Influence of membrane-bound tumor necrosis factor (TNF)-alpha on obesity and glucose metabolism

[en] OBJECTIVES: To investigate the influence of transmembrane tumor necrosis factor (TNF)-alpha on adipose tissue development and insulin-mediated glucose metabolism. METHODS AND RESULTS: TNF-alpha and lymphotoxin-alpha-deficient mice expressing non-cleavable transmembrane TNF-alpha (Tg-tmTNF-alpha) and TNF-alpha/lymphotoxin-alpha double knockout (control) mice were kept on high-fat diet for 15 weeks. The food intake and feeding efficiency of Tg-tmTNF-alpha mice were significantly higher compared with control mice. At the end of the study, Tg-tmTNF-alpha mice had a significantly higher total body weight, as well as subcutaneous and gonadal adipose tissue mass. Histological analysis revealed that the expression of Tg-tmTNF-alpha resulted in a significantly increased adipocyte area and blood vessel density. Plasma leptin levels correlated positively with adipose tissue mass. The plasma levels of total cholesterol and HDL-cholesterol were significantly increased and LDL-cholesterol levels significantly decreased in Tg-tmTNF-alpha mice. Fasting blood glucose and plasma insulin levels were not different between the two genotypes and intraperitoneal glucose and insulin tolerance tests did not show significant differences. CONCLUSIONS: Transmembrane TNF-alpha enhances adipose tissue formation without altering insulin-mediated glucose metabolism in mice with nutritionally induced obesity.

Disciplines :

Anatomy (cytology, histology, embryology...) & physiology

Author, co-author :

Vörös, Gabor

Maquoi, Erik ; Université de Liège - ULiège > Département des sciences cliniques > Labo de biologie des tumeurs et du développement

Collen, Désiré

Lijnen, Roger

Language :

English

Title :

Influence of membrane-bound tumor necrosis factor (TNF)-alpha on obesity and glucose metabolism

Publication date :

March 2004

Journal title :

Journal of Thrombosis and Haemostasis

ISSN :

1538-7933

eISSN :

1538-7836

Publisher :

Blackwell, United Kingdom

Volume :

Issue :

Pages :

507-513

Peer reviewed :

Peer Reviewed verified by ORBi

Available on ORBi :

since 12 February 2010

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Bibliography

Kelner, K., Helmuth, L., Obesity - What is to be done? (2003) Science, 299, pp. 845-849
Flegal, K.M., Carroll, M.D., Kuczmarski, R.J., Johnson, C.L., Overweight and obesity in the United States: Prevalence and trends, 1960-1994 (1998) Int. J. Obes. Relat. Metab. Disord., 22, pp. 39-47
Hotamisligil, G.S., Shargill, N.S., Spiegelman, B.M., Adipose expression of tumor necrosis factor-alpha: Direct role in obesity-linked insulin resistance (1993) Science, 259, pp. 87-91
Hotamisligil, G.S., Amer, P., Caro, J.F., Atkinson, R.L., Spiegelman, B.M., Increased adipose tissue expression of tumor necrosis factor-alpha in human obesity and insulin resistance (1995) J. Clin. Invest., 95, pp. 2409-2415
Uysal, K.T., Wiesbrock, S.M., Marino, M.W., Hotamisligil, G.S., Protection from obesity-induced insulin resistance in mice lacking TNF-alpha function (1997) Nature, 389, pp. 610-614
Ventre, J., Doebber, T., Wu, M., MacNaul, K., Stevens, K., Pasparakis, M., Kollias, G., Moller, D.E., Targeted disruption of the tumor necrosis factor-alpha gene: Metabolic consequences in obese and nonobese mice (1997) Diabetes, 46, pp. 1526-1531
Lijnen, H.R., Maquoi, E., Morange, P., Voros, G., Van Hoef, B., Kopp, F., Collen, D., Alessi, M.-C., Nutritionally induced obesity is attenuated in transgenic mice overexpressing plasminogen activator inhibitor-1 (2003) Arterioscler. Thromb. Vasc. Biol., 23, pp. 78-84
Kirchgessner, T.G., Uysal, K.T., Wiesbrock, S.M., Marino, M.W., Hotamisligil, G.S., Tumor necrosis factor-alpha contributes to obesity-related hyperleptinemia by regulating leptin release from adipocytes (1997) J. Clin. Invest., 100, pp. 2777-2782
Voros, G., Maquoi, E., Collen, D., Lijnen, H.R., Differential expression of plasminogen activator inhibitor-1, tumor necrosis factor-alpha, TNF-alpha converting enzyme and ADAMTS family members in murine fat territories (2003) Biochim. Biophys. Acta, 1625, pp. 36-42
Xu, H., Uysal, K.T., Becherer, J.D., Amer, P., Hotamisligil, G.S., Altered tumor necrosis factor-alpha (TNF-alpha) processing in adipocytes and increased expression of transmembrane TNF-alpha in obesity (2002) Diabetes, 51, pp. 1876-1883
Morimoto, Y., Nishikawa, K., Ohashi, M., KB-R7785, a novel matrix metalloproteinase inhibitor, exerts its antidiabetic effect by inhibiting tumor necrosis factor-alpha production (1997) Life Sci., 61, pp. 795-803
Togashi, N., Ura, N., Higashiura, K., Murakami, H., Shimamoto, K., Effect of TNF-alpha-converting enzyme inhibitor on insulin resistance in fructose-fed rats (2002) Hypertension, 39, pp. 578-580
Mueller, C., Corazza, N., Trachsel-Loseth, S., Eugster, H.P., Buhler-Jungo, M., Brunner, T., Imboden, M.A., Non-cleavable transmembrane mouse tumor necrosis factor-alpha (TNFalpha) mediates effects distinct from those of wild-type TNFalpha in vitro and in vivo (1999) J. Biol. Chem., 274, pp. 38112-38118
Lijnen, H.R., Maquoi, E., Demeulemeester, D., Van Hoef, B., Collen, D., Modulation of fibrinolytic and gelatinolytic activity during adipose tissue development in a mouse model of nutritionally induced obesity (2002) Thromb. Haemost., 88, pp. 345-353
Lijnen, H.R., Demeulemeester, D., Van Hoef, B., Collen, D., Maquoi, E., Deficiency of tissue inhibitor of matrix metalloproteinase-1 (TIMP-1) impairs nutritionally induced obesity in mice (2003) Thromb. Haemost., 89, pp. 249-255
Giles, A.R., Guidelines for the use of animals in biomedical research (1987) Thromb. Haemost., 58, pp. 1078-1084
Declerck, P.J., Verstreken, M., Collen, D., Immunoassay of murine t-PA, u-PA and PAI-1 using monoclonal antibodies raised in gene-inactivated mice (1995) Thromb. Haemost., 74, pp. 1305-1309
Folch, J., Lees, M., Sloane-Stanely, G.H., A simple method for the isolation and purification of total lipids from animal tissue (1957) J. Biol. Chem., 226, pp. 497-509
Maquoi, E., Munaut, C., Colige, A., Collen, D., Lijnen, H.R., Modulation of adipose tissue expression of murine matrix metalloproteinases and their tissue inhibitors with obesity (2002) Diabetes, 51, pp. 1093-1101
Rogers, P., Webb, G.P., Estimation of body fat in normal and obese mice (1980) Br. J. Nutr., 43, pp. 83-86
Xu, H., Sethi, J.K., Hotamisligil, G.S., Transmembrane tumor necrosis factor (TNF)-alpha inhibits adipocyte differentiation by selectively activating TNF receptor 1 (1999) J. Biol. Chem., 274, pp. 26287-26295
Pennica, D., Nedwin, G.E., Hayflick, J.S., Seeburg, P.H., Derynck, R., Palladino, M.A., Kohr, W.J., Goeddel, D.V., Human tumour necrosis factor: Precursor structure, expression and homology to lymphotoxin (1984) Nature, 312, pp. 724-729
Browning, J.L., Ngam-Ek, A., Lawton, P., DeMarinis, J., Tizard, R., Chow, E.P., Hession, C., Ware, C.F., Lymphotoxin beta, a novel member of the TNF family that forms a heteromeric complex with lymphotoxin on the cell surface (1993) Cell, 72, pp. 847-856
Crowe, P.D., VanArsdale, T.L., Walter, B.N., Ware, C.F., Hession, C., Ehrenfels, B., Browning, J.L., Smith, C.A., A lymphotoxin-beta-specific receptor (1994) Science, 264, pp. 707-710
De Togni, P., Goellner, J., Ruddle, N.H., Streeter, P.R., Fick, A., Mariathasan, S., Smith, S.C., Strauss-Schoenberger, J., Abnormal development of peripheral lymphoid organs in mice deficient in lymphotoxin (1994) Science, 264, pp. 703-707
Xu, H., Hirosumi, J., Uysal, K.T., Guler, A.D., Hotamisligil, G.S., Exclusive action of transmembrane TNF alpha in adipose tissue leads to reduced adipose mass and local but not systemic insulin resistance (2002) Endocrinology, 143, pp. 1502-1511
Yoneda, T., Alsina, M.A., Chavez, J.B., Bonewald, L., Nishimura, R., Mundy, G.R., Evidence that tumor necrosis factor plays a pathogenetic role in the paraneoplastic syndromes of cachexia, hypercalcemia, and leukocytosis in a human tumor in nude mice (1991) J. Clin. Invest., 87, pp. 977-985
Kawakami, M., Watanabe, N., Ogawa, H., Kato, A., Sando, H., Yamada, N., Murase, T., Oda, T., Cachectin/TNF kills or inhibits the differentiation of 3T3-L1 cells according to developmental stage (1989) J. Cell Physiol., 138, pp. 1-7
Ron, D., Brasier, A.R., McGehee Jr., R.E., Habener, J.F., Tumor necrosis factor-induced reversal of adipocytic phenotype of 3T3-L1 cells is preceded by a loss of nuclear CCAAT/enhancer binding protein (C/EBP) (1992) J. Clin. Invest., 89, pp. 223-233
Schreyer, S.A., Chua Jr., S.C., LeBoeuf, R.C., Obesity and diabetes in TNF-alpha receptor-deficient mice (1998) J. Clin. Invest., 102, pp. 402-411
Breder, C.D., Hazuka, C., Ghayur, T., Klug, C., Huginin, M., Yasuda, K., Teng, M., Saper, C.B., Regional induction of tumor necrosis factor alpha expression in the mouse brain after systemic lipopolysaccharide administration (1994) Proc. Natl. Acad. Sci. USA, 91, pp. 11393-11397
Plata-Salaman, C.R., Immunomodulators and feeding regulation: A humoral link between the immune and nervous systems (1989) Brain Behav. Immun., 3, pp. 193-213
Fantino, M., Wieteska, L., Evidence for a direct central anorectic effect of tumor-necrosis-factor-alpha in the rat (1993) Physiol. Behav., 53, pp. 477-483
Kapas, L., Krueger, J.M., Tumor necrosis factor-beta induces sleep, fever, and anorexia (1992) Am. J. Physiol., 263, pp. R703-R707
Feingold, K.R., Soued, M., Staprans, I., Gavin, L.A., Donahue, M.E., Huang, B.J., Moser, A.H., Grunfeld, C., Effect of tumor necrosis factor (TNF) on lipid metabolism in the diabetic rat. Evidence that inhibition of adipose tissue lipoprotein lipase activity is not required for TNF-induced hyperlipidemia (1989) J. Clin. Invest., 83, pp. 1116-1121
Cabana, V.G., Siegel, J.N., Sabesin, S.M., Effects of the acute phase response on the concentration and density distribution of plasma lipids and apolipoproteins (1989) J. Lipid Res., 30, pp. 39-49
Ly, H., Francone, O.L., Fielding, C.J., Shigenaga, J.K., Moser, A.H., Grunfeld, C., Feingold, K.R., Endotoxin and TNF lead to reduced plasma LCAT activity and decreased hepatic LCAT mRNA levels in Syrian hamsters (1995) J. Lipid Res., 36, pp. 1254-1263