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Anatomical Science International

Erschienen in:

01.03.2018 | Review Article

Oncostatin M in the development of metabolic syndrome and its potential as a novel therapeutic target

verfasst von: Tadasuke Komori, Yoshihiro Morikawa

Erschienen in: Anatomical Science International | Ausgabe 2/2018

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Abstract

Oncostatin M (OSM), a member of the IL-6 family of cytokines, plays an important role in various biologic actions, including cell growth, neuronal development, and inflammatory responses. Recently, we demonstrated the unique relationship between OSM and metabolic syndrome in mice. Mice lacking OSM receptor β subunit (OSMRβ^−/− mice) exhibited late-onset obesity. Before the onset of obesity, adipose tissue inflammation and insulin resistance were observed in OSMRβ^−/− mice. In addition, high-fat diet-induced metabolic disorders, including obesity, adipose tissue inflammation, insulin resistance, and hepatic steatosis, were aggravated in OSMRβ^−/− mice compared to those in wild-type mice. Consistent with these findings, OSM treatment dramatically improved these metabolic disorders in the mouse model of metabolic syndrome. Interestingly, OSM directly changed the phenotypes of adipose tissue macrophages toward anti-inflammatory M2 type. Furthermore, fatty acid content in the hepatocytes was decreased by OSM through expression regulation of several key enzymes of hepatic lipid metabolism. These findings suggest that OSM is a novel therapeutic target for metabolic syndrome.

Abbott CR, Monteiro M, Small CJ et al (2005) The inhibitory effects of peripheral administration of peptide YY₃₋₃₆ and glucagon-like peptide-1 on food intake are attenuated by ablation of the vagal-brainstem-hypothalamic pathway. Brain Res 1044:127–131CrossRefPubMed

Berg AH, Scherer PE (2005) Adipose tissue inflammation and cardiovascular disease. Circ Res 96:939–949CrossRefPubMed

Bray GA, Bellanger T (2006) Epidemiology, trends, and morbidities of obesity and the metabolic syndrome. Endocrine 29:109–117CrossRefPubMed

Buettner R, Schölmerich J, Bollheimer LC (2007) High-fat diets: modeling the metabolic disorders of human obesity in rodents. Obesity (Silver Spring) 15:798–808CrossRef

Cawston TE, Curry VA, Summers CA et al (1998) The role of oncostatin M in animal and human connective tissue collagen turnover and its localization within the rheumatoid joint. Arthritis Rheum 41:1760–1771CrossRefPubMed

de Hooge AS, van de Loo FA, Bennink MB et al (2003) Growth plate damage, a feature of juvenile idiopathic arthritis, can be induced by adenoviral gene transfer of oncostatin M: a comparative study in gene-deficient mice. Arthritis Rheum 48:1750–1761CrossRefPubMed

Douglas AM, Grant SL, Goss GA, Clouston DR, Sutherland RL, Begley CG (1998) Oncostatin M induces the differentiation of breast cancer cells. Int J Cancer 75:64–73CrossRefPubMed

Eckel R (2015) The Metabolic Syndrome. In: Kasper DL, Fauci AS, Hauser SL, Longo DL, Jameson JL, Loscaldo J (eds) Harrison’s principles of internal medicine. Mc Graw Hill Education, New York, pp 2449–2454

Elks CM, Zhao P, Grant RW et al (2016) Loss of oncostatin M signaling in adipocytes induces insulin resistance and adipose tissue inflammation in vivo. J Biol Chem 291:17066–17076CrossRefPubMedPubMedCentral

Feng B, Jiao P, Nie Y et al (2011) Clodronate liposomes improve metabolic profile and reduce visceral adipose macrophage content in diet-induced obese mice. PLoS One 6:e24358CrossRefPubMedPubMedCentral

Fujisaka S, Usui I, Bukhari A et al (2009) Regulatory mechanisms for adipose tissue M1 and M2 macrophages in diet-induced obese mice. Diabetes 58:2574–2582CrossRefPubMedPubMedCentral

Garbers C, Hermanns HM, Schaper F et al (2012) Plasticity and cross-talk of interleukin 6-type cytokines. Cytokine Growth Factor Rev 23:85–97CrossRefPubMed

Gearing DP, Bruce AG (1992) Oncostatin M binds the high-affinity leukemia inhibitory factor receptor. New Biol 4:61–65PubMed

Gordon S (2003) Alternative activation of macrophages. Nat Rev Immunol 3:23–35CrossRefPubMed

Grenier A, Dehoux M, Boutten A et al (1999) Oncostatin M production and regulation by human polymorphonuclear neutrophils. Blood 93:1413–1421PubMed

Grove RI, Mazzucco CE, Radka SF, Shoyab M, Kiener PA (1991) Oncostatin M up-regulates low density lipoprotein receptors in HepG2 cells by a novel mechanism. J Biol Chem 266:18194–18199PubMed

Halfter H, Lotfi R, Westermann R, Young P, Ringelstein EB, Stögbauer FT (1998) Inhibition of growth and induction of differentiation of glioma cell lines by oncostatin M (OSM). Growth Factors 15:135–147CrossRefPubMed

Hamilton TA (2002) Molecular basis of macrophage activation: from gene expression to phenotypiv diversity. In: Bourke B, Lewis C (eds) The Macrophage. Oxford University Press, Oxford, pp 73–102

Henkel J, Gartner D, Dorn C et al (2011) Oncostatin M produced in kupffer cells in response to pge2: possible contributor to hepatic insulin resistance and steatosis. Lab Invest 91:1107–1117CrossRefPubMed

Hotamisligil GS (2006) Inflammation and metabolic disorders. Nature 444:860–867CrossRefPubMed

Ichihara M, Hara T, Kim H, Murate T, Miyajima A (1997) Oncostatin M and leukemia inhibitory factor do not use the same functional receptor in mice. Blood 90:165–173PubMed

Kamiya A, Kinoshita T, Ito Y et al (1999) Fetal liver development requires a paracrine action of oncostatin M through the gp130 signal transducer. EMBO J 18:2127–2136CrossRefPubMedPubMedCentral

Kanda H, Tateya S, Tamori Y et al (2006) MCP-1 contributes to macrophage infiltration into adipose tissue, insulin resistance, and hepatic steatosis in obesity. J Clin Invest 116:1494–1505CrossRefPubMedPubMedCentral

Komori T, Tanaka M, Senba E, Miyajima A, Morikawa Y (2013) Lack of oncostatin M receptor β leads to adipose tissue inflammation and insulin resistance by switching macrophage phenotype. J Biol Chem 288:21861–21875CrossRefPubMedPubMedCentral

Komori T, Tanaka M, Senba E, Miyajima A, Morikawa Y (2014) Deficiency of oncostatin M receptor β (OSMRβ) exacerbates high-fat diet-induced obesity and related metabolic disorders in mice. J Biol Chem 289:13821–13837CrossRefPubMedPubMedCentral

Komori T, Tanaka M, Furuta H, Akamizu T, Miyajima A, Morikawa Y (2015) Oncostatin M is a potential agent for the treatment of obesity and related metabolic disorders: a study in mice. Diabetologia 58:1868–1876CrossRefPubMed

Lindberg RA, Juan TS, Welcher AA et al (1998) Cloning and characterization of a specific receptor for mouse oncostatin M. Mol Cell Biol 18:3357–3367CrossRefPubMedPubMedCentral

Loy JK, Davidson TJ, Berry KK, Macmaster JF, Danle B, Durham SK (1999) Oncostatin M: development of a pleiotropic cytokine. Toxicol Pathol 27:151–155CrossRefPubMed

Lumeng CN, Bodzin JL, Saltiel AR (2007) Obesity induces a phenotypic switch in adipose tissue macrophage polarization. J Clin Invest 117:175–184CrossRefPubMedPubMedCentral

Lumeng CN, DelProposto JB, Westcott DJ, Saltiel AR (2008) Phenotypic switching of adipose tissue macrophages with obesity is generated by spatiotemporal differences in macrophage subtypes. Diabetes 57:3239–3246CrossRefPubMedPubMedCentral

Luo P, Wang PX, Li ZZ et al (2016) Hepatic oncostatin M receptor β regulates obesity-induced steatosis and insulin resistance. Am J Pathol 186:1278–1292CrossRefPubMed

Luzina IG, Atamas SP, Wise R et al (2003) Occurrence of an activated, profibrotic pattern of gene expression in lung CD8 + T cells from scleroderma patients. Arthritis Rheum 48:2262–2274CrossRefPubMed

Mandal P, Pratt BT, Barnes M, McMullen MR, Nagy LE (2011) Molecular mechanism for adiponectin-dependent M2 macrophage polarization: link between the metabolic and innate immune activity of full-length adiponectin. J Biol Chem 286:13460–13469CrossRefPubMedPubMedCentral

Miyajima A, Kinoshita T, Tanaka M, Kamiya A, Mukouyama Y, Hara T (2000) Role of oncostatin M in hematopoiesis and liver development. Cytokine Growth Factor Rev 11:177–183CrossRefPubMed

Miyaoka Y, Tanaka M, Naiki T, Miyajima A (2006) Oncostatin M inhibits adipogenesis through the ras/erk and STAT5 signaling pathways. J Biol Chem 281:37913–37920CrossRefPubMed

Modur V, Feldhaus MJ, Weyrich AS et al (1997) Oncostatin M is a proinflammatory mediator. In vivo effects correlate with endothelial cell expression of inflammatory cytokines and adhesion molecules. J Clin Invest 100:158–168CrossRefPubMedPubMedCentral

Morikawa Y (2005) Oncostatin M in the development of the nervous system. Anat Sci Int 80:53–59CrossRefPubMed

Morikawa Y, Tamura S, Minehata K, Donovan PJ, Miyajima A, Senba E (2004) Essential function of oncostatin m in nociceptive neurons of dorsal root ganglia. J Neurosci 24:1941–1947CrossRefPubMed

Mosley B, De Imus C, Friend D et al (1996) Dual oncostatin M (OSM) receptors. Cloning and characterization of an alternative signaling subunit conferring OSM-specific receptor activation. J Biol Chem 271:32635–33243CrossRefPubMed

Mozaffarian A, Brewer AW, Trueblood ES et al (2008) Mechanisms of oncostatin M-induced pulmonary inflammation and fibrosis. J Immunol 181:7243–7253CrossRefPubMed

Müller MJ, Geisler C (2017) From the past to future: from energy expenditure to energy intake to energy expenditure. Eur J Clin Nutr 71:358–364CrossRefPubMed

Nair BC, DeVico AL, Nakamura S et al (1992) Identification of a major growth factor for AIDS-Kaposi’s sarcoma cells as oncostatin M. Science 255:1430–1432CrossRefPubMed

Nakamura K, Nonaka H, Saito H, Tanaka M, Miyajima A (2004) Hepatocyte proliferation and tissue remodeling is impaired after liver injury in oncostatin M receptor knockout mice. Hepatology 39:635–644CrossRefPubMed

Nishimura S, Manabe I, Nagasaki M et al (2009) CD8 effector T cells contribute to macrophage recruitment and adipose tissue inflammation in obesity. Nat Med 15:914–920CrossRefPubMed

Okaya A, Kitanaka J, Kitanaka N et al (2005) Oncostatin M inhibits proliferation of rat oval cells, OC15-5, inducing differentiation into hepatocytes. Am J Pathol 166:709–719CrossRefPubMedPubMedCentral

Pohin M, Guesdon W, Mekouo AA et al (2016) Oncostatin M overexpression induces skin inflammation but is not required in the mouse model of imiquimod-induced psoriasis-like inflammation. Eur J Immunol 46:1737–1751CrossRefPubMed

Poirier P, Giles TD, Bray GA et al (2006) American Heart Association; Obesity Committee of the Council on Nutrition, Physical Activity, Metabolism, Obesity, and Cardiovascular Disease: pathophysiology, evaluation, and effect of weight loss: an update of the 1997 American Heart Association Scientific Statement on Obesity and Heart Disease from the Obesity Committee of the Council on Nutrition, Physical Activity, and Metabolism. Circulation 113:898–918CrossRefPubMed

Rocha VZ, Libby P (2009) Obesity, inflammation, and atherosclerosis. Nat Rev Cardiol 6:399–409CrossRefPubMed

Rose TM, Bruce AG (1991) Oncostatin M is a member of a cytokine family that includes leukemia-inhibitory factor, granulocyte colony-stimulating factor, and interleukin 6. Proc Natl Acad Sci USA 88:8641–8645CrossRefPubMedPubMedCentral

Sánchez-Infantes D, White UA, Elks CM et al (2014) Oncostatin m is produced in adipose tissue and is regulated in conditions of obesity and type 2 diabetes. J Clin Endocrinol Metab 99:E217–E225CrossRefPubMed

Sánchez-Infantes D, Cereijo R, Peyrou M, Piquer-Garcia I, Stephens JM, Villarroya F (2017) Oncostatin m impairs brown adipose tissue thermogenic function and the browning of subcutaneous white adipose tissue. Obesity (Silver Spring) 25:85–93CrossRef

Schenk S, Saberi M, Olefsky JM (2008) Insulin sensitivity: modulation by nutrients and inflammation. J Clin Invest 118:2992–3002CrossRefPubMedPubMedCentral

Sica A, Mantovani A (2012) Macrophage plasticity and polarization: in vivo veritas. J Clin Invest 122:787–795CrossRefPubMedPubMedCentral

Taga T, Kishimoto T (1997) Gp130 and the interleukin-6 family of cytokines. Annu Rev Immunol 15:797–819CrossRefPubMed

Talsania T, Anini Y, Siu S, Drucker DJ, Brubaker PL (2005) Peripheral exendin-4 and peptide YY3-36 synergistically reduce food intake through different mechanisms in mice. Endocrinology 146:3748–3756CrossRefPubMed

Talukdar S, da Oh Y, Bandyopadhyay G et al (2012) Neutrophils mediate insulin resistance in mice fed a high-fat diet through secreted elastase. Nat Med 18:1407–1412CrossRefPubMedPubMedCentral

Tamura S, Morikawa Y, Miyajima A, Senba E (2002) Expression of oncostatin M in hematopoietic organs. Dev Dyn 225:327–331CrossRefPubMed

Tamura S, Morikawa Y, Miyajima A, Senba E (2003) Expression of oncostatin M receptor beta in a specific subset of nociceptive sensory neurons. Eur J Neurosci 17:2287–2298CrossRefPubMed

Tanaka M, Hara T, Copeland NG, Gilbert DJ, Jenkins NA, Miyajima A (1999) Reconstitution of the functional mouse oncostatin M (OSM) receptor: molecular cloning of the mouse OSM receptor beta subunit. Blood 93:804–815PubMed

Thoma B, Bird TA, Friend DJ, Gearing DP, Dower SK (1994) Oncostatin M and leukemia inhibitory factor trigger overlapping and different signals through partially shared receptor complexes. J Biol Chem 269:6215–6222PubMed

Walker EC, McGregor NE, Poulton IJ et al (2010) Oncostatin M promotes bone formation independently of resorption when signaling through leukemia inhibitory factor receptor in mice. J Clin Invest 120:582–592CrossRefPubMedPubMedCentral

Wallace PM, MacMaster JF, Rouleau KA et al (1999) Regulation of inflammatory responses by oncostatin M. J Immunol 162:5547–5555PubMed

Weisberg SP, McCann D, Desai M, Rosenbaum M, Leibel RL, Ferrante AW Jr (2003) Obesity is associated with macrophage accumulation in adipose tissue. J Clin Invest 112:1796–1808CrossRefPubMedPubMedCentral

Wu D, Molofsky AB, Liang HE et al (2011) Eosinophils sustain adipose alternatively activated macrophages associated with glucose homeostasis. Science 332:243–247CrossRefPubMedPubMedCentral

Yoshimura A, Ichihara M, Kinjyo I et al (1996) Mouse oncostatin M: an immediate early gene induced by multiple cytokines through the JAK-STAT5 pathway. EMBO J 15:1055–1063PubMedPubMedCentral

Zarling JM, Shoyab M, Marquardt H, Hanson MB, Lioubin MN, Todaro GJ (1986) Oncostatin M: a growth regulator produced by differentiated histiocytic lymphoma cells. Proc Natl Acad Sci USA 83:9739–9743CrossRefPubMedPubMedCentral

Zhou Y, Abidi P, Kim A et al (2007) Transcriptional activation of hepatic ACSL3 and ACSL5 by oncostatin m reduces hypertriglyceridemia through enhanced beta-oxidation. Arterioscler Thromb Vasc Biol 27:2198–2205CrossRefPubMed

Titel: Oncostatin M in the development of metabolic syndrome and its potential as a novel therapeutic target
verfasst von: Tadasuke Komori
Yoshihiro Morikawa
Publikationsdatum: 01.03.2018
Verlag: Springer Singapore
Erschienen in: Anatomical Science International / Ausgabe 2/2018
Print ISSN: 1447-6959
Elektronische ISSN: 1447-073X
DOI: https://doi.org/10.1007/s12565-017-0421-y

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