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Horm Metab Res 2012; 44(01): 6-14
DOI: 10.1055/s-0031-1295491
Review
© Georg Thieme Verlag KG Stuttgart · New York

The Metabolic Role of Retinol Binding Protein 4: An Update

G. A. Christou
1   Laboratory of Physiology, Medical School, University of Ioannina, Ioannina, Greece
,
A. D. Tselepis
2   Laboratory of Biochemistry, Department of Chemistry, University of Ioannina, Ioannina, Greece
,
D. N. Kiortsis
1   Laboratory of Physiology, Medical School, University of Ioannina, Ioannina, Greece
› Author Affiliations
Further Information

Publication History

received 25 August 2011

accepted 02 November 2011

Publication Date:
28 December 2011 (online)

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Abstract

Retinol binding protein 4 (RBP4) is regarded as a novel cardiometabolic risk factor, which is secreted mainly by the hepatocytes and also by the adipose tissue. RBP4 has been shown to induce insulin resistance, and plasma RBP4 values are increased in type 2 diabetes mellitus, obesity, metabolic syndrome, and cardiovascular disease. Moreover, it has been found that circulating RBP4 decreases during medical interventions that result in amelioration of the metabolic profile, such as diet, exercise, oral antidiabetic drugs, and hypolipidemic agents. However, only few of the RBP4-related studies have investigated whether RBP4 constitutes a causal factor of the above-mentioned metabolic conditions. Importantly, circulating RBP4 is influenced by some nonmetabolic conditions, such as renal failure, acute illness, injury, and liver failure. Thus, further studies investigating the metabolic roles of RBP4 should be carefully planned, taking into account the effects of nonmetabolic conditions on circulating RBP4.

Key words

insulin resistance - lipid metabolism - adipose tissue - metabolic syndrome - adipokines - atherosclerosis
 

  • References

  • 1 Blaner WS. Retinol-binding protein: the serum transport protein for vitamin A. Endocr Rev 1989; 10: 308-316
    CrossrefPubMedGoogle Scholar
  • 2 Tsutsumi C, Okuno M, Tannous L, Piantedosi R, Allan M, Goodman DS, Blaner WS. Retinoids and retinoid-binding protein expression in rat adipocytes. J Biol Chem 1992; 267: 1805-1810
    PubMedGoogle Scholar
  • 3 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
    CrossrefPubMedGoogle Scholar
  • 4 Cabre A, Lazaro I, Girona J, Manzanares AF, Plana N, Heras M, Masana L. Retinol-binding protein 4 as a plasma biomarker of renal dysfunction and cardiovascular disease. J Intern Med 2007; 262: 496-503
    CrossrefPubMedGoogle Scholar
  • 5 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
    CrossrefPubMedGoogle Scholar
  • 6 Graham TE, Yang Q, Bluher M, Hammarstedt A, Ciaraldi TP, Henry RR, Wason CJ, Oberbach A, Jansson P, 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
    CrossrefPubMedGoogle Scholar
  • 7 Kloting N, Graham TE, Berndt J, Kralisch S, Kovacs P, Wason CJ, Fasshauer M, Schon MR, Stumvoll M, Bluher M, Kahn BB. Serum Retinol-Binding Protein is more highly expressed in visceral than in subcutaneous adipose tissue and is a marker of intra-abdominal fat mass. Cell Metab 2007; 6: 79-87
    CrossrefPubMedGoogle Scholar
  • 8 Kemp SF, Frindik JP. Effect of metabolic control on serum protein concentrations in diabetes. Acta Paediatr Scand 1991; 80: 938-943
    CrossrefPubMedGoogle Scholar
  • 9 Basu TK, Tze WJ, Leichter J. Serum vitamin A and retinol-binding protein in patients with insulin-dependent diabetes mellitus. Am J Clin Nutr 1989; 50: 329-331
    PubMedGoogle Scholar
  • 10 Jourdan M, Jaleel A, Karakelides H, Ford GC, Kahn BB, Nair KS. Impact of type 1 diabetes and insulin treatment on plasma levels and fractional synthesis rate of retinol-binding protein 4. J Clin Endocrinol Metab 2009; 94: 5125-5130
    CrossrefPubMedGoogle Scholar
  • 11 Krill D, OLeary L, Koehler AN, Kramer MK, Warty V, Wagner MA, Dorman JS. Association of retinol binding protein in multiple-case families with insulin-dependent diabetes. Hum Biol 1997; 69: 89-96
    PubMedGoogle Scholar
  • 12 Chan TF, Chen HS, Chen YC, Lee CH, Chou FH, Chen IJ, Chen SY, Jong SB, Tsai EM. Increased serum retinol-binding protein 4 concentrations in women with gestational diabetes mellitus. Reprod Sci 2007; 14: 169-174
    CrossrefPubMedGoogle Scholar
  • 13 Su Y, Hong J, Yan Q, Xu C, Gu W, Zhang Y, Shen C, Chi Z, Dai M, Xu M, Zhang Y, Liu Q, Wang WQ, Li XY, Ning G. Increased serum retinol-binding protein-4 levels in pregnant women with and without gestational diabetes mellitus. Diabetes Metab 2010; 36: 470-475
    CrossrefPubMedGoogle Scholar
  • 14 Stefan N, Hennige AM, Staiger H, Machann J, Shick 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
    CrossrefPubMedGoogle Scholar
  • 15 Gavi S, Stuart LM, Kelly P, Melendez MM, Mynarcik DC, Gelato MS, McNurlan 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
    CrossrefPubMedGoogle Scholar
  • 16 Ribel-Madsen R, Friedrichsen M, Vaag A, Poulsen P. Retinol-binding protein 4 in twins: regulatory mechanisms and impact of circulating and tissue expression levels on insulin secretion and action. Diabetes 2009; 58: 54-60
    CrossrefPubMedGoogle Scholar
  • 17 DeFronzo RA, Gunnarsson R, Björkman O, Olsson M, Wahren J. Effects of insulin on peripheral and splanchnic glucose metabolism in noninsulin-dependent (type II) diabetes mellitus. J Clin Invest 1985; 76: 149-155
    CrossrefPubMedGoogle Scholar
  • 18 Abel ED, Peroni O, Kim JK, Kim YB, Boss O, Hadro E, Minnemann T, Shulman GI, Kahn BB. Adipose-selective targeting of the GLUT4 gene impairs insulin action in muscle and liver. Nature 2001; 409 (6821) 729-733
    CrossrefPubMedGoogle Scholar
  • 19 Ost A, Danielsson A, Lidén M, Eriksson U, Nystrom FH, Strålfors P. Retinol-binding protein-4 attenuates insulin-induced phosphorylation of IRS1 and ERK1/2 in primary human adipocytes. FASEB J 2007; 21: 3696-3704
    CrossrefPubMedGoogle Scholar
  • 20 Stenkula KG, Said L, Karlsson M, Thorn H, Kjølhede P, Gustavsson J, Söderström M, Strålfors P, Nystrom FH. Expression of a mutant IRS inhibits metabolic and mitogenic signalling of insulin in human adipocytes. Mol Cell Endocrinol 2004; 221: 1-8
    CrossrefPubMedGoogle Scholar
  • 21 Janke J, Engeli S, Boschmann M, Adams F, Böhnke J, Luft FC, Sharma AM, Jordan J. Retinol-binding protein 4 in human obesity. Diabetes 2006; 55: 2805-2810
    CrossrefPubMedGoogle Scholar
  • 22 Yao-Borengasser A, Varma V, Bodles AM, Rasouli N, Phanavanh B, Lee MJ, Starks T, Kern LM, Spencer 3rd HJ, Rashidi AA, McGehee Jr RE, Fried SK, Kern PA. Retinol binding protein 4 expression in humans: relationship to insulin resistance, inflammation, and response to pioglitazone. J Clin Endocrinol Metab 2007; 92: 2590-2597
    CrossrefPubMedGoogle Scholar
  • 23 Zeyda M, Stulnig TM. Obesity inflamation and insulin resistance – A mini-review. Gerontology 2009; 55: 379-386
    CrossrefPubMedGoogle Scholar
  • 24 Balagopal P, Graham TE, Kahn BB, Altomare A, Funanage V, George D. Reduction of elevated serum retinol binding protein in obese children by lifestyle intervention: association with subclinical inflammation. J Clin Endocrinol Metab 2007; 92: 1971-1974
    CrossrefPubMedGoogle Scholar
  • 25 Fleck A. Clinical and nutritional aspects of changes in acute-phase proteins during inflammation. Proc Nutr Soc 1989; 48: 347-354
    CrossrefPubMedGoogle Scholar
  • 26 Zobali F, Avci A, Canbolat O, Karasu C. Effects of vitamin A and insulin on the antioxidative state of diabetic rat heart: a comparison study with combination treatment. Cell Biochem Funct 2002; 20: 75-80
    CrossrefPubMedGoogle Scholar
  • 27 Kos K, Wong S, Tan BK, Kerrigan D, Randeva HS, Pinkney JH, Wilding JP. Human RBP4 adipose tissue expression is gender specific and influenced by leptin. Clin Endocrinol (Oxf) 2011; 74: 197-205
    CrossrefPubMedGoogle Scholar
  • 28 Jia W, Wu H, Bao Y, Wang C, Lu J, Zhu J, Xiang K. Association of serum retinol binding protein 4 and visceral adiposity in Chinese subjects with and without type 2 diabetes. J Clin Endocrinol Metab 2007; 92: 3224-3229
    CrossrefPubMedGoogle Scholar
  • 29 Tetsuya T, Takeshi O, Kengo M, Masako Z, Kunichi K, Yushi H, Hideaki K, Masahiko F, Kazuro S, Masato K. Effects of pioglitazone and metformin on intracellular lipid content in liver and skeletal muscle of individuals with type 2 diabetes mellitus. Metabolism 2007; 56: 1418-1424
    CrossrefPubMedGoogle Scholar
  • 30 Lin KD, Chang YH, Wang CL, Yang YH, Hsiao PJ, Li TH, Shin SJ. Thiazolidinedione addition reduces the serum retinol-binding protein 4 in type 2 diabetic patients treated with metformin and sulfonylurea. Transl Res 2008; 151: 309-314
    CrossrefPubMedGoogle Scholar
  • 31 Pfützner A, Schöndorf T, Hanefeld M, Lübben G, Kann PH, Karagiannis E, Wilhelm B, Forst T. Changes in insulin resistance and cardiovascular risk induced by PPARgamma activation have no impact on RBP4 plasma concentrations in nondiabetic patients. Horm Metab Res 2009; 41: 202-206
    Article in Thieme ConnectPubMedGoogle Scholar
  • 32 You SH, Kim BS, Hong SJ, Ahn CM, Lim DS. The effects of pioglitazone in reducing atherosclerosis progression and neointima volume in type 2 diabetic patients: prospective randomized study with volumetric intravascular ultrasonography analysis. Korean Circ J 2010; 40: 625-631
    CrossrefPubMedGoogle Scholar
  • 33 Derosa G, Maffioli P, Salvadeo SA, Ferrari I, Ragonesi PD, Quersi F, Franzetti IG, Gadaleta G, Ciccarelli L, Piccinni MN, D’Angelo A, Cicero AF. Exenatide versus glibenclamide in patients with diabetes. Diabetes Technol Ther 2010; 12: 233-240
    CrossrefPubMedGoogle Scholar
  • 34 Derosa G, Maffioli P, D’Angelo A, Fogari E, Bianchi L, Cicero AF. Acarbose on insulin resistance after an oral fat load: a double-blind, placebo controlled study. J Diabetes Complications 2011; 25: 258-266
    CrossrefPubMedGoogle Scholar
  • 35 Haider DG, Schindler K, Prager G, Bohdjalian A, Luger A, Wolzt M, Ludvik B. Serum retinol-binding protein 4 is reduced after weight loss in morbidly obese subjects. J Clin Endocrinol Metab 2007; 92: 1168-1171
    PubMedGoogle Scholar
  • 36 Ingelsson E, Sundstrom J, Melhus H, Michaelsson K, Berne C, Vasan RS, Riserus U, Blomhoff R, Lind L, Arnlov J. Circulating retinol-binding protein 4, cardiovascular risk factors and prevalent cardiovascular disease in elderly. Atherosclerosis 2009; 206: 38-39
    CrossrefPubMedGoogle Scholar
  • 37 Qi Q, Yu Z, Ye X, Zhao F, Huang P, Hu FB, Franco OH, Wang J, Li H, Liu Y, Lin X. Elevated Retinol-binding protein 4 levels are associated with Metabolic Syndrome in Chinese people. J Clin Endocrinol Metab 2007; 92: 4827-4834
    CrossrefPubMedGoogle Scholar
  • 38 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
    CrossrefPubMedGoogle Scholar
  • 39 Lee JW, Lee HR, Shim JY, Im JA, Lee DC. Abdominal visceral fat reduction is associated with favorable changes of serum retinol binding protein-4 in nondiabetic subjects. Endocr J 2008; 55: 811-818
    CrossrefPubMedGoogle Scholar
  • 40 Lee JW, Im JA, Lee HR, Shim JY, Youn BS, Lee DC. Visceral adiposity is associated with serum retinol binding protein-4 levels in healthy women. Obesity (Silver Spring) 2007; 15: 2225-2232
    CrossrefPubMedGoogle Scholar
  • 41 Silha JV, Nyommba BLG, 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
    CrossrefPubMedGoogle Scholar
  • 42 Wu H, Jia W, Bao Y, Lu J, Zhu J, Wang R, Chen Y, Xiang K. Serum retinol binding protein4 and nonalcoholic fatty liver disease in patients with type 2 diabetes mellitus. Diabetes Res Clin Pract 2008; 79: 185-190
    CrossrefPubMedGoogle Scholar
  • 43 Seo JA, Kim NH, Park SY, Kim HY, Ryu OH, Lee KW, Lee J, Kim DL, Choi KM, Baik SH, Choi DS, Kim SG. Serum retinol-binding protein 4 levels are elevated in non-alcoholic fatty liver disease. Clin Endocrinol 2008; 68: 555-560
    CrossrefPubMedGoogle Scholar
  • 44 Romanowska A, Lebensztejn DM, Skiba E, Tarasów E, Kaczmarski M. Retinol binding protein-4 as a serum biomarker of intrahepatic lipid content in obese children – preliminary report. Acta Biochim Pol 2011; 58: 35-38
    PubMedGoogle Scholar
  • 45 Perseghin G, Lattuada G, Cobelli FD, Esposito A, Belloni E, Canu T, Ragogna F, Scifo P, Maschio AD, Luzi L. Serum retinol binding protein 4, leptin and adiponectin concentrations are related to ectopic fat accumulation. J Clin Endocrin Metab 2007; 92: 4883-4888
    CrossrefPubMedGoogle Scholar
  • 46 Shin MJ, Kang SM, Jang Y, Lee JH, Oh J, Chung JH, Chung N. Serum retinol binding protein 4 levels are associated with serum adiponectin levels in non-diabetic, non-obese subjects with hypercholesterolemia. Clin Chim Acta 2007; 378: 227-229
    CrossrefPubMedGoogle Scholar
  • 47 Choi SH, Lee YJ, Park YJ, Kim KW, Lee EJ, Lim S, Park do J, Kim SE, Park KS, Jang HC, Cho BY. Retinol binding protein-4 elevation is associated with serum thyroid-stimulating hormone level independently of obesity in elderly subjects with normal glucose tolerance. J Clin Endocrinol Metab 2008; 93: 2313-2318
    CrossrefPubMedGoogle Scholar
  • 48 Makino S, Fujiwara M, Suzukawa K, Handa H, Fujie T, Ohtaka Y, Komatsu Y, Aoki Y, Maruyama H, Terada Y, Hashimoto K, Sugimoto T. Visceral obesity is associated with the metabolic syndrome and elevated plasma retinol binding protein-4 level in obstructive sleep apnea syndrome. Horm Metab Res 2009; 41: 221-226
    Article in Thieme ConnectPubMedGoogle Scholar
  • 49 Lim S, Yoon JW, Choi SH, Park YJ, Lee JJ, Park JH, Lee SB, Kim KW, Lim JY, Kim YB, Park KS, Lee HK, Cho SI, Jang HC. Combined impact of adiponectin and retinol-binding protein 4 on Metabolic Syndrome in elderly people: The Korean Longitudinal Study on Health and Aging. Obesity 2010; 18: 826-832
    CrossrefPubMedGoogle Scholar
  • 50 Sasaki M, Otani T, Kawakami M, Ishikawa S. Elevation of plasma retinol-binding protein 4 and reduction of plasma adiponectin in subjects with cerebral infarction. Metabolism 2010; 59: 527-532
    CrossrefPubMedGoogle Scholar
  • 51 Rhie YJ, Choi BM, Eun SH, Son CS, Park SH, Lee KH. Association of serum retinol binding protein 4 with adiposity and pubertal development in Korean children and adolescents. J Korean Med Sci 2011; 26: 797-802
    CrossrefPubMedGoogle Scholar
  • 52 Usui S, Ichimura M, Ikeda S, Okamoto M. Association between serum retinol-binding protein 4 and small dense low-density lipoprotein cholesterol levels in young adult women. Clin Chim Acta 2009; 399: 45-48
    CrossrefPubMedGoogle Scholar
  • 53 Park SE, Kim DH, Lee JH, Park JS, Kang ES, Ahn CW, Lee HC, Cha BS. Retinol-binding protein-4 is associated with endothelial dysfunction in adults with newly diagnosed type 2 diabetes mellitus. Atherosclerosis 2009; 204: 23-25
    CrossrefPubMedGoogle Scholar
  • 54 Broch M, Auguet MT, Ramírez R, Olona M, Aguilar C, Megia A, Alcaide MJ, Pastor R, Martínez S, Caubet E, Garcia-España A, Richart C. Parallel downregulation of retinol-binding protein-4 and adiponectin expression in subcutaneous adipose tissue of non-morbidly obese subjects. Eur J Endocrinol 2009; 161: 87-94
    CrossrefPubMedGoogle Scholar
  • 55 Shim CY, Park S, Kim JS, Shin DJ, Ko YG, Kang SM, Choi D, Ha JW, Jang Y, Chung N. Association of plasma retinol-binding protein 4, adiponectin, and high molecular weight adiponectin with insulin resistance in non-diabetic hypertensive patients. Yonsei Med J 2010; 51: 375-384
    CrossrefPubMedGoogle Scholar
  • 56 Lim S, Choi SH, Jeong IK, Kim JH, Moon MK, Park KS, Lee HK, Kim YB, Jang HC. Insulin-sensitizing effects of exercise on adiponectin and retinol-binding protein-4 concentrations in young and middle-aged women. J Clin Endocrinol Metab 2008; 93: 2263-2268
    CrossrefPubMedGoogle Scholar
  • 57 Sell H, Eckel J. Regulation of retinol binding protein 4 production in primary human adipocytes by adiponectin, troglitazone and TNF-alpha. Diabetologia 2007; 50: 2221-2223
    CrossrefPubMedGoogle Scholar
  • 58 Guerre-Millo M. Adiponectin: an update. Diabetes Metab 2008; 34: 12-18
    CrossrefPubMedGoogle Scholar
  • 59 Volek JS, Phinney SD, Forsythe CE, Quann EE, Wood RJ, Puglisi MJ, Kraemer WJ, Bibus DM, Fernandez ML, Feinman RD. Carbohydrate restriction has a more favorable impact on the metabolic syndrome than a low fat diet. Lipids 2009; 44: 297-309
    CrossrefPubMedGoogle Scholar
  • 60 Zhang W, Della-Fera MA, Hartzell DL, Hausman D, Baile CA. Adipose tissue gene expression profiles in ob/ob mice treated with leptin. Life Sci 2008; 83: 35-42
    CrossrefPubMedGoogle Scholar
  • 61 Qi Q, Wang J, Li H, Yu Z, Ye X, Hu FB, Franco OH, Pan A, Liu Y, Lin X. Associations of resistin with inflammatory and fibrinolytic markers, insulin resistance, and metabolic syndrome in middle-aged and older Chinese. Eur J Endocrinol 2008; 159: 585-593
    CrossrefPubMedGoogle Scholar
  • 62 Yildiz BO, Bozdag G, Otegen U, Harmanci A, Boynukalin K, Vural Z, Kirazli S, Yarali H. Visfatin and retinol-binding protein 4 concentrations in lean, glucose-tolerant women with PCOS. Reprod Biomed Online 2010; 20: 150-155
    CrossrefPubMedGoogle Scholar
  • 63 Goralski KB, Sinal CJ. Type 2 diabetes and cardiovascular disease: getting to the fat of the matter. Can J Physiol Pharmacol 2007; 85: 113-132
    CrossrefPubMedGoogle Scholar
  • 64 Christou GA, Tellis CC, Elisaf MS, Tselepis AD, Kiortsis DN. The Changes in Plasma Retinol-Binding Protein 4 Levels are Associated With Those of the Apolipoprotein B-Containing Lipoproteins During Dietary and Drug Treatment. Angiology 2011; May 20 Epub ahead of print
    PubMedGoogle Scholar
  • 65 Chan DC, Watts GF, Ng TW, Yamashita S, Barrett PH. Effect of weight loss on markers of triglyceride-rich lipoprotein metabolism in the metabolic syndrome. Eur J Clin Invest 2008; 38: 743-751
    CrossrefPubMedGoogle Scholar
  • 66 Chan DC, Watts GF, Gan S, Wong AT, Ooi EM, Barrett PH. Nonalcoholic fatty liver disease as the transducer of hepatic oversecretion of very-low-density lipoprotein-apolipoprotein B-100 in obesity. Arterioscler Thromb Vasc Biol 2010; 30: 1043-1050
    CrossrefPubMedGoogle Scholar
  • 67 Ng TW, Watts GF, Barrett PH, Rye KA, Chan DC. Effect of weight loss on LDL and HDL kinetics in the Metabolic Syndrome: associations with changes in plasma retinol-binding protein-4 and adiponectin levels. Diabetes Care 2007; 30: 2945-2950
    CrossrefPubMedGoogle Scholar
  • 68 Reinehr T, Stoffel-Wagner B, Roth CL. Retinol-binding protein 4 and its relation to insulin resistance in obese children before and after weight loss. J Clin Endocrinol Metab 2008; 93: 2287-2293
    CrossrefPubMedGoogle Scholar
  • 69 Mitterberger MC, Mattesich M, Klaver E, Lechner S, Engelhardt T, Larcher L, Pierer G, Piza-Katzer H, Zwerschke W. Adipokine profile and insulin sensitivity in formerly obese women subjected to bariatric surgery or diet-induced long-term caloric restriction. J Gerontol A Biol Sci Med Sci 2010; 65: 915-923
    PubMedGoogle Scholar
  • 70 Hermsdorff HH, Zulet MA, Abete I, Martínez JA. Discriminated benefits of a Mediterranean dietary pattern within a hypocaloric diet program on plasma RBP4 concentrations and other inflammatory markers in obese subjects. Endocrine 2009; 36: 445-451
    CrossrefPubMedGoogle Scholar
  • 71 Vitkova M, Klimcakova E, Kovacikova M, Valle C, Moro C, Polak J, Hanacek J, Capel F, Viguerie N, Richterova B, Bajzova M, Hejnova J, Stich V, Langin D. Plasma levels and adipose tissue messenger ribonucleic acid expression of retinol-binding protein 4 are reduced during calorie restriction in obese subjects but are not related to diet-induced changes in insulin sensitivity. J Clin Endocrinol Metab 2007; 92: 2330-2335
    CrossrefPubMedGoogle Scholar
  • 72 Kiortsis DN, Tzotzas T, Giral P, Bruckert E, Beucler I, Valsamides S, Turpin G. Changes in lipoprotein(a) levels and hormonal correlations during a weight reduction program. Nutr Metab Cardiovasc Dis 2001; 11: 153-157
    PubMedGoogle Scholar
  • 73 Yu Z, Ye X, Wang J, Qi Q, Franco OH, Rennie KL, Pan A, Li H, Liu Y, Hu FB, Lin X. Associations of physical activity with inflammatory factors, adipocytokines, and metabolic syndrome in middle-aged and older Chinese people. Circulation 2009; 119: 2969-2977
    CrossrefPubMedGoogle Scholar
  • 74 Ku YH, Han KA, Ahn H, Kwon H, Koo BK, Kim HC, Min KW. Resistance exercise did not alter intramuscular adipose tissue but reduced retinol-binding protein-4 concentration in individuals with type 2 diabetes mellitus. J Int Med Res 2010; 38: 782-791
    CrossrefPubMedGoogle Scholar
  • 75 Choi KM, Kim TN, Yoo HJ, Lee KW, Cho GJ, Hwang TG, Baik SH, Choi DS, Kim SM. Effect of exercise training on A-FABP, lipocalin-2 and RBP4 levels in obese women. Clin Endocrinol (Oxf) 2009; 70: 569-574
    CrossrefPubMedGoogle Scholar
  • 76 Bradley RL, Jeon JY, Liu FF, Maratos-Flier E. Voluntary exercise improves insulin sensitivity and adipose tissue inflammation in diet-induced obese mice. Am J Physiol Endocrinol Metab 2008; 295: E586-E594
    CrossrefPubMedGoogle Scholar
  • 77 Ryan AS. Insulin resistance with aging: effects of diet and exercise. Sports Med 2000; 30: 327-346
    CrossrefPubMedGoogle Scholar
  • 78 Derosa G, Maffioli P, Ferrari I, D’Angelo A, Fogari E, Palumbo I, Randazzo S, Cicero AF. Orlistat and l-carnitine compared to orlistat alone on insulin resistance in obese diabetic patients. Endocr J 2010; 57: 777-786
    CrossrefPubMedGoogle Scholar
  • 79 Derosa G, Maffioli P, Salvadeo SA, Ferrari I, Gravina A, Mereu R, D'Angelo A, Palumbo I, Randazzo S, Cicero AF. Sibutramine and l-carnitine compared to sibutramine alone on insulin resistance in diabetic patients. Intern Med 2010; 49: 1717-1725
    CrossrefPubMedGoogle Scholar
  • 80 Mohapatra J, Sharma M, Singh S, Pandya G, Chatterjee A, Balaraman R, Patel PR, Jain MR. Involvement of adipokines in rimonabant-mediated insulin sensitivity in ob/ob mice. J Pharm Pharmacol 2009; 61: 1493-1498
    CrossrefPubMedGoogle Scholar
  • 81 Swarbrick MM, Stanhope KL, Austrheim-Smith IT, Van Loan MD, Ali MR, Wolfe BM, Havel PJ. Longitudinal changes in pancreatic and adipocyte hormones following Roux-en-Y gastric bypass surgery. Diabetologia 2008; 51: 1901-1911
    CrossrefPubMedGoogle Scholar
  • 82 Broch M, Gómez JM, Auguet MT, Vilarrasa N, Pastor R, Elio I, Olona M, García-España A, Richart C. Association of retinol-binding protein-4 (RBP4) with lipid parameters in obese women. Obes Surg 2010; 20: 1258-1264
    CrossrefPubMedGoogle Scholar
  • 83 Gómez-Ambrosi J, Rodríguez A, Catalán V, Ramírez B, Silva C, Rotellar F, Gil MJ, Salvador J, Frühbeck G. Serum retinol-binding protein 4 is not increased in obesity or obesity-associated type 2 diabetes mellitus, but is reduced after relevant reductions in body fat following gastric bypass. Clin Endocrinol (Oxf) 2008; 69: 208-215
    CrossrefPubMedGoogle Scholar
  • 84 Tschoner A, Sturm W, Engl J, Kaser S, Laimer M, Laimer E, Weiss H, Patsch JR, Ebenbichler CF. Retinol-binding protein 4, visceral fat, and the metabolic syndrome: effects of weight loss. Obesity 2008; 16: 2439-2444
    CrossrefPubMedGoogle Scholar
  • 85 Lin CC, Lai MM, Li TC, Li CI, Liu CS, Chen CC, Wu MT. Relationship between serum retinol-binding protein 4 and visfatin and the metabolic syndrome. Diabetes Res Clin Pract 2009; 85: 24-29
    CrossrefPubMedGoogle Scholar
  • 86 Yoshida A, Matsutani Y, Fukuchi Y, Saito K, Naito M. Analysis of the factors contributing to serum retinol binding protein and transthyreyin levels in Japanese adults. J Atheroscler Thromb 2006; 13: 209-215
    CrossrefPubMedGoogle Scholar
  • 87 Mallat Z, Simon T, Benessiano J, Clement K, Taleb S, Wareham NJ, Luben R, Khaw KT, Tedgui A, Boekholdt SM. Retinol-binding protein 4 and prediction of incident coronary events in healthy men and women. J Clin Endocrinol Metab 2009; 94: 255-260
    PubMedGoogle Scholar
  • 88 Von Eyatten M, Lepper PM, Liu D, Lang K, Baumann M, Nawroth PP, Bierhaus A, Dugi KA, Heemann U, Allolio B, Humpert PM. Retinol-binding protein 4 is associated with components of the metabolic syndrome, but not with insulin resistance, in men with type 2 diabetes or coronary artery disease. Diabetologia 2007; 50: 1930-1937
    CrossrefPubMedGoogle Scholar
  • 89 Schaefer EJ, Lamon-Fava S, Ordovas JM, Cohn SD, Schaefer MM, Castelli WP, Wilson PW. Factors associated with low and elevated plasma high density lipoprotein cholesterol and apolipoprotein A-I levels in the Framingham Offspring Study. J Lipid Res 1994; 35: 871-882
    PubMedGoogle Scholar
  • 90 Friedewald WT, Levy RI, Frederickson DS. Estimation of the concentration of low-density lipoprotein cholesterol in plasma, without use of the preparative ultracentrifuge. Clin Chem 1972; 18: 499-502
    CrossrefPubMedGoogle Scholar
  • 91 National Cholesterol Education Program. Third Report of the National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III) final report. Circulation 2002; 106: 3143-3421
    PubMedGoogle Scholar
  • 92 Berneis KK, Krauss RM. Metabolic origins and clinical significance of LDL heterogeneity. J Lipid Res 2002; 43: 1363-1379
    CrossrefPubMedGoogle Scholar
  • 93 Muggeo M, Zenti MG, Travia D, Sartori A, Trimloni S, Grigolini L, Graziani MS, Cigolini M. Serum retinol levels throughout 2 years of cholesterol-lowering therapy. Metabolism 1995; 44: 398-403
    CrossrefPubMedGoogle Scholar
  • 94 Szendroedi J, Anderwald C, Krssak M, Bayerle-Eder M, Esterbauer H, Pfeiler G, Brehm A, Nowotny P, Hofer A, Waldhausl W, Roden M. Effects of high-dose simvastatin therapy on glucose metabolism and ectopic lipid deposition in nonobese type 2 diabetic patients. Diabetes Care 2009; 32: 209-214
    CrossrefPubMedGoogle Scholar
  • 95 Takebayashi K, Suetsugu M, Matsumoto S, Aso Y, Inukai T. Effects of rosuvastatin and colestimide on metabolic parameters and urinary monocyte chemoattractant protein-1 in type 2 diabetic patients with hyperlipidemia. South Med J 2009; 102: 361-368
    CrossrefPubMedGoogle Scholar
  • 96 Wu H, Wei L, Bao Y, Lu J, Huamg P, Liu Y, Jia W, Xiang K. Fenofibrate reduces serum retinil-binding protein-4 by suppressing its expression in adipose tissue. Am J Physiol Endocrinol Metab 2009; 296: 628-634
    CrossrefPubMedGoogle Scholar
  • 97 Piscator M. Early detection of tubular dysfunction. Kidney Int Suppl 1991; 34: S15-S17
    PubMedGoogle Scholar
  • 98 Chan DC, Watts GF, Gan SK, Ooi EM, Barrett PH. Effect of ezetimibe on hepatic fat, inflammatory markers, and apolipoprotein B-100 kinetics in insulin-resistant obese subjects on a weight loss diet. Diabetes Care 2010; 33: 1134-1139
    CrossrefPubMedGoogle Scholar
  • 99 Ingelsson E, Lind L. Circulating retinol binding protein 4 and subclinical cardiovascular disease in the elderly. Diabetes Care 2009; 32: 733-735
    CrossrefPubMedGoogle Scholar
  • 100 Solini A, Santini E, Madec S, Rossi C, Muscelli E. Retinol-binding protein-4 in women with untreated essential hypertension. Am J Hypertens 2009; 22: 1001-1006
    CrossrefPubMedGoogle Scholar
  • 101 Bobbert T, Raila J, Schwarz F, Mai K, Henze A, Pfeiffer AF, Schweigert FJ, Spranger J. Relation between retinol, retinol-binding protein 4, transthyretin and carotid intima media thickness. Atherosclerosis 2010; 213: 549-551
    CrossrefPubMedGoogle Scholar
  • 102 Christensen EI, Moskaug JO, Vorum H, Jacobsen C, Gundersen TE, Nykjaer A, Blomhoff R, Willnow TE, Moestrup SK. Evidence for an essential role of megalin in transepithelial transport of retinol. J Am Soc Nephrol 1999; 10: 685-695
    PubMedGoogle Scholar
  • 103 Raila J, Willnow TE, Schweigert FJ. Megalin-mediated reuptake of retinol in the kidneys of mice is essential for vitamin A homeostasis. J Nutr 2005; 135: 2512-2516
    PubMedGoogle Scholar
  • 104 Ziegelmeier M, Bachmann A, Seeger J, Lossner U, Kratzsch J, Blüher M, Stumvoll M, Fasshauer M. Serum levels of adipokine retinol-binding protein-4 in relation to renal function. Diabetes Care 2007; 30: 2588-2592
    CrossrefPubMedGoogle Scholar
  • 105 Chang YH, Lin KD, Wang CL, Hsieh MC, Hsiao PJ, Shin SJ. Elevated serum retinol-binding protein 4 concentrations are associated with renal dysfunction and uric acid in type 2 diabetic patients. Diabetes Metab Res Rev 2008; 24: 629-634
    CrossrefPubMedGoogle Scholar
  • 106 Graham TE, Wason CJ, Blüher M, Kahn BB. Shortcomings in methodology complicate measurements of serum retinol binding protein (RBP4) in insulin-resistant human subjects. Diabetologia 2007; 50: 814-823
    CrossrefPubMedGoogle Scholar
  • 107 Promintzer M, Krebs M, Todoric J, Luger A, Bischof MG, Nowotny P, Wagner O, Esterbauer H, Anderwald C. Insulin resistance is unrelated to circulating retinol binding protein and protein C inhibitor. J Clin Endocrinol Metab 2007; 92: 4306-4312
    CrossrefPubMedGoogle Scholar
  • 108 Gavi S, Qurashi S, Stuart LM, Lau R, Melendez MM, Mynarcik DC, McNurlan MA, Gelato MC. Influence of age on the association of retinol-binding protein 4 with metabolic syndrome. Obesity (Silver Spring) 2008; 16: 893-895
    CrossrefPubMedGoogle Scholar