Skip to main content
Hauptrubriken
CME Facharzt-Training Webinare Zeitschriften Bücher e.Medpedia Podcast
Service
Jobbörse Info & Hilfe
Fachgebiete
Anästhesiologie Allgemeinmedizin Arbeitsmedizin Augenheilkunde Chirurgie Dermatologie Gynäkologie und Geburtshilfe HNO Innere Medizin Kardiologie Neurologie Onkologie und Hämatologie Orthopädie und Unfallchirurgie Pädiatrie Pathologie Psychiatrie Radiologie Rechtsmedizin Urologie Zahnmedizin
Themen
Klimawandel und Gesundheit Neues aus dem Markt COVID-19 Praxis und Beruf Seltene Erkrankungen GOÄ & EBM Panorama
Sammlungen
Kasuistiken Algorithmen & Infografiken Blickdiagnosen Arthropedia FlapFinder (für Dermatochirurgen) Videos Kongressberichterstattung Medizin für Apothekerinnen und Apotheker Für Ärztinnen und Ärzte in Weiterbildung Für Medizinstudierende
Erweiterte Suche
Anmelden
nach oben
Seminars in Immunopathology
Erschienen in: Seminars in Immunopathology 1/2014

01.01.2014 | Review

CEACAM1 loss links inflammation to insulin resistance in obesity and non-alcoholic steatohepatitis (NASH)

verfasst von: Sonia M. Najjar, Lucia Russo

Erschienen in: Seminars in Immunopathology | Ausgabe 1/2014

Einloggen, um Zugang zu erhalten

Abstract

Mounting epidemiological evidence points to an association between metabolic syndrome and non-alcoholic steatohepatitis (NASH), an increasingly recognized new epidemic. NASH pathologies include hepatocellular ballooning, lobular inflammation, hepatocellular injury, apoptosis, and hepatic fibrosis. We will review the relationship between insulin resistance and inflammation in visceral obesity and NASH in an attempt to shed more light on the pathogenesis of these major metabolic diseases. Moreover, we will identify loss of the carcinoembryonic antigen-related cell adhesion molecule 1 as a unifying mechanism linking the immunological and metabolic abnormalities in NASH.
Literatur
1.
2.
3.
4.
5.
6.
Osborn O, Olefsky JM (2012) The cellular and signaling networks linking the immune system and metabolism in disease. Nat Med 18(3):363–374. doi:10.​1038/​nm.​2627 PubMed
7.
8.
9.
Poy MN, Yang Y, Rezaei K, Fernstrom MA, Lee AD, Kido Y, Erickson SK, Najjar SM (2002) CEACAM1 regulates insulin clearance in liver. Nat Genet 30(3):270–276. doi:10.​1038/​ng840 PubMed
10.
DeAngelis AM, Heinrich G, Dai T, Bowman TA, Patel PR, Lee SJ, Hong EG, Jung DY, Assmann A, Kulkarni RN, Kim JK, Najjar SM (2008) Carcinoembryonic antigen-related cell adhesion molecule 1: a link between insulin and lipid metabolism. Diabetes 57(9):2296–2303. doi:10.​2337/​db08-0379 PubMed
11.
Choi SS, Diehl AM (2008) Hepatic triglyceride synthesis and nonalcoholic fatty liver disease. Curr Opin Lipidol 19(3):295–300PubMed
12.
DeFronzo RA (1988) Lilly lecture, 1987. The triumvirate: beta-cell, muscle, liver. A collusion responsible for NIDDM. Diabetes Care 37(6):667–687
13.
Bergman RN, Ader M (2000) Free fatty acids and pathogenesis of type 2 diabetes mellitus. Trends Endocrinol Metab 11(9):351–356PubMed
14.
Hotamisligil GS, Shargill NS, Spiegelman BM (1993) Adipose expression of tumor necrosis factor-alpha: direct role in obesity-linked insulin resistance. Science 259(5091):87–91PubMed
15.
Steppan CM, Bailey ST, Bhat S, Brown EJ, Banerjee RR, Wright CM, Patel HR, Ahima RS, Lazar MA (2001) The hormone resistin links obesity to diabetes. Nature 409(6818):307–312. doi:10.​1038/​35053000 PubMed
16.
Berg AH, Combs TP, Du X, Brownlee M, Scherer PE (2001) The adipocyte-secreted protein Acrp30 enhances hepatic insulin action. Nat Med 7(8):947–953. doi:10.​1038/​90992 PubMed
17.
18.
Hotamisligil GS, Shargill NS, Spiegelman BM (1993) Adipose expression of tumor necrosis factor-alpha: direct role in obesity-linked insulin resistance. Science 259:87–91PubMed
19.
Hotamisligil GS, Arner P, Caro JF, Atkinson RL, Spiegelman BM (1995) Increased adipose tissue expression of tumor necrosis factor-alpha in human obesity and insulin resistance. J Clin Invest 95(5):2409–2415. doi:10.​1172/​JCI117936 PubMedPubMedCentral
20.
Hotamisligil GS, Peraldi P, Budavari A, Ellis R, White MF, Spiegelman BM (1996) IRS-1-mediated inhibition of insulin receptor tyrosine kinase activity in TNF-alpha- and obesity-induced insulin resistance. Science 271(5249):665–668PubMed
21.
Fain JN, Cheema PS, Bahouth SW, Lloyd Hiler M (2003) Resistin release by human adipose tissue explants in primary culture. Biochem Biophys Res Commun 300(3):674–678PubMed
22.
Weisberg SP, McCann D, Desai M, Rosenbaum M, Leibel R, Ferrante AWJ (2003) Obesity is associated with macrophage accumulation in adipose tissue. J Clin Invest 112:1796–1808PubMedPubMedCentral
23.
Xu H, Barnes GT, Yang Q, Tan G, Yang D, Chou CJ, Sole J, Nichols A, Ross JS, Tartaglia LA, Chen H (2003) Chronic inflammation in fat plays a crucial role in the development of obesity-related insulin resistance. J Clin Invest 112:1821–1830PubMedPubMedCentral
24.
25.
Xu H, Barnes GT, Yang Q, Tan G, Yang D, Chou CJ, Sole J, Nichols A, Ross JS, Tartaglia LA, Chen H (2003) Chronic inflammation in fat plays a crucial role in the development of obesity-related insulin resistance. J Clin Invest 112(12):1821–1830. doi:10.​1172/​JCI19451 PubMedPubMedCentral
26.
27.
28.
Takahashi K, Mizuarai S, Araki H, Mashiko S, Ishihara A, Kanatani A, Itadani H, Kotani H (2003) Adiposity elevates plasma MCP-1 levels leading to the increased CD11b-positive monocytes in mice. J Biol Chem 278(47):46654–46660. doi:10.​1074/​jbc.​M309895200 PubMed
29.
30.
Winer S, Chan Y, Paltser G, Truong D, Tsui H, Bahrami J, Dorfman R, Wang Y, Zielenski J, Mastronardi F, Maezawa Y, Drucker DJ, Engleman E, Winer D, Dosch HM (2009) Normalization of obesity-associated insulin resistance through immunotherapy. Nat Med 15(8):921–929. doi:10.​1038/​nm.​2001 PubMedPubMedCentral
31.
Wu D, Molofsky AB, Liang HE, Ricardo-Gonzalez RR, Jouihan HA, Bando JK, Chawla A, Locksley RM (2011) Eosinophils sustain adipose alternatively activated macrophages associated with glucose homeostasis. Science 332(6026):243–247. doi:10.​1126/​science.​1201475 PubMedPubMedCentral
32.
Talukdar S, da Oh Y, Bandyopadhyay G, Li D, Xu J, McNelis J, Lu M, Li P, Yan Q, Zhu Y, Ofrecio J, Lin M, Brenner MB, Olefsky JM (2012) Neutrophils mediate insulin resistance in mice fed a high-fat diet through secreted elastase. Nat Med 18(9):1407–1412. doi:10.​1038/​nm.​2885 PubMedPubMedCentral
33.
Han MS, Jung DY, Morel C, Lakhani SA, Kim JK, Flavell RA, Davis RJ (2013) JNK expression by macrophages promotes obesity-induced insulin resistance and inflammation. Science 339(6116):218–222. doi:10.​1126/​science.​1227568 PubMed
34.
35.
36.
37.
38.
Tataranni PA, Ortega E (2005) A burning question: does an adipokine-induced activation of the immune system mediate the effect of overnutrition on type 2 diabetes? Diabetes 54(4):917–927PubMed
39.
Chen J, Wildman RP, Hamm LL, Muntner P, Reynolds K, Whelton PK, He J (2004) Association between inflammation and insulin resistance in U.S. nondiabetic adults: results from the Third National Health and Nutrition Examination Survey. Diabetes Care 27:2960–2965PubMed
40.
Calle EE, Rodriguez C, Walker-Thurmond K, Thun MJ (2003) Overweight, obesity, and mortality from cancer in a prospectively studied cohort of U.S. adults. N Engl J Med 348:1625–1638PubMed
41.
Uysal KT, Wiesbrock SM, Marino MW, Hotamisligil GS (1997) Protection from obesity-induced insulin resistance in mice lacking TNF-alpha function. Nature 389(6651):610–614. doi:10.​1038/​39335 PubMed
42.
Yuan M, Konstantopoulos N, Lee J, Hansen L, Li ZW, Karin M, Shoelson SE (2001) Reversal of obesity- and diet-induced insulin resistance with salicylates or targeted disruption of Ikkbeta. Science 293(5535):1673–1677. doi:10.​1126/​science.​1061620 PubMed
43.
Perreault M, Marette A (2001) Targeted disruption of inducible nitric oxide synthase protects against obesity-linked insulin resistance in muscle. Nat Med 7(10):1138–1143. doi:10.​1038/​nm1001-1138 PubMed
44.
Hirosumi J, Tuncman G, Chang L, Gorgun CZ, Uysal KT, Maeda K, Karin M, Hotamisligil GS (2002) A central role for JNK in obesity and insulin resistance. Nature 420(6913):333–336. doi:10.​1038/​nature01137 PubMed
45.
Cai D, Yuan M, Frantz DF, Melendez PA, Hansen L, Lee J, Shoelson SE (2005) Local and systemic insulin resistance resulting from hepatic activation of IKK-beta and NF-kappaB. Nat Med 11(2):183–190. doi:10.​1038/​nm1166 PubMedPubMedCentral
46.
Frayn KN (2000) Visceral fat and insulin resistance—causative or correlative? Br J Nutr 83(Suppl 1):S71–S77PubMed
47.
48.
Coppack SW, Evans RD, Fisher RM, Frayn KN, Gibbons GF, Humphreys SM, Kirk ML, Potts JL, Hockaday TD (1992) Adipose tissue metabolism in obesity: lipase action in vivo before and after a mixed meal. Metabolism 41:264–272PubMed
49.
Sykiotis GP, Papavassiliou AG (2001) Serine phosphorylation of insulin receptor substrate-1: a novel target for the reversal of insulin resistance. Mol Endocrinol 15:1864–1869PubMed
50.
Le Marchand-Brustel Y, Gual P, Gremeaux T, Gonzalez T, Barres R, Tanti JF (2003) Fatty acid-induced insulin resistance: role of insulin receptor substrate 1 serine phosphorylation in the retroregulation of insulin signalling. Biochem Soc Trans 31:1152–1156PubMed
51.
52.
53.
Le Marchand-Brustel Y, Gual P, Gremeaux T, Gonzalez T, Barres R, Tanti JF (2003) Fatty acid-induced insulin resistance: role of insulin receptor substrate 1 serine phosphorylation in the retroregulation of insulin signalling. Biochem Soc Trans 31(Pt 6):1152–1156. doi:10.​1042/​ PubMed
54.
Cai D, Yuan M, Frantz DF, Melendez PA, Hansen L, Lee J, Shoelson SE (2005) Local and systemic insulin resistance resulting from hepatic activation of IKK-beta and NF-kappaB. Nat Med 11:183–190PubMedPubMedCentral
55.
Lang CH, Dobrescu C, Bagby GJ (1992) Tumor necrosis factor impairs insulin action on peripheral glucose disposal and hepatic glucose output. Endocrinology 130(1):43–52PubMed
56.
Porter MH, Cutchins A, Fine JB, Bai Y, DiGirolamo M (2002) Effects of TNF-alpha on glucose metabolism and lipolysis in adipose tissue and isolated fat-cell preparations. J Lab Clin Med 139(3):140–146PubMed
57.
Feinstein R, Kanety H, Papa MZ, Lunenfeld B, Karasik A (1993) Tumor necrosis factor-alpha suppresses insulin-induced tyrosine phosphorylation of insulin receptor and its substrates. J Biol Chem 268(35):26055–26058PubMed
58.
Hutley L, Prins JB (2005) Fat as an endocrine organ: relationship to the metabolic syndrome. Am J Med Sci 330(6):280–289PubMed
59.
Gwechenberger M, Mendoza LH, Youker KA, Frangogiannis NG, Smith CW, Michael LH, Entman ML (1999) Cardiac myocytes produce interleukin-6 in culture and in viable border zone of reperfused infarctions. Circulation 99(4):546–551PubMed
60.
Bastard JP, Maachi M, Van Nhieu JT, Jardel C, Bruckert E, Grimaldi A, Robert JJ, Capeau J, Hainque B (2002) Adipose tissue IL-6 content correlates with resistance to insulin activation of glucose uptake both in vivo and in vitro. J Clin Endocrinol Metab 87(5):2084–2089PubMed
61.
Fontana L, Eagon JC, Trujillo ME, Scherer PE, Klein S (2007) Visceral fat adipokine secretion is associated with systemic inflammation in obese humans. Diabetes 56(4):1010–1013. doi:10.​2337/​db06-1656 PubMed
62.
Senn JJ, Klover PJ, Nowak IA, Zimmers TA, Koniaris LG, Furlanetto RW, Mooney RA (2003) Suppressor of cytokine signaling-3 (SOCS-3), a potential mediator of interleukin-6-dependent insulin resistance in hepatocytes. J Biol Chem 278(16):13740–13746. doi:10.​1074/​jbc.​M210689200 PubMed
63.
Matthews VB, Allen TL, Risis S, Chan MH, Henstridge DC, Watson N, Zaffino LA, Babb JR, Boon J, Meikle PJ, Jowett JB, Watt MJ, Jansson JO, Bruce CR, Febbraio MA (2010) Interleukin-6-deficient mice develop hepatic inflammation and systemic insulin resistance. Diabetologia 53(11):2431–2441. doi:10.​1007/​s00125-010-1865-y PubMed
64.
Wallenius V, Wallenius K, Ahren B, Rudling M, Carlsten H, Dickson SL, Ohlsson C, Jansson JO (2002) Interleukin-6-deficient mice develop mature-onset obesity. Nat Med 8(1):75–79. doi:10.​1038/​nm0102-75 PubMed
65.
66.
Jansson JO, Wallenius K, Wernstedt I, Ohlsson C, Dickson SL, Wallenius V (2003) On the site and mechanism of action of the anti-obesity effects of interleukin-6. Growth Horm IGF Res 13 Suppl A:S28-32
67.
Franckhauser S, Elias I, Rotter Sopasakis V, Ferre T, Nagaev I, Andersson CX, Agudo J, Ruberte J, Bosch F, Smith U (2008) Overexpression of Il6 leads to hyperinsulinaemia, liver inflammation and reduced body weight in mice. Diabetologia 51(7):1306–1316. doi:10.​1007/​s00125-008-0998-8 PubMed
68.
Zhang Y, Proenca R, Maffei M, Barone M, Leopold L, Friedman JM (1994) Positional cloning of the mouse obese gene and its human homologue. Nature 372(6505):425–432. doi:10.​1038/​372425a0 PubMed
69.
Mantzoros CS (1999) The role of leptin in human obesity and disease: a review of current evidence. Ann Intern Med 130(8):671–680PubMed
70.
Lord GM, Matarese G, Howard JK, Baker RJ, Bloom SR, Lechler RI (1998) Leptin modulates the T-cell immune response and reverses starvation-induced immunosuppression. Nature 394(6696):897–901. doi:10.​1038/​29795 PubMed
71.
Matarese G, Moschos S, Mantzoros CS (2005) Leptin in immunology. J Immunol 174(6):3137–3142PubMed
72.
Aleffi S, Petrai I, Bertolani C, Parola M, Colombatto S, Novo E, Vizzutti F, Anania FA, Milani S, Rombouts K, Laffi G, Pinzani M, Marra F (2005) Upregulation of proinflammatory and proangiogenic cytokines by leptin in human hepatic stellate cells. Hepatology 42(6):1339–1348. doi:10.​1002/​hep.​20965 PubMed
73.
Gan L, Guo K, Cremona ML, McGraw TE, Leibel RL, Zhang Y (2012) TNF-alpha up-regulates protein level and cell surface expression of the leptin receptor by stimulating its export via a PKC-dependent mechanism. Endocrinology 153(12):5821–5833. doi:10.​1210/​en.​2012-1510 PubMed
74.
Kadowaki T, Yamauchi T, Kubota N, Hara K, Ueki K, Tobe K (2006) Adiponectin and adiponectin receptors in insulin resistance, diabetes, and the metabolic syndrome. J Clin Invest 116(7):1784–1792. doi:10.​1172/​JCI29126 PubMedPubMedCentral
75.
Yamauchi T, Kamon J, Minokoshi Y, Ito Y, Waki H, Uchida S, Yamashita S, Noda M, Kita S, Ueki K, Eto K, Akanuma Y, Froguel P, Foufelle F, Ferre P, Carling D, Kimura S, Nagai R, Kahn BB, Kadowaki T (2002) Adiponectin stimulates glucose utilization and fatty-acid oxidation by activating AMP-activated protein kinase. Nat Med 8(11):1288–1295. doi:10.​1038/​nm788 PubMed
76.
77.
Maeda N, Takahashi M, Funahashi T, Kihara S, Nishizawa H, Kishida K, Nagaretani H, Matsuda M, Komuro R, Ouchi N, Kuriyama H, Hotta K, Nakamura T, Shimomura I, Matsuzawa Y (2001) PPARgamma ligands increase expression and plasma concentrations of adiponectin, an adipose-derived protein. Diabetes 50(9):2094–2099PubMed
78.
Yokota T, Oritani K, Takahashi I, Ishikawa J, Matsuyama A, Ouchi N, Kihara S, Funahashi T, Tenner AJ, Tomiyama Y, Matsuzawa Y (2000) Adiponectin, a new member of the family of soluble defense collagens, negatively regulates the growth of myelomonocytic progenitors and the functions of macrophages. Blood 96(5):1723–1732PubMed
79.
Takemura Y, Ouchi N, Shibata R, Aprahamian T, Kirber MT, Summer RS, Kihara S, Walsh K (2007) Adiponectin modulates inflammatory reactions via calreticulin receptor-dependent clearance of early apoptotic bodies. J Clin Invest 117(2):375–386. doi:10.​1172/​JCI29709 PubMedPubMedCentral
80.
Wilk S, Jenke A, Stehr J, Yang CA, Bauer S, Goldner K, Kotsch K, Volk HD, Poller W, Schultheiss HP, Skurk C, Scheibenbogen C (2013) Adiponectin modulates NK-cell function. Eur J Immunol 43(4):1024–1033. doi:10.​1002/​eji.​201242382 PubMed
81.
Maeda N, Shimomura I, Kishida K, Nishizawa H, Matsuda M, Nagaretani H, Furuyama N, Kondo H, Takahashi M, Arita Y, Komuro R, Ouchi N, Kihara S, Tochino Y, Okutomi K, Horie M, Takeda S, Aoyama T, Funahashi T, Matsuzawa Y (2002) Diet-induced insulin resistance in mice lacking adiponectin/ACRP30. Nat Med 8(7):731–737. doi:10.​1038/​nm724 PubMed
82.
Ajuwon KM, Spurlock ME (2005) Adiponectin inhibits LPS-induced NF-kappaB activation and IL-6 production and increases PPARgamma2 expression in adipocytes. Am J Physiol Regul Integr Comp Physiol 288(5):R1220–R1225. doi:10.​1152/​ajpregu.​00397.​2004 PubMed
83.
Bugianesi E, McCullough AJ, Marchesini G (2005) Insulin resistance: a metabolic pathway to chronic liver disease. Hepatology 42(5):987–1000. doi:10.​1002/​hep.​20920 PubMed
84.
85.
Kumada M, Kihara S, Ouchi N, Kobayashi H, Okamoto Y, Ohashi K, Maeda K, Nagaretani H, Kishida K, Maeda N, Nagasawa A, Funahashi T, Matsuzawa Y (2004) Adiponectin specifically increased tissue inhibitor of metalloproteinase-1 through interleukin-10 expression in human macrophages. Circulation 109(17):2046–2049. doi:10.​1161/​01.​CIR.​0000127953.​98131.​ED PubMed
86.
87.
Boden G (2006) Fatty acid-induced inflammation and insulin resistance in skeletal muscle and liver. Curr Diab Rep 6:177–181PubMed
88.
Reaven GM (1995) Pathophysiology of insulin resistance in human disease. Physiol Rev 75:473–486PubMed
89.
Baldeweg SE, Golay A, Natali A, Balkau B, Del Prato S, Coppack SW (2000) Insulin resistance, lipid and fatty acid concentrations in 867 healthy Europeans. European Group for the Study of Insulin Resistance (EGIR). Eur J Clin Invest 30:45–52PubMed
90.
Charles MA, Eschwege E, Thibult N, Claude JR, Warnet JM, Rosselin GE, Girard J, Balkau B (1997) The role of non-esterified fatty acids in the deterioration of glucose tolerance in Caucasian subjects: results of the Paris Prospective Study. Diabetologia 40:1101–1106PubMed
91.
Knowler WC, Barrett-Connor E, Fowler SE, Hamman RF, Lachin JM, Walker EA, Nathan DM (2002) Reduction in the incidence of type 2 diabetes with lifestyle intervention or metformin. N Engl J Med 346(6):393–403. doi:10.​1056/​NEJMoa012512 PubMed
92.
Ostman J, Arner P, Engfeldt P, Kager L (1979) Regional differences in the control of lipolysis in human adipose tissue. Metabolism 28:1198–1205PubMed
93.
Lewis GF, Carpentier A, Adeli K, Giacca A (2002) Disordered fat storage and mobilization in the pathogenesis of insulin resistance and type 2 diabetes. Endocr Rev 23(2):201–229PubMed
94.
Ferre P (2004) The biology of peroxisome proliferator-activated receptors: relationship with lipid metabolism and insulin sensitivity. Diabetes 53(Suppl 1):S43–S50PubMed
95.
Boden G (1997) Role of fatty acids in the pathogenesis of insulin resistance and NIDDM. Diabetes 46:3–10PubMed
96.
Bergman RN, Ader M (2000) Free fatty acids and pathogenesis of type 2 diabetes mellitus. Trends Endocrinol Metab 11:351–356PubMed
97.
Rebrin K, Steil GM, Getty L, Bergman RN (1995) Free fatty acid as a link in the regulation of hepatic glucose output by peripheral insulin. Diabetes 44(9):1038–1045PubMed
98.
Bays H, Mandarino L, DeFronzo RA (2004) Role of the adipocyte, free fatty acids, and ectopic fat in pathogenesis of type 2 diabetes mellitus: peroxisomal proliferator-activated receptor agonists provide a rational therapeutic approach. J Clin Endocrinol Metab 89:463–478, ReviewPubMed
99.
Kabir M, Catalano KJ, Ananthnarayan S, Kim SP, Van Citters GW, Dea MK, Bergman RN (2005) Molecular evidence supporting the portal theory: a causative link between visceral adiposity and hepatic insulin resistance. Am J Physiol Endocrinol Metab 288(2):E454–E461. doi:10.​1152/​ajpendo.​00203.​2004 PubMed
100.
Williamson JR, Kreisberg RA, Felts PW (1966) Mechanism for the stimulation of gluconeogenesis by fatty acids in perfused rat liver. Proc Natl Acad Sci U S A 56:247–254PubMedPubMedCentral
101.
Massillon D, Barzilai N, Hawkins M, Prus-Wertheimer D, Rossetti L (1997) Induction of hepatic glucose-6-phosphatase gene expression by lipid infusion. Diabetes 46(1):153–157PubMed
102.
Oakes ND, Cooney GJ, Camilleri S, Chisholm DJ, Kraegen EW (1997) Mechanisms of liver and muscle insulin resistance induced by chronic high-fat feeding. Diabetes 46:1768–1774PubMed
103.
Sidossis LS, Mittendorfer B, Walser E, Chinkes D, Wolfe RR (1998) Hyperglycemia-induced inhibition of splanchnic fatty acid oxidation increases hepatic triacylglycerol secretion. Am J Physiol 275:E798–E805PubMed
104.
Boden G, Cheung P, Stein TP, Kresge K, Mozzoli M (2002) FFA cause hepatic insulin resistance by inhibiting insulin suppression of glycogenolysis. Am J Physiol Endocrinol Metab 283(1):E12–E19. doi:10.​1152/​ajpendo.​00429.​2001 PubMed
105.
Mittelman SD, Van Citters GW, Kim SP, Davis DA, Dea MK, Hamilton-Wessler M, Bergman RN (2000) Longitudinal compensation for fat-induced insulin resistance includes reduced insulin clearance and enhanced beta-cell response. Diabetes 49:2116–2125PubMed
106.
Randle PJ, Hales CN, Garland PB, Newsholm EA (1963) The glucose-fatty acid cycle: its role in insulin sensitivity and the metabolic disturbances of diabetes mellitus. Lancet 1:785–789PubMed
107.
Freedland ES (2004) Role of a critical visceral adipose tissue threshold (CVATT) in metabolic syndrome: implications for controlling dietary carbohydrates: a review. Nutr Metab (Lond) 1:12
108.
Freedland ES (2004) Role of a critical visceral adipose tissue threshold (CVATT) in metabolic syndrome: implications for controlling dietary carbohydrates: a review. Nutr Metab (Lond) 1(1):12. doi:10.​1186/​1743-7075-1-12
109.
Kim YB, Kotani K, Ciaraldi TP, Henry RR, Kahn BB (2003) Insulin-stimulated protein kinase C lambda/zeta activity is reduced in skeletal muscle of humans with obesity and type 2 diabetes: reversal with weight reduction. Diabetes 52:1935–1942PubMed
110.
Nguyen MT, Satoh H, Favelyukis S, Babendure JL, Imamura T, Sbodio JI, Zalevsky J, Dahiyat BI, Chi NW, Olefsky JM (2005) JNK and tumor necrosis factor-alpha mediate free fatty acid-induced insulin resistance in 3T3-L1 adipocytes. J Biol Chem 280(42):35361–35371. doi:10.​1074/​jbc.​M504611200 PubMed
111.
112.
113.
114.
115.
Powell EE, Cooksley WG, Hanson R, Searle J, Halliday JW, Powell LW (1990) The natural history of nonalcoholic steatohepatitis: a follow-up study of forty-two patients for up to 21 years. Hepatology 11(1):74–80PubMed
116.
Hui JM, Kench JG, Chitturi S, Sud A, Farrell GC, Byth K, Hall P, Khan M, George J (2003) Long-term outcomes of cirrhosis in nonalcoholic steatohepatitis compared with hepatitis C. Hepatology 38(2):420–427. doi:10.​1053/​jhep.​2003.​50320 PubMed
117.
Neuschwander-Tetri BA (2005) Nonalcoholic steatohepatitis and the metabolic syndrome. Am J Med Sci 330(6):326–335PubMed
118.
Brunt EM (2005) Nonalcoholic steatohepatitis: pathologic features and differential diagnosis. Semin Diagn Pathol 22:330–338PubMed
119.
Kleiner DE, Brunt EM, Van Natta M, Behling C, Contos MJ, Cummings OW, Ferrell LD, Liu YC, Torbenson MS, Unalp-Arida A, Yeh M, McCullough AJ, Sanyal AJ (2005) Design and validation of a histological scoring system for nonalcoholic fatty liver disease. Hepatology 41(6):1313–1321. doi:10.​1002/​hep.​20701 PubMed
120.
121.
122.
Day CP, James OF (1998) Steatohepatitis: a tale of two “hits”? Gastroenterology 114:842–845PubMed
123.
Day CP (2002) Pathogenesis of steatohepatitis. Best Pract Res Clin Gastroenterol 16(5):663–678PubMed
124.
Marchesini G, Bugianesi E, Forlani G, Cerrelli F, Lenzi M, Manini R, Natale S, Vanni E, Villanova N, Melchionda N, Rizzetto M (2003) Nonalcoholic fatty liver, steatohepatitis, and the metabolic syndrome. Hepatology 37(4):917–923. doi:10.​1053/​jhep.​2003.​50161 PubMed
125.
Adams LA, Lymp JF, St Sauver J, Sanderson SO, Lindor KD, Feldstein A, Angulo P (2005) The natural history of nonalcoholic fatty liver disease: a population-based cohort study. Gastroenterology 129:113–121PubMed
126.
Marra F, Gastaldelli A, Svegliati Baroni G, Tell G, Tiribelli C (2008) Molecular basis and mechanisms of progression of non-alcoholic steatohepatitis. Trends Mol Med 14:72–81PubMed
127.
128.
129.
Fisher EA, Ginsberg HN (2002) Complexity in the secretory pathway: the assembly and secretion of apolipoprotein B-containing lipoproteins. J Biol Chem 277(20):17377–17380PubMed
130.
131.
132.
Takahashi Y, Fukusato T (2010) Pediatric nonalcoholic fatty liver disease: overview with emphasis on histology. World J Gastroenterol 16(42):5280–5285PubMed
133.
Eguchi Y, Hyogo H, Ono M, Mizuta T, Ono N, Fujimoto K, Chayama K, Saibara T (2012) Prevalence and associated metabolic factors of nonalcoholic fatty liver disease in the general population from 2009 to 2010 in Japan: a multicenter large retrospective study. J Gastroenterol 47(5):586–595. doi:10.​1007/​s00535-012-0533-z PubMed
134.
135.
Eberle D, Hegarty B, Bossard P, Ferre P, Foufelle F (2004) SREBP transcription factors: master regulators of lipid homeostasis. Biochimie 86(11):839–848PubMed
136.
137.
Green RM (2003) NASH—hepatic metabolism and not simply the metabolic syndrome. Hepatology 38(1):14–17PubMed
138.
Abdelmalek MF, Diehl AM (2007) Nonalcoholic fatty liver disease as a complication of insulin resistance. Med Clin North Am 91:1125–1149, ixPubMed
139.
Otogawa K, Kinoshita K, Fujii H, Sakabe M, Shiga R, Nakatani K, Ikeda K, Nakajima Y, Ikura Y, Ueda M, Arakawa T, Hato F, Kawada N (2007) 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 170:967–980PubMed
140.
Leclercq IA, Farrell GC, Schriemer R, Robertson GR (2002) Leptin is essential for the hepatic fibrogenic response to chronic liver injury. J Hepatol 37(2):206–213PubMed
141.
142.
Nakayama H, Otabe S, Ueno T, Hirota N, Yuan X, Fukutani T, Hashinaga T, Wada N, Yamada K (2007) Transgenic mice expressing nuclear sterol regulatory element-binding protein 1c in adipose tissue exhibit liver histology similar to nonalcoholic steatohepatitis. Metabolism 56:470–475PubMed
143.
144.
Svegliati-Baroni G, Candelaresi C, Saccomanno S, Ferretti G, Bachetti T, Marzioni M, De Minicis S, Nobili L, Salzano R, Omenetti A, Pacetti D, Sigmund S, Benedetti A, Casini A (2006) A model of insulin resistance and nonalcoholic steatohepatitis in rats: role of peroxisome proliferator-activated receptor-alpha and n-3 polyunsaturated fatty acid treatment on liver injury. Am J Pathol 169(3):846–860PubMed
145.
Rinella ME, Green RM (2004) The methionine-choline deficient dietary model of steatohepatitis does not exhibit insulin resistance. J Hepatol 40:47–51PubMed
146.
Lieber CS (2004) CYP2E1: from ASH to NASH. Hepatol Res 28:1–11PubMed
147.
Matsuzawa N, Takamura T, Kurita S, Misu H, Ota T, Ando H, Yokoyama M, Honda M, Zen Y, Nakanuma Y, Miyamoto K, Kaneko S (2007) Lipid-induced oxidative stress causes steatohepatitis in mice fed an atherogenic diet. Hepatology 46(5):1392–1403. doi:10.​1002/​hep.​21874 PubMed
148.
149.
150.
Colicchio P, Tarantino G, del Genio F, Sorrentino P, Saldalamacchia G, Finelli C, Conca P, Contaldo F, Pasanisi F (2005) Non-alcoholic fatty liver disease in young adult severely obese non-diabetic patients in South Italy. Ann Nutr Metab 49(5):289–295. doi:10.​1159/​000087295 PubMed
151.
152.
Bertola A, Bonnafous S, Anty R, Patouraux S, Saint-Paul MC, Iannelli A, Gugenheim J, Barr J, Mato JM, Le Marchand-Brustel Y, Tran A, Gual P (2010) Hepatic expression patterns of inflammatory and immune response genes associated with obesity and NASH in morbidly obese patients. PLoS One 5(10):e13577. doi:10.​1371/​journal.​pone.​0013577 PubMedPubMedCentral
153.
Pacifico L, Di Renzo L, Anania C, Osborn JF, Ippoliti F, Schiavo E, Chiesa C (2006) Increased T-helper interferon-gamma-secreting cells in obese children. Eur J Endocrinol 154(5):691–697. doi:10.​1530/​eje.​1.​02138 PubMed
154.
Chakravarthy MV, Pan Z, Zhu Y, Tordjman K, Schneider JG, Coleman T, Turk J, Semenkovich CF (2005) “New” hepatic fat activates PPARalpha to maintain glucose, lipid, and cholesterol homeostasis. Cell Metab 1(5):309–322. doi:10.​1016/​j.​cmet.​2005.​04.​002 PubMed
155.
Chavin KD, Yang S, Lin HZ, Chatham J, Chacko VP, Hoek JB, Walajtys-Rode E, Rashid A, Chen CH, Huang CC, Wu TC, Lane MD, Diehl AM (1999) Obesity induces expression of uncoupling protein-2 in hepatocytes and promotes liver ATP depletion. J Biol Chem 274:5692–5700PubMed
156.
Arkan MC, Hevener AL, Greten FR, Maeda S, Li ZW, Long JM, Wynshaw-Boris A, Poli G, Olefsky J, Karin M (2005) IKK-beta links inflammation to obesity-induced insulin resistance. Nat Med 11:191–198PubMed
157.
Fernandez-Checa JC, Kaplowitz N, Garcia-Ruiz C, Colell A, Miranda M, Mari M, Ardite E, Morales A (1997) GSH transport in mitochondria: defense against TNF-induced oxidative stress and alcohol-induced defect. Am J Physiol 273:G7–G17PubMed
158.
Dela Pena A, Leclercq I, Field J, George J, Jones B, Farrell G (2005) NF-kappaB activation, rather than TNF, mediates hepatic inflammation in a murine dietary model of steatohepatitis. Gastroenterology 129:1663–1674PubMed
159.
Day CP (2006) From fat to inflammation. Gastroenterology 130:207–210PubMed
160.
McClain CJ, Mokshagundam SP, Barve SS, Song Z, Hill DB, Chen T, Deaciuc I (2004) Mechanisms of non-alcoholic steatohepatitis. Alcohol 34:67–79PubMed
161.
162.
Rutkowski DT, Wu J, Back SH, Callaghan MU, Ferris SP, Iqbal J, Clark R, Miao H, Hassler JR, Fornek J, Katze MG, Hussain MM, Song B, Swathirajan J, Wang J, Yau GD, Kaufman RJ (2008) UPR pathways combine to prevent hepatic steatosis caused by ER stress-mediated suppression of transcriptional master regulators. Dev Cell 15(6):829–840. doi:10.​1016/​j.​devcel.​2008.​10.​015 PubMedPubMedCentral
163.
164.
Schattenberg JM, Singh R, Wang Y, Lefkowitch JH, Rigoli RM, Scherer PE, Czaja MJ (2006) JNK1 but not JNK2 promotes the development of steatohepatitis in mice. Hepatology 43(1):163–172. doi:10.​1002/​hep.​20999 PubMed
165.
Hirosumi J, Tuncman G, Chang L, Gorgun CZ, Uysal KT, Maeda K, Karin M, Hotamisligil GS (2002) A central role for JNK in obesity and insulin resistance. Nature 420:333–336PubMed
166.
167.
Dong Z, Wei H, Sun R, Tian Z (2007) The roles of innate immune cells in liver injury and regeneration. Cell Mol Immunol 4(4):241–252PubMed
168.
Diehl AM (2002) Nonalcoholic steatosis and steatohepatitis IV. Nonalcoholic fatty liver disease abnormalities in macrophage function and cytokines. Am J Physiol Gastrointest Liver Physiol 282(1):G1–G5. doi:10.​1152/​ajpgi.​00384.​2001 PubMed
169.
Tacke F (2012) Functional role of intrahepatic monocyte subsets for the progression of liver inflammation and liver fibrosis in vivo. Fibrogenesis Tissue Repair 5 Suppl 1:S27. doi:10.​1186/​1755-1536-5-S1-S27
170.
Odegaard JI, Ricardo-Gonzalez RR, Red Eagle A, Vats D, Morel CR, Goforth MH, Subramanian V, Mukundan L, Ferrante AW, Chawla A (2008) Alternative M2 activation of Kupffer cells by PPARdelta ameliorates obesity-induced insulin resistance. Cell Metab 7(6):496–507. doi:10.​1016/​j.​cmet.​2008.​04.​003 PubMedPubMedCentral
171.
Eguchi K, Manabe I, Oishi-Tanaka Y, Ohsugi M, Kono N, Ogata F, Yagi N, Ohto U, Kimoto M, Miyake K, Tobe K, Arai H, Kadowaki T, Nagai R (2012) Saturated fatty acid and TLR signaling link beta cell dysfunction and islet inflammation. Cell Metab 15(4):518–533. doi:10.​1016/​j.​cmet.​2012.​01.​023 PubMed
172.
Maina V, Sutti S, Locatelli I, Vidali M, Mombello C, Bozzola C, Albano E (2012) Bias in macrophage activation pattern influences non-alcoholic steatohepatitis (NASH) in mice. Clin Sci (Lond) 122(11):545–553. doi:10.​1042/​CS20110366
173.
174.
175.
176.
177.
Albano E, Mottaran E, Vidali M, Reale E, Saksena S, Occhino G, Burt AD, Day CP (2005) Immune response towards lipid peroxidation products as a predictor of progression of non-alcoholic fatty liver disease to advanced fibrosis. Gut 54(7):987–993. doi:10.​1136/​gut.​2004.​057968 PubMed
178.
179.
Hidaka T, Akada S, Teranishi A, Morikawa H, Sato S, Yoshida Y, Yajima A, Yaegashi N, Okamura K, Saito S (2003) Mirimostim (macrophage colony-stimulating factor; M-CSF) improves chemotherapy-induced impaired natural killer cell activity, Th1/Th2 balance, and granulocyte function. Cancer Sci 94(9):814–820PubMed
180.
Niemeyer M, Darmoise A, Mollenkopf HJ, Hahnke K, Hurwitz R, Besra GS, Schaible UE, Kaufmann SH (2008) Natural killer T-cell characterization through gene expression profiling: an account of versatility bridging T helper type 1 (Th1), Th2 and Th17 immune responses. Immunology 123(1):45–56. doi:10.​1111/​j.​1365-2567.​2007.​02701.​x PubMed
181.
182.
Kremer M, Hines IN (2008) Natural killer T cells and non-alcoholic fatty liver disease: fat chews on the immune system. World J Gastroenterol 14(3):487–488PubMed
183.
Xu CF, Yu CH, Li YM, Xu L, Du J, Shen Z (2007) Association of the frequency of peripheral natural killer T cells with nonalcoholic fatty liver disease. World J Gastroenterol 13(33):4504–4508PubMed
184.
Li Z, Soloski MJ, Diehl AM (2005) Dietary factors alter hepatic innate immune system in mice with nonalcoholic fatty liver disease. Hepatology 42:880–885PubMed
185.
Elinav E, Pappo O, Sklair-Levy M, Margalit M, Shibolet O, Gomori M, Alper R, Thalenfeld B, Engelhardt D, Rabbani E, Ilan Y (2006) Adoptive transfer of regulatory NKT lymphocytes ameliorates non-alcoholic steatohepatitis and glucose intolerance in ob/ob mice and is associated with intrahepatic CD8 trapping. J Pathol 209:121–128PubMed
186.
Tajiri K, Shimizu Y, Tsuneyama K, Sugiyama T (2009) Role of liver-infiltrating CD3+CD56+ natural killer T cells in the pathogenesis of nonalcoholic fatty liver disease. Eur J Gastroenterol Hepatol 21(6):673–680. doi:10.​1097/​MEG.​0b013e32831bc3d6​ PubMed
187.
Syn WK, Oo YH, Pereira TA, Karaca GF, Jung Y, Omenetti A, Witek RP, Choi SS, Guy CD, Fearing CM, Teaberry V, Pereira FE, Adams DH, Diehl AM (2010) Accumulation of natural killer T cells in progressive nonalcoholic fatty liver disease. Hepatology 51(6):1998–2007. doi:10.​1002/​hep.​23599 PubMedPubMedCentral
188.
van der Poorten D, Milner KL, Hui J, Hodge A, Trenell MI, Kench JG, London R, Peduto T, Chisholm DJ, George J (2008) Visceral fat: a key mediator of steatohepatitis in metabolic liver disease. Hepatology 48(2):449–457. doi:10.​1002/​hep.​22350 PubMed
189.
Tilg H, Hotamisligil GS (2006) Nonalcoholic fatty liver disease: cytokine–adipokine interplay and regulation of insulin resistance. Gastroenterology 131:934–945PubMed
190.
191.
Li Z, Yang S, Lin H, Huang J, Watkins PA, Moser AB, Desimone C, Song XY, Diehl AM (2003) Probiotics and antibodies to TNF inhibit inflammatory activity and improve nonalcoholic fatty liver disease. Hepatology 37:343–350PubMed
192.
Hui JM, Hodge A, Farrell GC, Kench JG, Kriketos A, George J (2004) Beyond insulin resistance in NASH: TNF-alpha or adiponectin? Hepatology 40(1):46–54. doi:10.​1002/​hep.​20280 PubMed
193.
Crespo J, Cayon A, Fernandez-Gil P, Hernandez-Guerra M, Mayorga M, Dominguez-Diez A, Fernandez-Escalante JC, Pons-Romero F (2001) Gene expression of tumor necrosis factor alpha and TNF-receptors, p55 and p75, in nonalcoholic steatohepatitis patients. Hepatology 34:1158–1163PubMed
194.
Manco M, Marcellini M, Giannone G, Nobili V (2007) Correlation of serum TNF-alpha levels and histologic liver injury scores in pediatric nonalcoholic fatty liver disease. Am J Clin Pathol 127:954–960PubMed
195.
Lesmana CR, Hasan I, Budihusodo U, Gani RA, Krisnuhoni E, Akbar N, Lesmana LA (2009) Diagnostic value of a group of biochemical markers of liver fibrosis in patients with non-alcoholic steatohepatitis. J Dig Dis 10(3):201–206. doi:10.​1111/​j.​1751-2980.​2009.​00386.​x PubMed
196.
Baranova A, Schlauch K, Elariny H, Jarrar M, Bennett C, Nugent C, Gowder SJ, Younoszai Z, Collantes R, Chandhoke V, Younossi ZM (2007) Gene expression patterns in hepatic tissue and visceral adipose tissue of patients with non-alcoholic fatty liver disease. Obes Surg 17(8):1111–1118PubMed
197.
198.
199.
Novobrantseva TI, Majeau GR, Amatucci A, Kogan S, Brenner I, Casola S, Shlomchik MJ, Koteliansky V, Hochman PS, Ibraghimov A (2005) Attenuated liver fibrosis in the absence of B cells. J Clin Invest 115(11):3072–3082. doi:10.​1172/​JCI24798 PubMedPubMedCentral
200.
Cressman DE, Greenbaum LE, DeAngelis RA, Ciliberto G, Furth EE, Poli V, Taub R (1996) Liver failure and defective hepatocyte regeneration in interleukin-6-deficient mice. Science 274(5291):1379–1383PubMed
201.
El-Assal O, Hong F, Kim WH, Radaeva S, Gao B (2004) IL-6-deficient mice are susceptible to ethanol-induced hepatic steatosis: IL-6 protects against ethanol-induced oxidative stress and mitochondrial permeability transition in the liver. Cell Mol Immunol 1(3):205–211PubMed
202.
Yamaguchi K, Itoh Y, Yokomizo C, Nishimura T, Niimi T, Fujii H, Okanoue T, Yoshikawa T (2010) Blockade of interleukin-6 signaling enhances hepatic steatosis but improves liver injury in methionine choline-deficient diet-fed mice. Lab Invest 90(8):1169–1178. doi:10.​1038/​labinvest.​2010.​75 PubMed
203.
204.
Chitturi S, Farrell G, Frost L, Kriketos A, Lin R, Fung C, Liddle C, Samarasinghe D, George J (2002) Serum leptin in NASH correlates with hepatic steatosis but not fibrosis: a manifestation of lipotoxicity? Hepatology 36(2):403–409. doi:10.​1053/​jhep.​2002.​34738 PubMed
205.
Ikejima K, Takei Y, Honda H, Hirose M, Yoshikawa M, Zhang YJ, Lang T, Fukuda T, Yamashina S, Kitamura T, Sato N (2002) Leptin receptor-mediated signaling regulates hepatic fibrogenesis and remodeling of extracellular matrix in the rat. Gastroenterology 122(5):1399–1410PubMed
206.
Potter JJ, Rennie-Tankesley L, Mezey E (2003) Influence of leptin in the development of hepatic fibrosis produced in mice by Schistosoma mansoni infection and by chronic carbon tetrachloride administration. J Hepatol 38(3):281–288PubMed
207.
208.
Chalasani N, Crabb DW, Cummings OW, Kwo PY, Asghar A, Pandya PK, Considine RV (2003) Does leptin play a role in the pathogenesis of human nonalcoholic steatohepatitis? Am J Gastroenterol 98:2771–2776PubMed
209.
Testa R, Franceschini R, Giannini E, Cataldi A, Botta F, Fasoli A, Tenerelli P, Rolandi E, Barreca T (2000) Serum leptin levels in patients with viral chronic hepatitis or liver cirrhosis. J Hepatol 33(1):33–37PubMed
210.
Musso G, Gambino R, Biroli G, Carello M, Faga E, Pacini G, De Michieli F, Cassader M, Durazzo M, Rizzetto M, Pagano G (2005) Hypoadiponectinemia predicts the severity of hepatic fibrosis and pancreatic Beta-cell dysfunction in nondiabetic nonobese patients with nonalcoholic steatohepatitis. Am J Gastroenterol 100(11):2438–2446. doi:10.​1111/​j.​1572-0241.​2005.​00297.​x PubMed
211.
Kaser S, Moschen A, Cayon A, Kaser A, Crespo J, Pons-Romero F, Ebenbichler CF, Patsch JR, Tilg H (2005) Adiponectin and its receptors in non-alcoholic steatohepatitis. Gut 54(1):117–121. doi:10.​1136/​gut.​2003.​037010 PubMed
212.
Bruun JM, Lihn AS, Verdich C, Pedersen SB, Toubro S, Astrup A, Richelsen B (2003) Regulation of adiponectin by adipose tissue-derived cytokines: in vivo and in vitro investigations in humans. Am J Physiol Endocrinol Metab 285(3):E527–E533. doi:10.​1152/​ajpendo.​00110.​2003 PubMed
213.
Engeli S, Feldpausch M, Gorzelniak K, Hartwig F, Heintze U, Janke J, Mohlig M, Pfeiffer AF, Luft FC, Sharma AM (2003) Association between adiponectin and mediators of inflammation in obese women. Diabetes 52(4):942–947PubMed
214.
Kern PA, Ranganathan S, Li C, Wood L, Ranganathan G (2001) Adipose tissue tumor necrosis factor and interleukin-6 expression in human obesity and insulin resistance. Am J Physiol Endocrinol Metab 280(5):E745–E751PubMed
215.
Moschen AR, Wieser V, Tilg H (2012) Adiponectin: key player in the adipose tissue-liver crosstalk. Curr Med Chem 19(32):5467–5473PubMed
216.
Xu A, Wang Y, Keshaw H, Xu LY, Lam KS, Cooper GJ (2003) The fat-derived hormone adiponectin alleviates alcoholic and nonalcoholic fatty liver diseases in mice. J Clin Invest 112(1):91–100. doi:10.​1172/​JCI17797 PubMedPubMedCentral
217.
218.
Öbrink B (1997) CEA adhesion molecules: multifunctional proteins with signal-regulatory properties. Curr Opin Cell Biol 9(5):616–626PubMed
219.
Najjar SM, Accili D, Philippe N, Jernberg J, Margolis R, Taylor SI (1993) pp 120/ecto-ATPase, an endogenous substrate of the insulin receptor tyrosine kinase, is expressed as two variably spliced isoforms. J Biol Chem 268:1201–1206PubMed
220.
221.
Gray-Owen SD, Blumberg RS (2006) CEACAM1: contact-dependent control of immunity. Nat Rev Immunol 6:433–446PubMed
222.
Markel G, Wolf D, Hanna J, Gazit R, Goldman-Wohl D, Lavy Y, Yagel S, Mandelboim O (2002) Pivotal role of CEACAM1 protein in the inhibition of activated decidual lymphocyte functions. J Clin Invest 110(7):943–953. doi:10.​1172/​JCI15643 PubMedPubMedCentral
223.
Chen CJ, Shively JE (2004) The cell-cell adhesion molecule carcinoembryonic antigen-related cellular adhesion molecule 1 inhibits IL-2 production and proliferation in human T cells by association with Src homology protein-1 and down-regulates IL-2 receptor. J Immunol 172:3544–3552PubMed
224.
225.
Nakajima A, Iijima H, Neurath MF, Nagaishi T, Nieuwenhuis EE, Raychowdhury R, Glickman J, Blau DM, Russell S, Holmes KV, Blumberg RS (2002) Activation-induced expression of carcinoembryonic antigen-cell adhesion molecule 1 regulates mouse T lymphocyte function. J Immunol 168(3):1028–1035PubMed
226.
Markel G, Lieberman N, Katz G, Arnon TI, Lotem M, Drize O, Blumberg RS, Bar-Haim E, Mader R, Eisenbach L, Mandelboim O (2002) CD66a interactions between human melanoma and NK cells: a novel class I MHC-independent inhibitory mechanism of cytotoxicity. J Immunol 168(6):2803–2810PubMed
227.
Iijima H, Neurath MF, Nagaishi T, Glickman JN, Nieuwenhuis EE, Nakajima A, Chen D, Fuss IJ, Utku N, Lewicki DN, Becker C, Gallagher TM, Holmes KV, Blumberg RS (2004) Specific regulation of T helper cell 1-mediated murine colitis by CEACAM1. J Exp Med 199(4):471–482. doi:10.​1084/​jem.​20030437 PubMedPubMedCentral
228.
Hosomi S, Chen Z, Baker K, Chen L, Huang YH, Olszak T, Zeissig S, Wang JH, Mandelboim O, Beauchemin N, Lanier LL, Blumberg RS (2013) CEACAM1 on activated NK cells inhibits NKG2D-mediated cytolytic function and signaling. Eur J Immunol. doi:10.​1002/​eji.​201242676 PubMed
229.
230.
Abraham RT, Weiss A (2004) Jurkat T cells and development of the T-cell receptor signalling paradigm. Nat Rev Immunol 4(4):301–308. doi:10.​1038/​nri1330 PubMed
231.
Coutelier JP, Godfraind C, Dveksler GS, Wysocka M, Cardellichio CB, Noel H, Holmes KV (1994) B lymphocyte and macrophage expression of carcinoembryonic antigen-related adhesion molecules that serve as receptors for murine coronavirus. Eur J Immunol 24(6):1383–1390. doi:10.​1002/​eji.​1830240622 PubMed
232.
Greicius G, Severinson E, Beauchemin N, Obrink B, Singer BB (2003) CEACAM1 is a potent regulator of B cell receptor complex-induced activation. J Leukoc Biol 74(1):126–134PubMed
233.
Chen T, Zimmermann W, Parker J, Chen I, Maeda A, Bolland S (2001) Biliary glycoprotein (BGPa, CD66a, CEACAM1) mediates inhibitory signals. J Leukoc Biol 70(2):335–340PubMed
234.
Lobo EO, Zhang Z, Shively JE (2009) Pivotal advance: CEACAM1 is a negative coreceptor for the B cell receptor and promotes CD19-mediated adhesion of B cells in a PI3K-dependent manner. J Leukoc Biol 86(2):205–218. doi:10.​1189/​jlb.​0109037 PubMed
235.
Kammerer R, Stober D, Singer BB, Obrink B, Reimann J (2001) Carcinoembryonic antigen-related cell adhesion molecule 1 on murine dendritic cells is a potent regulator of T cell stimulation. J Immunol 166(11):6537–6544PubMed
236.
237.
Boulton IC, Gray-Owen SD (2002) Neisserial binding to CEACAM1 arrests the activation and proliferation of CD4+ T lymphocytes. Nat Immunol 3(3):229–236. doi:10.​1038/​ni769 PubMed
238.
239.
Carpentier JL (1994) Insulin receptor internalization: molecular mechanisms and physiopathological implications. Diabetologia 37(Suppl 2):S117–S124PubMed
240.
Najjar SM (2002) Regulation of insulin action by CEACAM1. Trends Endocrinol Metab 13:240–245PubMed
241.
Najjar SM, Philippe N, Suzuki Y, Ignacio GA, Formisano P, Accili D, Taylor SI (1995) Insulin-stimulated phosphorylation of recombinant pp 120/HA4, an endogenous substrate of the insulin receptor tyrosine kinase. Biochemistry 34:9341–9349PubMed
242.
Li Calzi S, Choice CV, Najjar SM (1997) Differential effect of pp 120 on insulin endocytosis by two variant insulin receptor isoforms. Am J Physiol 273:E801–E808PubMed
243.
Formisano P, Najjar SM, Gross CN, Philippe N, Oriente F, Kern-Buell CL, Accili D, Gorden P (1995) Receptor-mediated internalization of insulin. Potential role of pp 120/HA4, a substrate of the insulin receptor kinase. J Biol Chem 270(41):24073–24077PubMed
244.
Najjar SM, Yang Y, Fernstrom MA, Lee SJ, Deangelis AM, Rjaily GA, Al-Share QY, Dai T, Miller TA, Ratnam S, Ruch RJ, Smith S, Lin SH, Beauchemin N, Oyarce AM (2005) Insulin acutely decreases hepatic fatty acid synthase activity. Cell Metab 2(1):43–53. doi:10.​1016/​j.​cmet.​2005.​06.​001 PubMed
245.
Matveyenko AV, Liuwantara D, Gurlo T, Kirakossian D, Dalla Man C, Cobelli C, White MF, Copps KD, Volpi E, Fujita S, Butler PC (2012) Pulsatile portal vein insulin delivery enhances hepatic insulin action and signaling. Diabetes 61(9):2269–2279. doi:10.​2337/​db11-1462 PubMed
246.
Ward GM, Walters JM, Aitken PM, Best JD, Alford FP (1990) Effects of prolonged pulsatile hyperinsulinemia in humans. Enhancement of insulin sensitivity. Diabetes Care 39(4):501–507
247.
Xu E, Dubois MJ, Leung N, Charbonneau A, Turbide C, Avramoglu RK, DeMarte L, Elchebly M, Streichert T, Levy E, Beauchemin N, Marette A (2009) Targeted disruption of carcinoembryonic antigen-related cell adhesion molecule 1 promotes diet-induced hepatic steatosis and insulin resistance. Endocrinology 150:3503–3512. doi:10.​1210/​en.​2008-1439 PubMed
248.
Park SY, Cho YR, Kim HJ, Hong EG, Higashimori T, Lee SJ, Goldberg IJ, Shulman GI, Najjar SM, Kim JK (2006) Mechanism of glucose intolerance in mice with dominant negative mutation of CEACAM1. Am J Physiol Endocrinol Metab 291(3):E517–E524. doi:10.​1152/​ajpendo.​00077.​2006 PubMed
249.
Lee SJ, Heinrich G, Fedorova L, Al-Share QY, Ledford KJ, Fernstrom MA, McInerney MF, Erickson SK, Gatto-Weis C, Najjar SM (2008) Development of nonalcoholic steatohepatitis in insulin-resistant liver-specific S503A carcinoembryonic antigen-related cell adhesion molecule 1 mutant mice. Gastroenterology 135(6):2084–2095. doi:10.​1053/​j.​gastro.​2008.​08.​007 PubMedPubMedCentral
250.
Ghosh S, Kaw M, Patel PR, Ledford KJ, Bowman TA, McLnerney MF, Erickson SK, Bourey RE, Najjar SM (2010) Mice with null mutation of Ceacam I develop nonalcoholic steatohepatitis. Hepat Med Res Evidence 2010(2):69–78. doi:10.​2147/​HMER.​S8902
251.
Najjar SM, Ledford KJ, Abdallah SL, Paus A, Russo L, Kaw MK, Ramakrishnan SK, Muturi HT, Raphael CK, Lester SG, Heinrich G, Pierre SV, Benndorf R, Kleff V, Jaffa AA, Levy E, Vazquez G, Goldberg IJ, Beauchemin N, Scalia R, Ergun S (2013) Ceacam1 deletion causes vascular alterations in large vessels. Am J Physiol Endocrinol Metab 305(4):E519–E529. doi:10.​1152/​ajpendo.​00266.​2013 PubMed
252.
Nagaishi T, Pao L, Lin SH, Iijima H, Kaser A, Qiao SW, Chen Z, Glickman J, Najjar SM, Nakajima A, Neel BG, Blumberg RS (2006) SHP1 phosphatase-dependent T cell inhibition by CEACAM1 adhesion molecule isoforms. Immunity 25:769–781PubMed
253.
Aarsland A, Chinkes D, Wolfe RR (1996) Contributions of de novo synthesis of fatty acids to total VLDL-triglyceride secretion during prolonged hyperglycemia/hyperinsulinemia in normal man. J Clin Invest 98:2008–2017PubMedPubMedCentral
254.
Angulo P, Keach JC, Batts KP, Lindor KD (1999) Independent predictors of liver fibrosis in patients with nonalcoholic steatohepatitis. Hepatology 30:1356–1362PubMed
255.
256.
Chiang SH, Bazuine M, Lumeng CN, Geletka LM, Mowers J, White NM, Ma JT, Zhou J, Qi N, Westcott D, Delproposto JB, Blackwell TS, Yull FE, Saltiel AR (2009) The protein kinase IKKepsilon regulates energy balance in obese mice. Cell 138(5):961–975. doi:10.​1016/​j.​cell.​2009.​06.​046 PubMedPubMedCentral
257.
Kim F, Pham M, Maloney E, Rizzo NO, Morton GJ, Wisse BE, Kirk EA, Chait A, Schwartz MW (2008) Vascular inflammation, insulin resistance, and reduced nitric oxide production precede the onset of peripheral insulin resistance. Arterioscler Thromb Vasc Biol 28:1982–1988. doi:10.​1161/​ATVBAHA.​108.​169722 PubMedPubMedCentral
258.
259.
Mari M, Caballero F, Colell A, Morales A, Caballeria J, Fernandez A, Enrich C, Fernandez-Checa JC, Garcia-Ruiz C (2006) Mitochondrial free cholesterol loading sensitizes to TNF- and Fas-mediated steatohepatitis. Cell Metab 4:185–198PubMed
260.
Canbay A, Higuchi H, Bronk SF, Taniai M, Sebo TJ, Gores GJ (2002) Fas enhances fibrogenesis in the bile duct ligated mouse: a link between apoptosis and fibrosis. Gastroenterology 123(4):1323–1330PubMed
261.
262.
Carter-Kent C, Zein NN, Feldstein AE (2008) Cytokines in the pathogenesis of fatty liver and disease progression to steatohepatitis: implications for treatment. Am J Gastroenterol 103:1036–1042PubMed
263.
Metadaten
Titel
CEACAM1 loss links inflammation to insulin resistance in obesity and non-alcoholic steatohepatitis (NASH)
verfasst von
Sonia M. Najjar
Lucia Russo
Publikationsdatum
01.01.2014
Verlag
Springer Berlin Heidelberg
Erschienen in
Seminars in Immunopathology / Ausgabe 1/2014
Print ISSN: 1863-2297
Elektronische ISSN: 1863-2300
DOI
https://doi.org/10.1007/s00281-013-0407-3

Weitere Artikel der Ausgabe 1/2014

Seminars in Immunopathology 1/2014 Zur Ausgabe

Introduction

Metabolic syndrome: variations on the theme of inflammation

Review

Functional crosstalk of PGC-1 coactivators and inflammation in skeletal muscle pathophysiology

Review

Immune cells and metabolic dysfunction

Review

Dendritic cells in atherosclerosis

Review

Gut microbiome and metabolic diseases

Review

Microbiota and nonalcoholic steatohepatitis

Leitlinien kompakt für die Innere Medizin

Mit medbee Pocketcards sicher entscheiden.

Seit 2022 gehört die medbee GmbH zum Springer Medizin Verlag

Kostenlos registrieren

Neu im Fachgebiet Innere Medizin

Echinokokkose medikamentös behandeln oder operieren?

06.05.2024 DCK 2024 Kongressbericht

Die Therapie von Echinokokkosen sollte immer in spezialisierten Zentren erfolgen. Eine symptomlose Echinokokkose kann – egal ob von Hunde- oder Fuchsbandwurm ausgelöst – konservativ erfolgen. Wenn eine Op. nötig ist, kann es sinnvoll sein, vorher Zysten zu leeren und zu desinfizieren. 

Umsetzung der POMGAT-Leitlinie läuft

03.05.2024 DCK 2024 Kongressbericht

Seit November 2023 gibt es evidenzbasierte Empfehlungen zum perioperativen Management bei gastrointestinalen Tumoren (POMGAT) auf S3-Niveau. Vieles wird schon entsprechend der Empfehlungen durchgeführt. Wo es im Alltag noch hapert, zeigt eine Umfrage in einem Klinikverbund.

Proximale Humerusfraktur: Auch 100-Jährige operieren?

01.05.2024 DCK 2024 Kongressbericht

Mit dem demographischen Wandel versorgt auch die Chirurgie immer mehr betagte Menschen. Von Entwicklungen wie Fast-Track können auch ältere Menschen profitieren und bei proximaler Humerusfraktur können selbst manche 100-Jährige noch sicher operiert werden.

Die „Zehn Gebote“ des Endokarditis-Managements

30.04.2024 Endokarditis Leitlinie kompakt

Worauf kommt es beim Management von Personen mit infektiöser Endokarditis an? Eine Kardiologin und ein Kardiologe fassen die zehn wichtigsten Punkte der neuen ESC-Leitlinie zusammen.

Update Innere Medizin

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.

Newsletter bestellen
Bildnachweise