Younossi Z, Tacke F, Arrese M, Chander Sharma B, Mostafa I, Bugianesi E, et al. Global perspectives on nonalcoholic fatty liver disease and nonalcoholic steatohepatitis. Hepatology. 2019;69:2672–82.
Riazi K, Azhari H, Charette JH, Underwood FE, King JA, Afshar EE, et al. The prevalence and incidence of NAFLD worldwide: a systematic review and meta-analysis. Lancet Gastroenterol Hepatol. 2022;7:851–61.
Chalasani N, Younossi Z, Lavine JE, Charlton M, Cusi K, Rinella M, et al. The diagnosis and management of nonalcoholic fatty liver disease: practice guidance from the American Association for the Study of Liver Diseases. Hepatology. 2018;67:328–57.
Ishii T, Itoh K, Takahashi S, Sato H, Yanagawa T, Katoh Y, et al. Transcription factor Nrf2 coordinately regulates a group of oxidative stress-inducible genes in macrophages. J Biol Chem. 2000;275:16023–9.
Article CAS PubMed Google Scholar
Yamamoto M, Kensler TW, Motohashi H. The KEAP1-NRF2 system: a thiol-based sensor-effector apparatus for maintaining redox homeostasis. Physiol Rev. 2018;98:1169–203.
Article CAS PubMed PubMed Central Google Scholar
Chartoumpekis DV, Kensler TW. New player on an old field; the keap1/Nrf2 pathway as a target for treatment of type 2 diabetes and metabolic syndrome. Curr Diabetes Rev. 2013;9:137–45.
PubMed PubMed Central Google Scholar
Uruno A, Furusawa Y, Yagishita Y, Fukutomi T, Muramatsu H, Negishi T, et al. The Keap1-Nrf2 system prevents onset of diabetes mellitus. Mol Cell Biol. 2013;33:2996–3010.
Article CAS PubMed PubMed Central Google Scholar
Saha PK, Reddy VT, Konopleva M, Andreeff M, Chan L. The triterpenoid 2-cyano-3,12-dioxooleana-1,9-dien-28-oic-acid methyl ester has potent anti-diabetic effects in diet-induced diabetic mice and Lepr(db/db) mice. J Biol Chem. 2010;285:40581–92.
Article CAS PubMed PubMed Central Google Scholar
Yu Z, Shao W, Chiang Y, Foltz W, Zhang Z, Ling W, et al. Oltipraz upregulates the nuclear factor (erythroid-derived 2)-like 2 [corrected](NRF2) antioxidant system and prevents insulin resistance and obesity induced by a high-fat diet in C57BL/6J mice. Diabetologia. 2011;54:922–34.
Article CAS PubMed Google Scholar
de Zeeuw D, Akizawa T, Audhya P, Bakris GL, Chin M, Christ-Schmidt H, et al. Bardoxolone methyl in type 2 diabetes and stage 4 chronic kidney disease. N Engl J Med. 2013;369:2492–503.
Article PubMed PubMed Central Google Scholar
Kelley MJ, Glaser EM, Herndon JE, Becker F, Bhagat R, Zhang Y-J, et al. Safety and efficacy of weekly oral oltipraz in chronic smokers. Cancer Epidemiol Biomark Prev. 2005;14:892–9.
Fahey JW, Talalay P. Antioxidant functions of sulforaphane: a potent inducer of Phase II detoxication enzymes. Food Chem Toxicol. 1999;37:973–9.
Article CAS PubMed Google Scholar
Kobayashi EH, Suzuki T, Funayama R, Nagashima T, Hayashi M, Sekine H, et al. Nrf2 suppresses macrophage inflammatory response by blocking proinflammatory cytokine transcription. Nat Commun. 2016;7:11624. https://doi.org/10.1038/ncomms11624.
Article CAS PubMed PubMed Central Google Scholar
Houghton CA, Fassett RG, Coombes JS. Sulforaphane: translational research from laboratory bench to clinic. Nutr Rev. 2013;71:709–26.
Axelsson AS, Tubbs E, Mecham B, Chacko S, Nenonen HA, Tang Y, et al. Sulforaphane reduces hepatic glucose production and improves glucose control in patients with type 2 diabetes. Sci Transl Med. 2017;9:eaah4477. https://doi.org/10.1126/scitranslmed.aah4477.
Article CAS PubMed Google Scholar
Nagata N, Xu L, Kohno S, Ushida Y, Aoki Y, Umeda R, et al. Glucoraphanin ameliorates obesity and insulin resistance through adipose tissue browning and reduction of metabolic endotoxemia in mice. Diabetes. 2017;66:1222–36.
Article CAS PubMed Google Scholar
Kensler TW, Ng D, Carmella SG, Chen M, Jacobson LP, Muñoz A, et al. Modulation of the metabolism of airborne pollutants by glucoraphanin-rich and sulforaphane-rich broccoli sprout beverages in Qidong, China. Carcinogenesis. 2012;33:101–7.
Article CAS PubMed Google Scholar
Kitade H, Sawamoto K, Nagashimada M, Inoue H, Yamamoto Y, Sai Y, et al. CCR5 plays a critical role in obesity-induced adipose tissue inflammation and insulin resistance by regulating both macrophage recruitment and M1/M2 status. Diabetes. 2012;61:1680–90.
Article CAS PubMed PubMed Central Google Scholar
Obstfeld AE, Sugaru E, Thearle M, Francisco A-M, Gayet C, Ginsberg HN, et al. C–C chemokine receptor 2 (CCR2) regulates the hepatic recruitment of myeloid cells that promote obesity-induced hepatic steatosis. Diabetes. 2010;59:916–25.
Article CAS PubMed PubMed Central Google Scholar
Tacke F. Targeting hepatic macrophages to treat liver diseases. J Hepatol. 2017;66:1300–12.
Article CAS PubMed Google Scholar
Van den Bossche J, Baardman J, Otto NA, van der Velden S, Neele AE, van den Berg SM, et al. Mitochondrial dysfunction prevents repolarization of inflammatory macrophages. Cell Rep. 2016;17:684–96.
Cusi K. Role of obesity and lipotoxicity in the development of nonalcoholic steatohepatitis: pathophysiology and clinical implications. Gastroenterology. 2012;142:711–25.
Article CAS PubMed Google Scholar
Lin T-Y, Cantley LC, DeNicola GM, Lin T-Y, Cantley LC, DeNicola GM. NRF2 rewires cellular metabolism to support the antioxidant response. IntechOpen. 2016. https://doi.org/10.5772/65141.
Hardie DG, Ross FA, Hawley SA. AMPK: a nutrient and energy sensor that maintains energy homeostasis. Nat Rev Mol Cell Biol. 2012;13:251–62.
Article CAS PubMed PubMed Central Google Scholar
Czaja MJ. JNK regulation of hepatic manifestations of the metabolic syndrome. Trends Endocrinol Metab. 2010;21:707–13.
Article CAS PubMed PubMed Central Google Scholar
Arrese M, Cabrera D, Kalergis AM, Feldstein AE. Innate immunity and inflammation in NAFLD/NASH. Dig Dis Sci. 2016;61:1294–303.
Article CAS PubMed PubMed Central Google Scholar
Ma KL, Ruan XZ, Powis SH, Chen Y, Moorhead JF, Varghese Z. Inflammatory stress exacerbates lipid accumulation in hepatic cells and fatty livers of apolipoprotein E knockout mice. Hepatology. 2008;48:770–81.
Article CAS PubMed Google Scholar
Singh R, Wang Y, Xiang Y, Tanaka KE, Gaarde WA, Czaja MJ. Differential effects of JNK1 and JNK2 inhibition on murine steatohepatitis and insulin resistance. Hepatology. 2009;49:87–96.
Article CAS PubMed Google Scholar
Miura K, Yang L, van Rooijen N, Ohnishi H, Seki E. Hepatic recruitment of macrophages promotes nonalcoholic steatohepatitis through CCR2. Am J Physiol Gastrointest Liver Physiol. 2012;302:G1310-1321.
Article CAS PubMed PubMed Central Google Scholar
Baeck C, Wehr A, Karlmark KR, Heymann F, Vucur M, Gassler N, et al. Pharmacological inhibition of the chemokine CCL2 (MCP-1) diminishes liver macrophage infiltration and steatohepatitis in chronic hepatic injury. Gut. 2012;61:416–26.
Article CAS PubMed Google Scholar
Patsouris D, Li P-P, Thapar D, Chapman J, Olefsky JM, Neels JG. Ablation of CD11c-positive cells normalizes insulin sensitivity in obese insulin resistant animals. Cell Metab. 2008;8:301–9.
Article CAS PubMed PubMed Central Google Scholar
Odegaard JI, Ricardo-Gonzalez RR, Red Eagle A, Vats D, Morel CR, Goforth MH, et al. Alternative M2 activation of Kupffer cells by PPARdelta ameliorates obesity-induced insulin resistance. Cell Metab. 2008;7:496–507.
Article CAS PubMed PubMed Central Google Scholar
Pal S, Konkimalla VB. Sulforaphane regulates phenotypic and functional switching of both induced and spontaneously differentiating human monocytes. Int Immunopharmacol. 2016;35:85–98.
Article CAS PubMed Google Scholar
Hayes JD, Dinkova-Kostova AT. The Nrf2 regulatory network provides an interface between redox and intermediary metabolism. Trends Biochem Sci. 2014;39:199–218.
Article CAS PubMed Google Scholar
Lu SC. Glutathione synthesis. Biochim Biophys Acta. 1830;2013:3143–53.
Gowans GJ, Hawley SA, Ross FA, Hardie DG. AMP is a true physiological regulator of AMP-activated protein kinase by both allosteric activation and enhancing net phosphorylation. Cell Metab. 2013;18:556–66.
Comments (0)