Browse > Article
http://dx.doi.org/10.4062/biomolther.2021.094

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)
Publication Information
Biomolecules & Therapeutics / v.29, no.5, 2021 , pp. 455-464 More about this Journal
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
Specialized pro-resolving mediators; Resolvins; Maresins; NAFLDs; Adipose tissue;
Citations & Related Records
연도 인용수 순위
  • Reference
1 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.   DOI
2 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.   DOI
3 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.
4 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.   DOI
5 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.   DOI
6 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.   DOI
7 Lumeng, C. N. and Saltiel, A. R. (2011) Inflammatory links between obesity and metabolic disease. J. Clin. Invest. 121, 2111-2117.   DOI
8 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.   DOI
9 Serhan, C. N. (2017) Discovery of specialized pro-resolving mediators marks the dawn of resolution physiology and pharmacology. Mol. Aspects Med. 58, 1-11.   DOI
10 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.   DOI
11 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.   DOI
12 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.   DOI
13 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.   DOI
14 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.   DOI
15 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.   DOI
16 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.   DOI
17 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.   DOI
18 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.   DOI
19 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.   DOI
20 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.   DOI
21 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.   DOI
22 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.   DOI
23 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.   DOI
24 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.
25 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.   DOI
26 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.   DOI
27 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.   DOI
28 Koyama, Y. and Brenner, D. A. (2017) Liver inflammation and fibrosis. J. Clin. Invest. 127, 55-64.   DOI
29 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.   DOI
30 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. .
31 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.   DOI
32 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.   DOI
33 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.   DOI
34 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.   DOI
35 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.   DOI
36 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.   DOI
37 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.   DOI
38 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.   DOI
39 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.   DOI
40 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.   DOI
41 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.   DOI
42 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.
43 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.   DOI
44 Neuschwander-Tetri, B. A. (2020) Therapeutic landscape for NAFLD in 2020. Gastroenterology 158, 1984-1998.e3.   DOI
45 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.   DOI
46 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.   DOI
47 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.   DOI
48 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.   DOI
49 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.   DOI
50 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.   DOI
51 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.   DOI
52 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.   DOI
53 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.   DOI
54 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.   DOI
55 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.   DOI
56 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.   DOI
57 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.   DOI
58 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.   DOI
59 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.   DOI
60 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.   DOI
61 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.   DOI
62 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.   DOI
63 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.   DOI
64 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.   DOI
65 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.   DOI
66 Fredman, G. and Tabas, I. (2017) Boosting inflammation resolution in atherosclerosis: the next frontier for therapy. Am. J. Pathol. 187, 1211-1221.   DOI
67 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.   DOI
68 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.   DOI
69 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.   DOI
70 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.   DOI
71 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.   DOI
72 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.   DOI
73 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.   DOI