jimmunol.1501701
  59. Serhan, C. N. (2017) Discovery of specialized pro-resolving mediators marks the dawn of resolution physiology and pharmacology. Mol. Aspects Med. 58, 1-11. https://doi.org/10.1016/j.mam.2017.03.001
  60. Serhan, C. N., Clish, C. B., Brannon, J., Colgan, S. P., Chiang, N. and Gronert, K. (2000) Novel functional sets of lipid-derived mediators with antiinflammatory actions generated from omega-3 fatty acids via cyclooxygenase 2-nonsteroidal antiinflammatory drugs and transcellular processing. J. Exp. Med. 192, 1197-1204. https://doi.org/10.1084/jem.192.8.1197
  61. Sima, C., Montero, E., Nguyen, D., Freire, M., Norris, P., Serhan, C. N. and Van Dyke, T. E. (2018) Author correction: ERV1 overexpression in myeloid cells protects against high fat diet induced obesity and glucose intolerance. Sci. Rep. 8, 4143. https://doi.org/10.1038/s41598-018-22520-5
  62. Spanbroek, R., Grabner, R., Lotzer, K., Hildner, M., Urbach, A., Ruhling, K., Moos, M. P., Kaiser, B., Cohnert, T. U., Wahlers, T., Zieske, A., Plenz, G., Robenek, H., Salbach, P., Kuhn, H., Radmark, O., Samuelsson, B. and Habenicht, A. J. (2003) Expanding expression of the 5-lipoxygenase pathway within the arterial wall during human atherogenesis. Proc. Natl. Acad. Sci. U.S.A. 100, 1238-1243. https://doi.org/10.1073/pnas.242716099
  63. Spite, M., Claria, J. and Serhan, C. N. (2014) Resolvins, specialized proresolving lipid mediators, and their potential roles in metabolic diseases. Cell Metab. 19, 21-36. https://doi.org/10.1016/j.cmet.2013.10.006
  64. Stalder, A. K., Lott, D., Strasser, D. S., Cruz, H. G., Krause, A., Groenen, P. M. and Dingemanse, J. (2017) Biomarker-guided clinical development of the first-in-class anti-inflammatory FPR2/ALX agonist ACT-389949. Br. J. Clin. Pharmacol. 83, 476-486. https://doi.org/10.1111/bcp.13149
  65. Stark, D. T. and Bazan, N. G. (2011) Neuroprotectin D1 induces neuronal survival and downregulation of amyloidogenic processing in Alzheimer's disease cellular models. Mol. Neurobiol. 43, 131-138. https://doi.org/10.1007/s12035-011-8174-4
  66. Sun, A. R., Wu, X., Liu, B., Chen, Y., Armitage, C. W., Kollipara, A., Crawford, R., Beagley, K. W., Mao, X., Xiao, Y. and Prasadam, I. (2019) Pro-resolving lipid mediator ameliorates obesity induced osteoarthritis by regulating synovial macrophage polarisation. Sci. Rep. 9, 426. https://doi.org/10.1038/s41598-018-36909-9
  67. Tang, D., Fu, G., Li, W., Sun, P., Loughran, P. A., Deng, M., Scott, M. J. and Billiar, T. R. (2021) Maresin 1 protects the liver against ischemia/reperfusion injury via the ALXR/Akt signaling pathway. Mol. Med. 27, 18.
  68. Titos, E., Rius, B., Gonzalez-Periz, A., Lopez-Vicario, C., Moran-Salvador, E., Martinez-Clemente, M., Arroyo, V. and Claria, J. (2011) Resolvin D1 and its precursor docosahexaenoic acid promote resolution of adipose tissue inflammation by eliciting macrophage polarization toward an M2-like phenotype. J. Immunol. 187, 5408-5418. https://doi.org/10.4049/jimmunol.1100225
  69. Titos, E., Rius, B., Lopez-Vicario, C., Alcaraz-Quiles, J., Garcia-Alonso, V., Lopategi, A., Dalli, J., Lozano, J.J., Arroyo, V., Delgado, S., Serhan, C. N. and Claria, J. (2016) Signaling and immunoresolving actions of resolvin D1 in inflamed human visceral adipose tissue. J. Immunol. 197, 3360-3370. https://doi.org/10.4049/jimmunol.1502522
  70. Tourki, B., Kain, V., Shaikh, S. R., Leroy, X., Serhan, C. N. and Halade, G. V. (2020) Deficit of resolution receptor magnifies inflammatory leukocyte directed cardiorenal and endothelial dysfunction with signs of cardiomyopathy of obesity. FASEB J. 34, 10560-10573. https://doi.org/10.1096/fj.202000495RR
  71. Viola, J. R., Lemnitzer, P., Jansen, Y., Csaba, G., Winter, C., Neideck, C., Silvestre-Roig, C., Dittmar, G., Doring, Y., Drechsler, M., Weber, C., Zimmer, R., Cenac, N. and Soehnlein, O. (2016) Resolving lipid mediators Maresin 1 and Resolvin D2 prevent atheroprogression in mice. Circ. Res. 119, 1030-1038. https://doi.org/10.1161/CIRCRESAHA.116.309492
  72. Zhao, Y., Calon, F., Julien, C., Winkler, J. W., Petasis, N. A., Lukiw, W. J. and Bazan, N. G. (2011) Docosahexaenoic acid-derived neuro-protectin D1 induces neuronal survival via secretase- and PPARγ-mediated mechanisms in Alzheimer's disease models. PLoS ONE 6, e15816. https://doi.org/10.1371/journal.pone.0015816
  73. Zhu, M,. Wang, X., Hjorth, E., Colas, R. A., Schroeder, L., Granholm, A. C., Serhan, C. N. and Schultzberg, M. (2016) Pro-resolving lipid mediators improve neuronal survival and increase Aβ42 phagocytosis. Mol. Neurobiol. 53, 2733-2749. https://doi.org/10.1007/s12035-015-9544-0

Cited by

  1. Monocyte to High-Density Lipoprotein Cholesterol Ratio at the Nexus of Type 2 Diabetes Mellitus Patients With Metabolic-Associated Fatty Liver Disease vol.12, 2021, https://doi.org/10.3389/fphys.2021.762242