Horm Metab Res 2008; 40(7): 467-472
DOI: 10.1055/s-2008-1065324
Animals, Clinical

© Georg Thieme Verlag KG Stuttgart · New York

Retinol-binding Protein 4 and Nicotinamide Phosphoribosyltransferase/Visfatin in Rat Obesity Models

J. Mercader 1 , N. Granados 1 , A. Caimari 1 , P. Oliver 1 , M. L. Bonet 1 , A. Palou 1
  • 1Laboratory of Molecular Biology, Nutrition and Biotechnology, Universitat de les Illes Balears, Palma de Mallorca, Spain and CIBER Fisiopatología de la Obesidad y Nutrición (CB06/03), Instituto de Salud Carlos III, Spain
Further Information

Publication History

received 18.07.2007

accepted 17.12.2007

Publication Date:
27 March 2008 (online)

Abstract

Retinol-binding protein 4 (RBP4) and nicotinamide phosphoribosyltransferase/visfatin (Nampt/visfatin) are adipocyte-secreted proteins (adipokines) whose relevance to the metabolic syndrome and regulation in obesity remain controversial. Here, we tested the hypothesis that adipose tissue expression and circulating levels of these two adipokines are elevated in obesity by analyzing their changes in both a genetic and a diet-induced model of obesity in the rat (obese fa/fa Zucker rats and Wistar rats fed a cafeteria diet, respectively). Compared with lean controls, obese fa/fa rats were hyperleptinemic, hyperinsulinemic, and insulin resistant and had reduced RBP4 serum levels and mRNA levels in adipose depots, unchanged Nampt/visfatin serum levels, and reduced Nampt/visfatin mRNA levels selectively in the inguinal adipose depot. Cafeteria diet-induced obesity resulted in increased fed blood glucose levels, a variable degree of insulin resistance, unchanged serum Nampt/visfatin and RBP4 levels, and reduced mRNA levels of both adipokines in several adipose depots. Hence, increases in RBP4 or Nampt/visfatin do not accompany obesity and insulin resistance in the models examined.

References

  • 1 Fischer-Posovszky P, Wabitsch M, Hochberg Z. Endocrinology of adipose tissue – an update.  Horm Metab Res. 2007;  39 314-321
  • 2 Yang Q, Graham TE, Mody N, Preitner F, Peroni OD, Zabolotny JM, Kotani K, Quadro L, Kahn BB. Serum retinol binding protein 4 contributes to insulin resistance in obesity and type 2 diabetes.  Nature. 2005;  436 356-362
  • 3 Fukuhara A, Matsuda M, Nishizawa M, Segawa K, Tanaka M, Kishimoto K, Matsuki Y, Murakami M, Ichisaka T, Murakami H, Watanabe E, Takagi T, Akiyoshi M, Ohtsubo T, Kihara S, Yamashita S, Makishima M, Funahashi T, Yamanaka S, Hiramatsu R, Matsuzawa Y, Shimomura I. Visfatin: a protein secreted by visceral fat that mimics the effects of insulin.  Science. 2005;  307 426-430 , . (Retraction in: Science 2007; 318: 565)
  • 4 Revollo JR, Korner A, Mills KF, Satoh A, Wang T, Garten A, Dasgupta B, Sasaki Y, Wolberger C, Townsend RR, Milbrandt J, Kiess W, Imai S. Nampt/PBEF/Visfatin regulates insulin secretion in beta cells as a systemic NAD biosynthetic enzyme.  Cell Metab. 2007;  6 363-375
  • 5 Kloting N, Kloting I. Visfatin: gene expression in isolated adipocytes and sequence analysis in obese WOKW rats compared with lean control rats.  Biochem Biophys Res Commun. 2005;  332 1070-1072
  • 6 Rodriguez AM, Quevedo-Coli S, Roca P, Palou A. Sex-dependent dietary obesity, induction of UCPs, and leptin expression in rat adipose tissues.  Obesity Res. 2001;  9 579-588
  • 7 Matthews DR, Hosker JP, Rudenski AS, Naylor BA, Treacher DF, Turner RC. Homeostasis model assessment: insulin resistance and beta-cell function from fasting plasma glucose and insulin concentrations in man.  Diabetologia. 1985;  28 412-419
  • 8 Gabrielsson BG, Olofsson LE, Sjogren A, Jernas M, Elander A, Lonn M, Rudemo M, Carlsson LM. Evaluation of reference genes for studies of gene expression in human adipose tissue.  Obesity Res. 2005;  13 649-652
  • 9 Livak KJ, Schmittgen TD. Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) Method.  Methods. 2001;  25 402-408
  • 10 Graham TE, Yang Q, Bluher M, Hammarstedt A, Ciaraldi TP, Henry RR, Wason CJ, Oberbach A, Jansson PA, Smith U, Kahn BB. Retinol-binding protein 4 and insulin resistance in lean, obese, and diabetic subjects.  N Engl J Med. 2006;  354 2552-2563
  • 11 Lee DC, Lee JW, Im JA. Association of serum retinol binding protein 4 and insulin resistance in apparently healthy adolescents.  Metabolism. 2007;  56 327-331
  • 12 Broch M, Vendrell J, Ricart W, Richart C, Fernandez-Real JM. Circulating retinol-binding protein-4, insulin sensitivity, insulin secretion, and insulin disposition index in obese and nonobese subjects.  Diabetes Care. 2007;  30 1802-1806
  • 13 Janke J, Engeli S, Boschmann M, Adams F, Bohnke J, Luft FC, Sharma AM, Jordan J. Retinol-binding protein 4 in human obesity.  Diabetes. 2006;  55 2805-2810
  • 14 Stefan N, Hennige AM, Staiger H, Machann J, Schick F, Schleicher E, Fritsche A, Haring HU. High circulating retinol-binding protein 4 is associated with elevated liver fat but not with total, subcutaneous, visceral, or intramyocellular fat in humans.  Diabetes Care. 2007;  30 1173-1178
  • 15 Gavi S, Stuart LM, Kelly P, Melendez MM, Mynarcik DC, Gelato MC, MacNurlan MA. Retinol-binding protein 4 is associated with insulin resistance and body fat distribution in nonobese subjects without type 2 diabetes.  J Clin Endocrinol Metab. 2007;  92 1886-1890
  • 16 Cho YM, Youn BS, Lee H, Lee N, Min SS, Kwak SH, Lee HK, Park KS. Plasma retinol-binding protein-4 concentrations are elevated in human subjects with impaired glucose tolerance and type 2 diabetes.  Diabetes Care. 2006;  29 2457-2461
  • 17 Silha JV, Nyomba BL, Leslie WD, Murphy LJ. Ethnicity, insulin resistance, and inflammatory adipokines in women at high and low risk for vascular disease.  Diabetes Care. 2007;  30 286-291
  • 18 Graham TE, Wason CJ, Bluher M, Kahn BB. Shortcomings in methodology complicate measurements of serum retinol binding protein (RBP4) in insulin-resistant human subjects.  Diabetologia. 2007;  50 814-823
  • 19 Ost A, Danielsson A, Liden M, Eriksson U, Nystrom FH, Stralfors P. Retinol-binding protein-4 attenuates insulin-induced phosphorylation of IRS1 and ERK1/2 in primary human adipocytes.  FASEB J. 2007;  21 3696-3704
  • 20 Veer E van der, Ho C, O’Neil C, Barbosa N, Scott R, Cregan SP, Pickering JG. Extension of human cell lifespan by nicotinamide phosphoribosyltransferase.  J Biol Chem. 2007;  282 10841-10845
  • 21 Segawa K, Fukuhara A, Hosogai N, Morita K, Okuno Y, Tanaka M, Nakagawa Y, Kihara S, Funahashi T, Komuro R, Matsuda M, Shimomura I. Visfatin in adipocytes is upregulated by hypoxia through HIF1alpha-dependent mechanism.  Biochem Biophys Res Commun. 2006;  349 875-882
  • 22 Bae SK, Kim SR, Kim JG, Kim JY, Koo TH, Jang HO, Yun I, Yoo MA, Bae MK. Hypoxic induction of human visfatin gene is directly mediated by hypoxia-inducible factor-1.  FEBS Lett. 2006;  580 4105-4113
  • 23 Kim SR, Bae SK, Choi KS, Park SY, Jun HO, Lee JY, Jang HO, Yun I, Yoon KH, Kim YJ, Yoo MA, Kim KW, Bae MK. Visfatin promotes angiogenesis by activation of extracellular signal-regulated kinase 1/2.  Biochem Biophys Res Commun. 2007;  357 150-156
  • 24 Jia SH, Li Y, Parodo J, Kapus A, Fan L, Rotstein OD, Marshall JC. Pre-B cell colony-enhancing factor inhibits neutrophil apoptosis in experimental inflammation and clinical sepsis.  J Clin Invest. 2004;  113 1318-1327
  • 25 Berndt J, Kloting N, Kralisch S, Kovacs P, Fasshauer M, Schon MR, Stumvoll M, Bluher M. Plasma visfatin concentrations and fat depot-specific mRNA expression in humans.  Diabetes. 2005;  54 2911-2916
  • 26 Haider DG, Holzer G, Schaller G, Weghuber D, Widhalm K, Wagner O, Kapiotis S, Wolzt M. The adipokine visfatin is markedly elevated in obese children.  J Pediatr Gastroenterol Nutr. 2006;  43 548-549
  • 27 Sandeep S, Velmurugan K, Deepa R, Mohan V. Serum visfatin in relation to visceral fat, obesity, and type 2 diabetes mellitus in Asian Indians.  Metabolism. 2007;  56 565-570
  • 28 Haider DG, Schindler K, Schaller G, Prager G, Wolzt M, Ludvik B. Increased plasma visfatin concentrations in morbidly obese subjects are reduced after gastric banding.  J Clin Endocrinol Metab. 2006;  91 1578-1581
  • 29 Pagano C, Pilon C, Olivieri M, Mason P, Fabris R, Serra R, Milan G, Rossato M, Federspil G, Vettor R. Reduced plasma visfatin/pre-B cell colony-enhancing factor in obesity is not related to insulin resistance in humans.  J Clin Endocrinol Metab. 2006;  91 3165-3170
  • 30 Jian WX, Luo TH, Gu YY, Zhang HL, Zheng S, Dai M, Han JF, Zhao Y, Li G, Luo M. The visfatin gene is associated with glucose and lipid metabolism in a Chinese population.  Diabet Med. 2006;  23 967-973
  • 31 Dogru T, Sonmez A, Tasci I, Bozoglu E, Yilmaz MI, Genc H, Erdem G, Gok M, Bingol N, Kilic S, Ozgurtas T, Bingol S. Plasma visfatin levels in patients with newly diagnosed and untreated type 2 diabetes mellitus and impaired glucose tolerance.  Diabetes Res Clin Pract. 2007;  76 24-29
  • 32 Wang P, Greevenbroek MM van, Bouwman FG, Brouwers MC, Kallen CJ van der, Smit E, Keijer J, Mariman EC. The circulating PBEF/NAMPT/visfatin level is associated with a beneficial blood lipid profile.  Pflugers Arch. 2007;  454 971-976
  • 33 Chen MP, Chung FM, Chang DM, Tsai JC, Huang HF, Shin SJ, Lee YJ. Elevated plasma level of visfatin/pre-B cell colony-enhancing factor in patients with type 2 diabetes mellitus.  J Clin Endocrinol Metab. 2006;  91 295-299
  • 34 Tsiotra PC, Tsigos C, Yfanti E, Anastasiou E, Vikentiou M, Psarra K, Papasteriades C, Raptis SA. Visfatin, TNF-alpha and IL-6 mRNA expression is increased in mononuclear cells from type 2 diabetic women.  Horm Metab Res. 2007;  39 758-763

Correspondence

Dr. M. L. Bonet

Laboratori de Biologia Molecular

Nutrició i Biotecnologia

Departament de Biologia Fonamental i Ciències de la Salut

Universitat de les Illes Balears

Crta. Valldemossa Km 7.5

07122 Palma de Mallorca

Spain

Phone: +34/971/17 27 34

Fax: +34/971/17 34 26

Email: luisabonet@uib.es

    >