Novel action of carotenoids on non-alcoholic fatty liver disease: Macrophage polarization and liver homeostasis

Nutrients

Volumn 8, Issue 7, 2016, Pages

  Ni, Yinhua ^a   Zhuge, Fen ^a   Nagashimada, Mayumi ^a   Ota, Tsuguhito ^a  

^a KANAZAWA UNIVERSITY   (Japan)

Author keywords

Antioxidant; Astaxanthin; Carotenoids; Fibrosis; Inflammation; Insulin resistance; Macrophages Kupffer cells; NAFLD NASH; cryptoxanthin

Indexed keywords

ASTAXANTHIN; BETA CRYPTOXANTHIN; CAROTENOID; CHEMOKINE RECEPTOR CCR1; CHEMOKINE RECEPTOR CCR2; CHEMOKINE RECEPTOR CCR5; INTERFERON REGULATORY FACTOR; INTERLEUKIN 10; INTERLEUKIN 13; INTERLEUKIN 3; INTERLEUKIN 4; STAT1 PROTEIN; TRACE ELEMENT; ANTIINFLAMMATORY AGENT; ANTIOXIDANT; XANTHOPHYLL;

CYTOKINE PRODUCTION; DIETARY INTAKE; DISEASE COURSE; DOWN REGULATION; DRUG MECHANISM; HOMEOSTASIS; HUMAN; INFLAMMATION; INSULIN RESISTANCE; KUPFFER CELL; MACROPHAGE; NONALCOHOLIC FATTY LIVER; PHAGOCYTOSIS; POLARIZATION; REVIEW; SIGNAL TRANSDUCTION; UPREGULATION; ANIMAL; CELL POLARITY; DISEASE MODEL; DRUG EFFECTS; LIVER; MACROPHAGE ACTIVATION; METABOLIC SYNDROME X; METABOLISM; NON-ALCOHOLIC FATTY LIVER DISEASE; RANDOMIZED CONTROLLED TRIAL (TOPIC);

ANIMALS; ANTI-INFLAMMATORY AGENTS; ANTIOXIDANTS; BETA-CRYPTOXANTHIN; CAROTENOIDS; CELL POLARITY; DISEASE MODELS, ANIMAL; DISEASE PROGRESSION; HOMEOSTASIS; HUMANS; KUPFFER CELLS; LIVER; MACROPHAGE ACTIVATION; METABOLIC SYNDROME X; MICRONUTRIENTS; NON-ALCOHOLIC FATTY LIVER DISEASE; RANDOMIZED CONTROLLED TRIALS AS TOPIC; XANTHOPHYLLS;

EID: 85015350361     PISSN: None     EISSN: 20726643     Source Type: Journal    
DOI: 10.3390/nu8070391     Document Type: Review

References (123)

1. Pacifico, L.; Anania, C.; Martino, F.; Poggiogalle, E.; Chiarelli, F.; Arca, M.; Chiesa, C. Management of metabolic syndrome in children and adolescents. Nutr. Metab. Cardiovasc. Dis. 2011, 21, 455-466. [CrossRef] [PubMed]
2. Brunt, E.M.; Kleiner, D.E.; Wilson, L.A.; Unalp, A.; Behling, C.E.; Lavine, J.E.; Neuschwander-Tetri, B.A.; NASH Clinical Research Network. Portal chronic inflammation in nonalcoholic fatty liver disease (NAFLD): A histologic marker of advanced nafld-clinicopathologic correlations from the nonalcoholic steatohepatitis clinical research network. Hepatology 2009, 49, 809-820. [CrossRef] [PubMed]
3. Yatsuji, S.; Hashimoto, E.; Tobari, M.; Taniai, M.; Tokushige, K.; Shiratori, K. Clinical features and outcomes of cirrhosis due to non-alcoholic steatohepatitis compared with cirrhosis caused by chronic hepatitis C. J. Gastroenterol. Hepatol. 2009, 24, 248-254. [CrossRef] [PubMed]
4. Fassio, E.; Alvarez, E.; Dominguez, N.; Landeira, G.; Longo, C. Natural history of nonalcoholic steatohepatitis: A longitudinal study of repeat liver biopsies. Hepatology 2004, 40, 820-826. [CrossRef] [PubMed]
5. Ono, M.; Saibara, T. Clinical features of nonalcoholic steatohepatitis in Japan: Evidence from the literature. J. Gastroenterol. 2006, 41, 725-732. [CrossRef] [PubMed]
6. Day, C.P.; James, O.F. Steatohepatitis: A tale of two "hits"? Gastroenterology 1998, 114, 842-845. [CrossRef]
7. Ota, T.; Takamura, T.; Kurita, S.; Matsuzawa, N.; Kita, Y.; Uno, M.; Akahori, H.; Misu, H.; Sakurai, M.; Zen, Y.; et al. Insulin resistance accelerates a dietary rat model of nonalcoholic steatohepatitis. Gastroenterology 2007,132, 282-293. [CrossRef] [PubMed]
8. Takaki, A.; Kawai, D.; Yamamoto, K. Multiple hits, including oxidative stress, as pathogenesis and treatment target in non-alcoholic steatohepatitis (NASH). Int. J. Mol. Sci. 2013, 14, 20704-20728. [CrossRef] [PubMed]
9. Marchesini, G.; Brizi, M.; Bianchi, G.; Tomassetti, S.; Bugianesi, E.; Lenzi, M.; McCullough, A.J.; Natale, S.; Forlani, G.; Melchionda, N. Nonalcoholic fatty liver disease: A feature of the metabolic syndrome. Diabetes 2001, 50, 1844-1850. [CrossRef] [PubMed]
10. Hebbard, L.; George, J. Animal models of nonalcoholic fatty liver disease. Nat. Rev. Gastroenterol. Hepatol. 2011, 8, 35-44. [CrossRef] [PubMed]
11. Matsumoto, M.; Hada, N.; Sakamaki, Y.; Uno, A.; Shiga, T.; Tanaka, C.; Ito, T.; Katsume, A.; Sudoh, M. An improved mouse model that rapidly develops fibrosis in non-alcoholic steatohepatitis. Int. J. Exp. Pathol. 2013, 94, 93-103. [CrossRef] [PubMed]
12. Wada, T.; Kenmochi, H.; Miyashita, Y.; Sasaki, M.; Ojima, M.; Sasahara, M.; Koya, D.; Tsuneki, H.; Sasaoka, T. Spironolactone improves glucose and lipid metabolism by ameliorating hepatic steatosis and inflammation and suppressing enhanced gluconeogenesis induced by high-fat and high-fructose diet. Endocrinology 2010, 151, 2040-2049. [CrossRef] [PubMed]
13. Matsuzawa, N.; Takamura, T.; Kurita, S.; Misu, H.; Ota, T.; Ando, H.; Yokoyama, M.; Honda, M.; Zen, Y.; Nakanuma, Y.; et al. Lipid-induced oxidative stress causes steatohepatitis in mice fed an atherogenic diet. Hepatology 2007, 46, 1392-1403. [CrossRef] [PubMed]
14. Younossi, Z.M. Review article: Current management of non-alcoholic fatty liver disease and non-alcoholic steatohepatitis. Aliment. Pharmacol. Ther. 2008, 28, 2-12. [CrossRef] [PubMed]
15. Arab, J.P.; Candia, R.; Zapata, R.; Munoz, C.; Arancibia, J.P.; Poniachik, J.; Soza, A.; Fuster, F.; Brahm, J.; Sanhueza, E.; et al. Management of nonalcoholic fatty liver disease: An evidence-based clinical practice review. World J. Gastroenterol. 2014, 20, 12182-12201. [CrossRef] [PubMed]
16. Musso, G.; Gambino, R.; Cassader, M.; Pagano, G. A meta-analysis of randomized trials for the treatment of nonalcoholic fatty liver disease. Hepatology 2010, 52, 79-104. [CrossRef] [PubMed]
17. Sanyal, A.J.; Chalasani, N.; Kowdley, K.V.; McCullough, A.; Diehl, A.M.; Bass, N.M.; Neuschwander-Tetri, B.A.; Lavine, J.E.; Tonascia, J.; Unalp, A.; et al. Pioglitazone, vitamin E, or placebo for nonalcoholic steatohepatitis. N. Engl. J. Med. 2010, 362, 1675-1685. [CrossRef] [PubMed]
18. Lavine, J.E.; Schwimmer, J.B.; van Natta, M.L.; Molleston, J.P.; Murray, K.F.; Rosenthal, P.; Abrams, S.H.; Scheimann, A.O.; Sanyal, A.J.; Chalasani, N.; et al. Effect of vitamin E or metformin for treatment of nonalcoholic fatty liver disease in children and adolescents: The tonic randomized controlled trial. JAMA 2011, 305, 1659-1668. [CrossRef] [PubMed]
19. Odegaard, J.I.; Ricardo-Gonzalez, R.R.; Eagle, A.R.; Vats, D.; Morel, C.R.; Goforth, M.H.; Subramanian, V.; Mukundan, L.; Ferrante, A.W.; Chawla, A. Alternative M2 activation of Kupffer cells by ppardelta ameliorates obesity-induced insulin resistance. Cell Metab. 2008, 7, 496-507. [CrossRef] [PubMed]
20. Martinez, F.O.; Gordon, S. The M1 and M2 paradigm of macrophage activation: Time for reassessment. F1000prime Rep. 2014, 6, 13. [CrossRef] [PubMed]
21. Sica, A.; Mantovani, A. Macrophage plasticity and polarization: In vivo veritas. J. Clin. Investig. 2012, 122, 787-795. [CrossRef] [PubMed]
22. Wan, J.; Benkdane, M.; Teixeira-Clerc, F.; Bonnafous, S.; Louvet, A.; Lafdil, F.; Pecker, F.; Tran, A.; Gual, P.; Mallat, A.; et al. M2 Kupffer cells promote M1 Kupffer cell apoptosis: A protective mechanism against alcoholic and nonalcoholic fatty liver disease. Hepatology 2014, 59, 130-142. [CrossRef] [PubMed]
23. Xue, J.; Sharma, V.; Hsieh, M.H.; Chawla, A.; Murali, R.; Pandol, S.J.; Habtezion, A. Alternatively activated macrophages promote pancreatic fibrosis in chronic pancreatitis. Nat. Commun. 2015, 6, 7158. [CrossRef] [PubMed]
24. Rinella, M.E.; Sanyal, A.J. Management of NAFLD: A stage-based approach. Nat. Rev. Gastroenterol. Hepatol. 2016, 13, 196-205. [CrossRef] [PubMed]
25. Wong, V.W.; Chan, R.S.;Wong, G.L.; Cheung, B.H.; Chu,W.C.; Yeung, D.K.; Chim, A.M.; Lai, J.W.; Li, L.S.; Sea, M.M.; et al. Community-based lifestyle modification programme for non-alcoholic fatty liver disease: A randomized controlled trial. J. Hepatol. 2013, 59, 536-542. [CrossRef] [PubMed]
26. Promrat, K.; Kleiner, D.E.; Niemeier, H.M.; Jackvony, E.; Kearns, M.; Wands, J.R.; Fava, J.L.; Wing, R.R. Randomized controlled trial testing the effects of weight loss on nonalcoholic steatohepatitis. Hepatology 2010, 51, 121-129. [CrossRef] [PubMed]
27. Lassailly, G.; Caiazzo, R.; Buob, D.; Pigeyre, M.; Verkindt, H.; Labreuche, J.; Raverdy, V.; Leteurtre, E.; Dharancy, S.; Louvet, A.; et al. Bariatric surgery reduces features of nonalcoholic steatohepatitis in morbidly obese patients. Gastroenterology 2015, 149, 379-388. [CrossRef] [PubMed]
28. Centis, E.; Moscatiello, S.; Bugianesi, E.; Bellentani, S.; Fracanzani, A.L.; Calugi, S.; Petta, S.; Dalle Grave, R.; Marchesini, G. Stage of change and motivation to healthier lifestyle in non-alcoholic fatty liver disease. J. Hepatol. 2013, 58, 771-777. [CrossRef] [PubMed]
29. St George, A.; Bauman, A.; Johnston, A.; Farrell, G.; Chey, T.; George, J. Independent effects of physical activity in patients with nonalcoholic fatty liver disease. Hepatology 2009, 50, 68-76. [CrossRef] [PubMed]
30. Johnson, N.A.; Sachinwalla, T.; Walton, D.W.; Smith, K.; Armstrong, A.; Thompson, M.W.; George, J. Aerobic exercise training reduces hepatic and visceral lipids in obese individuals without weight loss. Hepatology 2009, 50, 1105-1112. [CrossRef] [PubMed]
31. Hallsworth, K.; Fattakhova, G.; Hollingsworth, K.G.; Thoma, C.; Moore, S.; Taylor, R.; Day, C.P.; Trenell, M.I. Resistance exercise reduces liver fat and its mediators in non-alcoholic fatty liver disease independent of weight loss. Gut 2011, 60, 1278-1283. [CrossRef] [PubMed]
32. Musso, G.; Gambino, R.; de Michieli, F.; Cassader, M.; Rizzetto, M.; Durazzo, M.; Faga, E.; Silli, B.; Pagano, G. Dietary habits and their relations to insulin resistance and postprandial lipemia in nonalcoholic steatohepatitis. Hepatology 2003, 37, 909-916. [CrossRef] [PubMed]
33. Dongiovanni, P.; Lanti, C.; Riso, P.; Valenti, L. Nutritional therapy for nonalcoholic fatty liver disease. J. Nutr. Biochem. 2016, 29, 1-11. [CrossRef] [PubMed]
34. Zhu, F.S.; Liu, S.; Chen, X.M.; Huang, Z.G.; Zhang, D.W. Effects of n-3 polyunsaturated fatty acids from seal oils on nonalcoholic fatty liver disease associated with hyperlipidemia. World J. Gastroenterol. 2008, 14, 6395-6400. [CrossRef] [PubMed]
35. Parker, H.M.; Johnson, N.A.; Burdon, C.A.; Cohn, J.S.; O'Connor, H.T.; George, J. Omega-3 supplementation and non-alcoholic fatty liver disease: A systematic review and meta-analysis. J. Hepatol. 2012, 56, 944-951. [CrossRef] [PubMed]
36. Del Ben, M.; Polimeni, L.; Baratta, F.; Pastori, D.; Angelico, F. The role of nutraceuticals for the treatment of non-alcoholic fatty liver disease. Br. J. Clin. Pharmacol. 2016. [CrossRef] [PubMed]
37. Gordon, S.; Martinez, F.O. Alternative activation of macrophages: Mechanism and functions. Immunity 2010, 32, 593-604. [CrossRef] [PubMed]
38. Sica, A.; Invernizzi, P.; Mantovani, A. Macrophage plasticity and polarization in liver homeostasis and pathology. Hepatology 2014, 59, 2034-2042. [CrossRef] [PubMed]
39. Crispe, I.N. Hepatic t cells and liver tolerance. Nat. Rev. Immunol. 2003, 3, 51-62. [CrossRef] [PubMed]
40. Vonghia, L.; Michielsen, P.; Francque, S. Immunological mechanisms in the pathophysiology of non-alcoholic steatohepatitis. Int. J. Mol. Sci. 2013, 14, 19867-19890. [CrossRef] [PubMed]
41. Duffield, J.S.; Forbes, S.J.; Constandinou, C.M.; Clay, S.; Partolina, M.; Vuthoori, S.; Wu, S.; Lang, R.; Iredale, J.P. Selective depletion of macrophages reveals distinct, opposing roles during liver injury and repair. J. Clin. Investig. 2005, 115, 56-65. [PubMed]
42. Liaskou, E.; Zimmermann, H.W.; Li, K.K.; Oo, Y.H.; Suresh, S.; Stamataki, Z.; Qureshi, O.; Lalor, P.F.; Shaw, J.; Syn, W.K.; et al. Monocyte subsets in human liver disease show distinct phenotypic and functional characteristics. Hepatology 2013, 57, 385-398. [PubMed]
43. Jager, J.; Aparicio-Vergara, M.; Aouadi, M. Liver innate immune cells and insulin resistance: The multiple facets of Kupffer cells. J. Intern. Med. 2016. [CrossRef] [PubMed]
44. Ikarashi, M.; Nakashima, H.; Kinoshita, M.; Sato, A.; Nakashima, M.; Miyazaki, H.; Nishiyama, K.; Yamamoto, J.; Seki, S. Distinct development and functions of resident and recruited liver Kupffer cells/macrophages. J. Leukoc. Biol. 2013, 94, 1325-1336. [PubMed]
45. Klein, I.; Cornejo, J.C.; Polakos, N.K.; John, B.;Wuensch, S.A.; Topham, D.J.; Pierce, R.H.; Crispe, I.N. Kupffer cell heterogeneity: Functional properties of bone marrow derived and sessile hepatic macrophages. Blood 2007, 110, 4077-4085. [PubMed]
46. Biswas, S.K.; Mantovani, A. Macrophage plasticity and interaction with lymphocyte subsets: Cancer as a paradigm. Nat. Immunol. 2010, 11, 889-896. [PubMed]
47. Zhang, Y.; Zhang, M.; Zhong, M.; Suo, Q.; Lv, K. Expression profiles of mirnas in polarized macrophages. Int. J. Mol. Med. 2013, 31, 797-802. [PubMed]
48. Sica, A.; Bronte, V. Altered macrophage differentiation and immune dysfunction in tumor development. J. Clin. Investig. 2007, 117, 1155-1166. [CrossRef] [PubMed]
49. Krausgruber, T.; Blazek, K.; Smallie, T.; Alzabin, S.; Lockstone, H.; Sahgal, N.; Hussell, T.; Feldmann, M.; Udalova, I.A. IRF5 promotes inflammatory macrophage polarization and TH1-TH17 responses. Nat. Immunol. 2011, 12, 231-238. [PubMed]
50. Pauleau, A.L.; Rutschman, R.; Lang, R.; Pernis, A.; Watowich, S.S.; Murray, P.J. Enhancer-mediated control of macrophage-specific arginase I expression. J. Immunol. 2004, 172, 7565-7573. [PubMed]
51. Lang, R.; Patel, D.; Morris, J.J.; Rutschman, R.L.; Murray, P.J. Shaping gene expression in activated and resting primary macrophages by IL-10. J. Immunol. 2002, 169, 2253-2263. [CrossRef] [PubMed]
52. Gordon, S. Alternative activation of macrophages. Nat. Rev. Immunol. 2003, 3, 23-35. [CrossRef] [PubMed]
53. Xu, H.; Zhu, J.; Smith, S.; Foldi, J.; Zhao, B.; Chung, A.Y.; Outtz, H.; Kitajewski, J.; Shi, C.; Weber, S.; et al. Notch-RBP-J signaling regulates the transcription factor IRF8 to promote inflammatory macrophage polarization. Nat. Immunol. 2012, 13, 642-650. [CrossRef] [PubMed]
54. Whyte, C.S.; Bishop, E.T.; Ruckerl, D.; Gaspar-Pereira, S.; Barker, R.N.; Allen, J.E.; Rees, A.J.;Wilson, H.M. Suppressor of cytokine signaling (SOCS)1 is a key determinant of differential macrophage activation and function. J. Leukoc. Biol. 2011, 90, 845-854. [CrossRef] [PubMed]
55. Liu, Y.; Stewart, K.N.; Bishop, E.; Marek, C.J.; Kluth, D.C.; Rees, A.J.; Wilson, H.M. Unique expression of suppressor of cytokine signaling 3 is essential for classical macrophage activation in rodents in vitro andin vivo. J. Immunol. 2008, 180, 6270-6278. [CrossRef] [PubMed]
56. Wang, Y.C.; He, F.; Feng, F.; Liu, X.W.; Dong, G.Y.; Qin, H.Y.; Hu, X.B.; Zheng, M.H.; Liang, L.; Feng, L.; et al. Notch signaling determines the M1 versus M2 polarization of macrophages in antitumor immune responses. Cancer Res. 2010, 70, 4840-4849. [CrossRef] [PubMed]
57. Odegaard, J.I.; Ricardo-Gonzalez, R.R.; Goforth, M.H.; Morel, C.R.; Subramanian, V.; Mukundan, L.; Eagle, A.R.; Vats, D.; Brombacher, F.; Ferrante, A.W.; et al. Macrophage-specific ppargamma controls alternative activation and improves insulin resistance. Nature 2007, 447, 1116-1120. [CrossRef] [PubMed]
58. Kang, K.; Reilly, S.M.; Karabacak, V.; Gangl, M.R.; Fitzgerald, K.; Hatano, B.; Lee, C.H. Adipocyte-derived TH2 cytokines and myeloid ppardelta regulate macrophage polarization and insulin sensitivity. Cell Metab. 2008, 7, 485-495. [CrossRef] [PubMed]
59. Liao, X.; Sharma, N.; Kapadia, F.; Zhou, G.; Lu, Y.; Hong, H.; Paruchuri, K.; Mahabeleshwar, G.H.; Dalmas, E.; Venteclef, N.; et al. Kruppel-like factor 4 regulates macrophage polarization. J. Clin. Investig. 2011, 121, 2736-2749. [CrossRef] [PubMed]
60. Mahabeleshwar, G.H.; Kawanami, D.; Sharma, N.; Takami, Y.; Zhou, G.; Shi, H.; Nayak, L.; Jeyaraj, D.; Grealy, R.; White, M.; et al. The myeloid transcription factor KLF2 regulates the host response to polymicrobial infection and endotoxic shock. Immunity 2011, 34, 715-728. [CrossRef] [PubMed]
61. Pello, O.M.; De Pizzol, M.; Mirolo, M.; Soucek, L.; Zammataro, L.; Amabile, A.; Doni, A.; Nebuloni, M.; Swigart, L.B.; Evan, G.I.; et al. Role of c-MYC in alternative activation of human macrophages and tumor-associated macrophage biology. Blood 2012, 119, 411-421. [CrossRef] [PubMed]
62. Hagemann, T.; Lawrence, T.; McNeish, I.; Charles, K.A.; Kulbe, H.; Thompson, R.G.; Robinson, S.C.; Balkwill, F.R. "Re-educating" tumor-associated macrophages by targeting nf-kappab. J. Exp. Med. 2008, 205, 1261-1268. [CrossRef] [PubMed]
63. Han, M.S.; Jung, D.Y.; Morel, C.; Lakhani, S.A.; Kim, J.K.; Flavell, R.A.; Davis, R.J. JNK expression by macrophages promotes obesity-induced insulin resistance and inflammation. Science 2013, 339, 218-222. [CrossRef] [PubMed]
64. Takeda, N.; O'Dea, E.L.; Doedens, A.; Kim, J.W.;Weidemann, A.; Stockmann, C.; Asagiri, M.; Simon, M.C.; Hoffmann, A.; Johnson, R.S. Differential activation and antagonistic function of hif-α isoforms in macrophages are essential for NO homeostasis. Genes Dev. 2010, 24, 491-501. [CrossRef] [PubMed]
65. Wu, X.Q.; Dai, Y.; Yang, Y.; Huang, C.; Meng, X.M.;Wu, B.M.; Li, J. Emerging role of microRNAs in regulating macrophage activation and polarization in immune response and inflammation. Immunology 2016, 148, 237-248. [CrossRef] [PubMed]
66. Graff, J.W.; Dickson, A.M.; Clay, G.; McCaffrey, A.P.; Wilson, M.E. Identifying functional micrornas in macrophages with polarized phenotypes. J. Biol. Chem. 2012, 287, 21816-21825. [CrossRef] [PubMed]
67. Bilzer, M.; Roggel, F.; Gerbes, A.L. Role of Kupffer cells in host defense and liver disease. Liver Int. 2006, 26, 1175-1186. [CrossRef] [PubMed]
68. Swirski, F.K.; Libby, P.; Aikawa, E.; Alcaide, P.; Luscinskas, F.W.;Weissleder, R.; Pittet, M.J. Ly-6Chi monocytes dominate hypercholesterolemia-associated monocytosis and give rise to macrophages in atheromata. J. Clin. Investig. 2007, 117, 195-205. [CrossRef] [PubMed]
69. Odegaard, J.I.; Chawla, A. Alternative macrophage activation and metabolism. Ann. Rev. Pathol. 2011, 6, 275-297. [CrossRef] [PubMed]
70. Duarte, N.; Coelho, I.C.; Patarrao, R.S.; Almeida, J.I.; Penha-Goncalves, C.; Macedo, M.P. How inflammation impinges on NAFLD: A role for Kupffer cells. BioMed Res. Int. 2015, 2015, 984578. [CrossRef] [PubMed]
71. Petrasek, J.; Bala, S.; Csak, T.; Lippai, D.; Kodys, K.; Menashy, V.; Barrieau, M.; Min, S.Y.; Kurt-Jones, E.A.; Szabo, G. IL-1 receptor antagonist ameliorates inflammasome-dependent alcoholic steatohepatitis in mice. J. Clin. Investig. 2012, 122, 3476-3489. [CrossRef] [PubMed]
72. Tomiyama, K.; Ikeda, A.; Ueki, S.; Nakao, A.; Stolz, D.B.; Koike, Y.; Afrazi, A.; Gandhi, C.; Tokita, D.; Geller, D.A.; et al. Inhibition of Kupffer cell-mediated early proinflammatory response with carbon monoxide in transplant-induced hepatic ischemia/reperfusion injury in rats. Hepatology 2008, 48, 1608-1620. [CrossRef] [PubMed]
73. Liaskou, E.;Wilson, D.V.; Oo, Y.H. Innate immune cells in liver inflammation. Mediat. Inflamm. 2012, 2012, 949157. [CrossRef] [PubMed]
74. Tanti, J.F.; Jager, J. Cellular mechanisms of insulin resistance: Role of stress-regulated serine kinases and insulin receptor substrates (IRS) serine phosphorylation. Curr. Opin. Pharmacol. 2009, 9, 753-762. [CrossRef] [PubMed]
75. Senn, J.J.; Klover, P.J.; Nowak, I.A.; Mooney, R.A. Interleukin-6 induces cellular insulin resistance in hepatocytes. Diabetes 2002, 51, 3391-3399. [CrossRef] [PubMed]
76. Olefsky, J.M.; Glass, C.K. Macrophages, inflammation, and insulin resistance. Ann. Rev. Physiol. 2010, 72, 219-246. [CrossRef] [PubMed]
77. Wick, G.; Grundtman, C.; Mayerl, C.;Wimpissinger, T.F.; Feichtinger, J.; Zelger, B.; Sgonc, R.;Wolfram, D. The immunology of fibrosis. Ann. Rev. Immunol. 2013, 31, 107-135. [CrossRef] [PubMed]
78. Schuppan, D.; Kim, Y.O. Evolving therapies for liver fibrosis. J. Clin. Investig. 2013, 123, 1887-1901. [CrossRef] [PubMed]
79. Wynn, T.A.; Barron, L. Macrophages: Master regulators of inflammation and fibrosis. Semin. Liver Dis. 2010, 30, 245-257. [CrossRef] [PubMed]
80. Takehara, T.; Tatsumi, T.; Suzuki, T.; Rucker, E.B., III; Hennighausen, L.; Jinushi, M.; Miyagi, T.; Kanazawa, Y.; Hayashi, N. Hepatocyte-specific disruption of BCL-XL leads to continuous hepatocyte apoptosis and liver fibrotic responses. Gastroenterology 2004, 127, 1189-1197. [CrossRef] [PubMed]
81. Otogawa, K.; Kinoshita, K.; Fujii, H.; Sakabe, M.; Shiga, R.; Nakatani, K.; Ikeda, K.; Nakajima, Y.; Ikura, Y.; Ueda, M.; et al. Erythrophagocytosis by liver macrophages (Kupffer cells) promotes oxidative stress, inflammation, and fibrosis in a rabbit model of steatohepatitis: Implications for the pathogenesis of human nonalcoholic steatohepatitis. Am. J. Pathol. 2007, 170, 967-980. [CrossRef] [PubMed]
82. Patsenker, E.; Popov, Y.; Stickel, F.; Jonczyk, A.; Goodman, S.L.; Schuppan, D. Inhibition of integrin alphavbeta6 on cholangiocytes blocks transforming growth factor-beta activation and retards biliary fibrosis progression. Gastroenterology 2008, 135, 660-670. [CrossRef] [PubMed]
83. 1. J. Exp. Med. 2001, 194, 809-821. [CrossRef] [PubMed]
84. Karlmark, K.R.; Weiskirchen, R.; Zimmermann, H.W.; Gassler, N.; Ginhoux, F.; Weber, C.; Merad, M.; Luedde, T.; Trautwein, C.; Tacke, F. Hepatic recruitment of the inflammatory GR1+ monocyte subset upon liver injury promotes hepatic fibrosis. Hepatology 2009, 50, 261-274. [CrossRef] [PubMed]
85. Seki, E.; de Minicis, S.; Inokuchi, S.; Taura, K.; Miyai, K.; van Rooijen, N.; Schwabe, R.F.; Brenner, D.A. CCR2 promotes hepatic fibrosis in mice. Hepatology 2009, 50, 185-197. [CrossRef] [PubMed]
86. Stanner, S.A.; Hughes, J.; Kelly, C.N.; Buttriss, J. A review of the epidemiological evidence for the 'antioxidant hypothesis'. Public Health Nutr. 2004, 7, 407-422. [CrossRef] [PubMed]
87. Sugiura, M.; Ogawa, K.; Yano, M. Comparison of bioavailability between beta-cryptoxanthin and beta-carotene and tissue distribution in its intact form in rats. Biosci. Biotechnol. Biochem. 2014, 78, 307-310. [CrossRef] [PubMed]
88. Yilmaz, B.; Sahin, K.; Bilen, H.; Bahcecioglu, I.H.; Bilir, B.; Ashraf, S.; Halazun, K.J.; Kucuk, O. Carotenoids and non-alcoholic fatty liver disease. Hepatobiliary Surg. Nutr. 2015, 4, 161-171. [PubMed]
89. Yadav, D.; Hertan, H.I.; Schweitzer, P.; Norkus, E.P.; Pitchumoni, C.S. Serum and liver micronutrient antioxidants and serum oxidative stress in patients with chronic hepatitis C. Am. J. Gastroenterol. 2002, 97, 2634-2639. [CrossRef] [PubMed]
90. Ruhl, C.E.; Everhart, J.E. Relation of elevated serum alanine aminotransferase activity with iron and antioxidant levels in the United States. Gastroenterology 2003, 124, 1821-1829. [CrossRef]
91. Gunanti, I.R.; Marks, G.C.; Al-Mamun, A.; Long, K.Z. Low serum concentrations of carotenoids and vitamin e are associated with high adiposity in Mexican-American children. J. Nutr. 2014, 144, 489-495. [CrossRef] [PubMed]
92. Garcia, O.P.; Long, K.Z.; Rosado, J.L. Impact of micronutrient deficiencies on obesity. Nutr. Rev. 2009, 67, 559-572. [CrossRef] [PubMed]
93. Neuhouser, M.L.; Rock, C.L.; Eldridge, A.L.; Kristal, A.R.; Patterson, R.E.; Cooper, D.A.; Neumark-Sztainer, D.; Cheskin, L.J.; Thornquist, M.D. Serum concentrations of retinol, alpha-tocopherol and the carotenoids are influenced by diet, race and obesity in a sample of healthy adolescents. J. Nutr. 2001, 131, 2184-2191. [PubMed]
94. Cao, Y.; Wang, C.; Liu, J.; Liu, Z.M.; Ling, W.H.; Chen, Y.M. Greater serum carotenoid levels associated with lower prevalence of nonalcoholic fatty liver disease in Chinese adults. Sci. Rep. 2015, 5, 12951. [CrossRef] [PubMed]
95. Sugiura, M.; Nakamura, M.; Ogawa, K.; Ikoma, Y.; Yano, M. High serum carotenoids are associated with lower risk for developing elevated serum alanine aminotransferase among Japanese subjects: The mikkabi cohort study. Br. J. Nutr. 2016, 115, 1462-1469. [CrossRef] [PubMed]
96. Al-Busafi, S.A.; Bhat, M.; Wong, P.; Ghali, P.; Deschenes, M. Antioxidant therapy in nonalcoholic steatohepatitis. Hepat. Res. Treat. 2012, 2012, 947575. [CrossRef] [PubMed]
97. Chung, M.Y.; Yeung, S.F.; Park, H.J.; Volek, J.S.; Bruno, R.S. Dietary alpha-and gamma-tocopherol supplementation attenuates lipopolysaccharide-induced oxidative stress and inflammatory-related responses in an obese mouse model of nonalcoholic steatohepatitis. J. Nutr. Biochem. 2010, 21, 1200-1206. [CrossRef] [PubMed]
98. Nan, Y.M.; Wu, W.J.; Fu, N.; Liang, B.L.; Wang, R.Q.; Li, L.X.; Zhao, S.X.; Zhao, J.M.; Yu, J. Antioxidants vitamin E and 1-aminobenzotriazole prevent experimental non-alcoholic steatohepatitis in mice. Scand. J. Gastroenterol. 2009, 44, 1121-1131. [CrossRef] [PubMed]
99. Rock, C.L.; Jacob, R.A.; Bowen, P.E. Update on the biological characteristics of the antioxidant micronutrients: vitamin C, vitamin E, and the carotenoids. J. Am. Diet. Assoc. 1996, 96, 693-702. [CrossRef]
100. Kaulmann, A.; Bohn, T. Carotenoids, inflammation, and oxidative stress-Implications of cellular signaling pathways and relation to chronic disease prevention. Nutr. Res. 2014, 34, 907-929. [CrossRef] [PubMed]
101. Ni, Y.; Nagashimada, M.; Zhan, L.; Nagata, N.; Kobori, M.; Sugiura, M.; Ogawa, K.; Kaneko, S.; Ota, T. Prevention and reversal of lipotoxicity-induced hepatic insulin resistance and steatohepatitis in mice by an antioxidant carotenoid, beta-cryptoxanthin. Endocrinology 2015, 156, 987-999. [CrossRef] [PubMed]
102. Ni, Y.; Nagashimada, M.; Zhuge, F.; Zhan, L.; Nagata, N.; Tsutsui, A.; Nakanuma, Y.; Kaneko, S.; Ota, T. Astaxanthin prevents and reverses diet-induced insulin resistance and steatohepatitis in mice: A comparison with vitamin E. Sci. Rep. 2015, 5, 17192. [CrossRef] [PubMed]
103. Sugiura, M.; Nakamura, M.; Ogawa, K.; Ikoma, Y.; Matsumoto, H.; Ando, F.; Shimokata, H.; Yano, M. Synergistic interaction of cigarette smoking and alcohol drinking with serum carotenoid concentrations: Findings from a middle-aged Japanese population. Br. J. Nutr. 2009, 102, 1211-1219. [CrossRef] [PubMed]
104. Sugiura, M.; Nakamura, M.; Ikoma, Y.; Yano, M.; Ogawa, K.; Matsumoto, H.; Kato, M.; Ohshima, M.; Nagao, A. The homeostasis model assessment-insulin resistance index is inversely associated with serum carotenoids in non-diabetic subjects. J. Epidemiol. Jpn. Epidemiol. Assoc. 2006, 16, 71-78. [CrossRef]
105. Sugiura, M.; Nakamura, M.; Ikoma, Y.; Yano, M.; Ogawa, K.; Matsumoto, H.; Kato, M.; Ohshima, M.; Nagao, A. High serum carotenoids are inversely associated with serum gamma-glutamyltransferase in alcohol drinkers within normal liver function. J. Epidemiol. Jpn. Epidemiol. Assoc. 2005, 15, 180-186. [CrossRef]
106. Lorenzo, Y.; Azqueta, A.; Luna, L.; Bonilla, F.; Dominguez, G.; Collins, A.R. The carotenoid beta-cryptoxanthin stimulates the repair of DNA oxidation damage in addition to acting as an antioxidant in human cells. Carcinogenesis 2009, 30, 308-314. [CrossRef] [PubMed]
107. Unno, K.; Sugiura, M.; Ogawa, K.; Takabayashi, F.; Toda, M.; Sakuma, M.; Maeda, K.; Fujitani, K.; Miyazaki, H.; Yamamoto, H.; et al. Beta-cryptoxanthin, plentiful in Japanese mandarin orange, prevents age-related cognitive dysfunction and oxidative damage in senescence-accelerated mouse brain. Biol. Pharm. Bull. 2011, 34, 311-317. [CrossRef] [PubMed]
108. Haegele, A.D.; Gillette, C.; O'Neill, C.; Wolfe, P.; Heimendinger, J.; Sedlacek, S.; Thompson, H.J. Plasma xanthophyll carotenoids correlate inversely with indices of oxidative DNA damage and lipid peroxidation. Cancer Epidemiol. Biomark. Prev. 2000, 9, 421-425.
109. Matsumoto, C.; Ashida, N.; Yokoyama, S.; Tominari, T.; Hirata, M.; Ogawa, K.; Sugiura, M.; Yano, M.; Inada, M.; Miyaura, C. The protective effects of beta-cryptoxanthin on inflammatory bone resorption in a mouse experimental model of periodontitis. Biosci. Biotechnol. Biochem. 2013, 77, 860-862. [CrossRef] [PubMed]
110. Katsuura, S.; Imamura, T.; Bando, N.; Yamanishi, R. Beta-carotene and beta-cryptoxanthin but not lutein evoke redox and immune changes in raw264 murine macrophages. Mol. Nutr. Food Res. 2009, 53, 1396-1405. [CrossRef] [PubMed]
111. Kobori, M.; Ni, Y.; Takahashi, Y.; Watanabe, N.; Sugiura, M.; Ogawa, K.; Nagashimada, M.; Kaneko, S.; Naito, S.; Ota, T. Beta-cryptoxanthin alleviates diet-induced nonalcoholic steatohepatitis by suppressing inflammatory gene expression in mice. PLoS ONE 2014, 9, e98294. [CrossRef] [PubMed]
112. Ambati, R.R.; Phang, S.M.; Ravi, S.; Aswathanarayana, R.G. Astaxanthin: Sources, extraction, stability, biological activities and its commercial applications-A review. Mar. Drugs 2014, 12, 128-152. [CrossRef] [PubMed]
113. Guerin, M.; Huntley, M.E.; Olaizola, M. Haematococcus astaxanthin: Applications for human health and nutrition. Trends Biotechnol. 2003, 21, 210-216. [CrossRef]
114. Yuan, J.P.; Peng, J.; Yin, K.; Wang, J.H. Potential health-promoting effects of astaxanthin: A high-value carotenoid mostly from microalgae. Mol. Nutr. Food Res. 2011, 55, 150-165. [CrossRef] [PubMed]
115. Kang, J.O.; Kim, S.J.; Kim, H. Effect of astaxanthin on the hepatotoxicity, lipid peroxidation and antioxidative enzymes in the liver of CCL4-treated rats. Methods Find. Exp. Clin. Pharmacol. 2001, 23, 79-84. [CrossRef] [PubMed]
116. Jornayvaz, F.R.; Jurczak, M.J.; Lee, H.Y.; Birkenfeld, A.L.; Frederick, D.W.; Zhang, D.; Zhang, X.M.; Samuel, V.T.; Shulman, G.I. A high-fat, ketogenic diet causes hepatic insulin resistance in mice, despite increasing energy expenditure and preventing weight gain. Am. J. Physiol. Endocrinol. Metab. 2010, 299, E808-E815. [CrossRef] [PubMed]
117. Ikeuchi, M.; Koyama, T.; Takahashi, J.; Yazawa, K. Effects of astaxanthin in obese mice fed a high-fat diet. Biosci. Biotechnol. Biochem. 2007, 71, 893-899. [CrossRef] [PubMed]
118. Yang, Y.; Kim, B.; Park, Y.K.; Koo, S.I.; Lee, J.Y. Astaxanthin prevents TGFbeta1-induced pro-fibrogenic gene expression by inhibiting Smad3 activation in hepatic stellate cells. Biochim. Biophys. Acta 2015, 1850, 178-185. [CrossRef] [PubMed]
119. Yang, Y.; Bae, M.; Kim, B.; Park, Y.K.; Koo, S.I.; Lee, J.Y. Astaxanthin prevents and reverses the activation of mouse primary hepatic stellate cells. J. Nutr. Biochem. 2016, 29, 21-26. [CrossRef] [PubMed]
120. Ishiki, M.; Nishida, Y.; Ishibashi, H.;Wada, T.; Fujisaka, S.; Takikawa, A.; Urakaze, M.; Sasaoka, T.; Usui, I.; Tobe, K. Impact of divergent effects of astaxanthin on insulin signaling in l6 cells. Endocrinology 2013, 154, 2600-2612. [CrossRef] [PubMed]
121. Wang, Y.; Ausman, L.M.; Greenberg, A.S.; Russell, R.M.;Wang, X.D. Dietary lycopene and tomato extract supplementations inhibit nonalcoholic steatohepatitis-promoted hepatocarcinogenesis in rats. Int. J. Cancer 2010, 126, 1788-1796. [CrossRef] [PubMed]
122. Bahcecioglu, I.H.; Kuzu, N.; Metin, K.; Ozercan, I.H.; Ustundag, B.; Sahin, K.; Kucuk, O. Lycopene prevents development of steatohepatitis in experimental nonalcoholic steatohepatitis model induced by high-fat diet. Vet. Med. Int. 2010, 2010. [CrossRef] [PubMed]
123. Erhardt, A.; Stahl, W.; Sies, H.; Lirussi, F.; Donner, A.; Haussinger, D. Plasma levels of vitamin e and carotenoids are decreased in patients with nonalcoholic steatohepatitis (NASH). Eur. J. Med. Res. 2011, 16, 76-78. [CrossRef] [PubMed]