This Article Full Text Full Text (PDF) Submit a related Letter to the Editor Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Copyright Permission Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Lee, J. H. Articles by Mantzoros, C. S. Search for Related Content PubMed PubMed Citation Articles by Lee, J. H. Articles by Mantzoros, C. S.

Circulating Resistin Levels Are Not Associated with Obesity or Insulin Resistance in Humans and Are Not Regulated by Fasting or Leptin Administration: Cross-Sectional and Interventional Studies in Normal, Insulin-Resistant, and Diabetic Subjects

Division of Endocrinology, Diabetes, and Metabolism (J.H.L., J.L.C., C.O., C.S.M.), Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts 02215; Harokopio University (N.Y., M.K.), Athens, Greece 17671; Division of Endocrinology (E.E.), Connecticut Children’s Medical Center, University of Connecticut School of Medicine, Hartford, Connecticut 06106; and Preventative Cardiology Program (R.S.), Division of Cardiology, Hartford Hospital, Hartford, Connecticut 06102

Address all correspondence and requests for reprints to: Christos S. Mantzoros, M.D., Division of Endocrinology, Diabetes, and Metabolism, Department of Internal Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, 330 Brookline Avenue, Stoneman 816, Boston, Massachusetts 02215. E-mail: cmantzor{at}bidmc.harvard.edu.

Resistin is a novel adipocyte-secreted hormone proposed to link obesity with diabetes. Studies in mice have revealed conflicting data however, and the physiological role of circulating resistin in humans remains unknown. We conducted cross-sectional studies in 123 middle-aged women and 120 healthy young subjects and found that serum resistin levels did not correlate with markers of adiposity, including body mass index, waist-to-hip ratio, or fat mass, or insulin resistance assessed by homeostasis model, lipid profile, or serum leptin levels; but females had higher resistin levels than males (P < 0.02). We also found no difference in serum resistin levels between lean healthy and obese insulin-resistant nondiabetic and type 2 diabetic adolescents. Finally, to evaluate the effect of food deprivation and/or leptin administration on resistin levels, we performed interventional studies that revealed no significant difference in resistin levels after 48 h of fasting and/or leptin administration at either physiological or pharmacological doses. We conclude that circulating resistin is unlikely to play a major role in insulin resistance or energy homeostasis in humans.

This work was supported by National Institute of Diabetes and Digestive and Kidney Diseases Grant DK 58785; National Institutes of Health Grants MO1-RR01032, K30-HL04095, and 5T32DK07516-18; Amgen grant (to C.S.M.); and an Eli Lilly and Co. fellowship award.

Abbreviations: BIA, Bioelectrical impedance analysis; BMI, body mass index; CV, coefficient of variation; DEXA, dual-energy x-ray absorptiometry; FM, fat mass; %FM, percent fat mass; HOMA, homeostasis model assessment; IR, insulin resistance; RELM, resistin-like molecule; r-metHuLeptin, recombinant methionyl human leptin; T2DM, type 2 diabetes; TZD, thiazolidinedione; WC, waist circumference; WHR, waist-hip ratio.

This article has been cited by other articles:

				T. Tomaru, D. J. Steger, M. I. Lefterova, M. Schupp, and M. A. Lazar Adipocyte-specific Expression of Murine Resistin Is Mediated by Synergism between Peroxisome Proliferator-activated Receptor {gamma} and CCAAT/Enhancer-binding Proteins J. Biol. Chem., March 6, 2009; 284(10): 6116 - 6125. [Abstract] [Full Text] [PDF]

				M G. Shaikh, R. G Grundy, and J. M W Kirk Hyperleptinaemia rather than fasting hyperinsulinaemia is associated with obesity following hypothalamic damage in children Eur. J. Endocrinol., December 1, 2008; 159(6): 791 - 797. [Abstract] [Full Text] [PDF]

				J. L Fargnoli, T. T Fung, D. M Olenczuk, J. P Chamberland, F. B Hu, and C. S Mantzoros Adherence to healthy eating patterns is associated with higher circulating total and high-molecular-weight adiponectin and lower resistin concentrations in women from the Nurses' Health Study Am. J. Clinical Nutrition, November 1, 2008; 88(5): 1213 - 1224. [Abstract] [Full Text] [PDF]

				Q. Qi, J. Wang, H. Li, Z. Yu, X. Ye, F. B Hu, O. H Franco, A. Pan, Y. Liu, and X. Lin Associations of resistin with inflammatory and fibrinolytic markers, insulin resistance, and metabolic syndrome in middle-aged and older Chinese Eur. J. Endocrinol., November 1, 2008; 159(5): 585 - 593. [Abstract] [Full Text] [PDF]

				N. Rasouli and P. A. Kern Adipocytokines and the Metabolic Complications of Obesity J. Clin. Endocrinol. Metab., November 1, 2008; 93(11_Supplement_1): s64 - s73. [Abstract] [Full Text] [PDF]

				C. Heidemann, Q. Sun, R. M. van Dam, J. B. Meigs, C. Zhang, S. S. Tworoger, C. S. Mantzoros, and F. B. Hu Total and High-Molecular-Weight Adiponectin and Resistin in Relation to the Risk for Type 2 Diabetes in Women Ann Intern Med, September 2, 2008; 149(5): 307 - 316. [Abstract] [Full Text] [PDF]

				M.-F. Hivert, L. M. Sullivan, C. S. Fox, D. M. Nathan, R. B. D'Agostino Sr., P. W. F. Wilson, and J. B. Meigs Associations of Adiponectin, Resistin, and Tumor Necrosis Factor-{alpha} with Insulin Resistance J. Clin. Endocrinol. Metab., August 1, 2008; 93(8): 3165 - 3172. [Abstract] [Full Text] [PDF]

				C. Weikert, S. Westphal, K. Berger, J. Dierkes, M. Mohlig, J. Spranger, E. B. Rimm, S. N. Willich, H. Boeing, and T. Pischon Plasma Resistin Levels and Risk of Myocardial Infarction and Ischemic Stroke J. Clin. Endocrinol. Metab., July 1, 2008; 93(7): 2647 - 2653. [Abstract] [Full Text] [PDF]

				R. S. Ahima and M. A. Lazar Adipokines and the Peripheral and Neural Control of Energy Balance Mol. Endocrinol., May 1, 2008; 22(5): 1023 - 1031. [Abstract] [Full Text] [PDF]

				T. Saito, N. Yamaguchi, Y. Shimazaki, H. Hayashida, K. Yonemoto, Y. Doi, Y. Kiyohara, M. Iida, and Y. Yamashita Serum Levels of Resistin and Adiponectin in Women with Periodontitis: the Hisayama Study Journal of Dental Research, April 1, 2008; 87(4): 319 - 322. [Abstract] [Full Text] [PDF]

				F. F. Chehab Minireview: Obesity and LipOdystrophy--Where Do the Circles Intersect? Endocrinology, March 1, 2008; 149(3): 925 - 934. [Abstract] [Full Text] [PDF]

				M. T. Gentile, C. Vecchione, G. Marino, A. Aretini, A. Di Pardo, G. Antenucci, A. Maffei, G. Cifelli, L. Iorio, A. Landolfi, et al. Resistin Impairs Insulin-Evoked Vasodilation Diabetes, March 1, 2008; 57(3): 577 - 583. [Abstract] [Full Text] [PDF]

				M. Korbonits, D. Blaine, M. Elia, and J. Powell-Tuck Metabolic and hormonal changes during the refeeding period of prolonged fasting Eur. J. Endocrinol., August 1, 2007; 157(2): 157 - 166. [Abstract] [Full Text] [PDF]

				J. D. Knudson, G. M. Dick, and J. D. Tune Adipokines and Coronary Vasomotor Dysfunction Experimental Biology and Medicine, June 1, 2007; 232(6): 727 - 736. [Abstract] [Full Text] [PDF]

				H. Osawa, Y. Tabara, R. Kawamoto, J. Ohashi, M. Ochi, H. Onuma, W. Nishida, K. Yamada, J. Nakura, K. Kohara, et al. Plasma Resistin, Associated With Single Nucleotide Polymorphism -420, Is Correlated With Insulin Resistance, Lower HDL Cholesterol, and High-Sensitivity C-Reactive Protein in the Japanese General Population Diabetes Care, June 1, 2007; 30(6): 1501 - 1506. [Abstract] [Full Text] [PDF]

				G. Fantuzzi and T. Mazzone Adipose Tissue and Atherosclerosis: Exploring the Connection Arterioscler. Thromb. Vasc. Biol., May 1, 2007; 27(5): 996 - 1003. [Abstract] [Full Text] [PDF]

				L Senolt, D Housa, Z Vernerova, T Jirasek, R Svobodova, D Veigl, K Anderlova, U Muller-Ladner, K Pavelka, and M Haluzik Resistin in rheumatoid arthritis synovial tissue, synovial fluid and serum Ann Rheum Dis, April 1, 2007; 66(4): 458 - 463. [Abstract] [Full Text] [PDF]

				G D Norata, M Ongari, K Garlaschelli, S Raselli, L Grigore, and A L Catapano Plasma resistin levels correlate with determinants of the metabolic syndrome Eur. J. Endocrinol., February 1, 2007; 156(2): 279 - 284. [Abstract] [Full Text] [PDF]

				I Pantsulaia, G Livshits, S Trofimov, and E Kobyliansky Genetic and environmental determinants of circulating resistin level in a community-based sample Eur. J. Endocrinol., January 1, 2007; 156(1): 129 - 135. [Abstract] [Full Text] [PDF]

				R. H. Willemsen, M. van Dijk, Y. B. de Rijke, A. W. van Toorenenbergen, P. G. Mulder, and A. C. Hokken-Koelega Effect of Growth Hormone Therapy on Serum Adiponectin and Resistin Levels in Short, Small-for-Gestational-Age Children and Associations with Cardiovascular Risk Parameters J. Clin. Endocrinol. Metab., January 1, 2007; 92(1): 117 - 123. [Abstract] [Full Text] [PDF]

				G. M. Dick, P. S. Katz, M. Farias III, M. Morris, J. James, J. D. Knudson, and J. D. Tune Resistin impairs endothelium-dependent dilation to bradykinin, but not acetylcholine, in the coronary circulation Am J Physiol Heart Circ Physiol, December 1, 2006; 291(6): H2997 - H3002. [Abstract] [Full Text] [PDF]

				G. A Martos-Moreno, V. Barrios, L. Soriano-Guillen, and J. Argente Relationship between adiponectin levels, acylated ghrelin levels, and short-term body mass index changes in children with diabetes mellitus type 1 at diagnosis and after insulin therapy. Eur. J. Endocrinol., November 1, 2006; 155(5): 757 - 761. [Abstract] [Full Text] [PDF]

				G. A Martos-Moreno, V. Barrios, and J. Argente Normative data for adiponectin, resistin, interleukin 6, and leptin/receptor ratio in a healthy Spanish pediatric population: relationship with sex steroids Eur. J. Endocrinol., September 1, 2006; 155(3): 429 - 434. [Abstract] [Full Text] [PDF]

				H.F. Escobar-Morreale, G. Villuendas, J.I. Botella-Carretero, F. Alvarez-Blasco, R. Sanchon, M. Luque-Ramirez, and J.L. San Millan Adiponectin and resistin in PCOS: a clinical, biochemical and molecular genetic study Hum. Reprod., September 1, 2006; 21(9): 2257 - 2265. [Abstract] [Full Text] [PDF]

				M. J. Bahr, J. Ockenga, K. H. W. Boker, M. P. Manns, and U. J. F. Tietge Elevated resistin levels in cirrhosis are associated with the proinflammatory state and altered hepatic glucose metabolism but not with insulin resistance Am J Physiol Endocrinol Metab, August 1, 2006; 291(2): E199 - E206. [Abstract] [Full Text] [PDF]

				A. Kunnari, O. Ukkola, M. Paivansalo, and Y. A. Kesaniemi High Plasma Resistin Level Is Associated with Enhanced Highly Sensitive C-Reactive Protein and Leukocytes J. Clin. Endocrinol. Metab., July 1, 2006; 91(7): 2755 - 2760. [Abstract] [Full Text] [PDF]

				C. Pagano, G. Soardo, C. Pilon, C. Milocco, L. Basan, G. Milan, D. Donnini, D. Faggian, M. Mussap, M. Plebani, et al. Increased Serum Resistin in Nonalcoholic Fatty Liver Disease Is Related to Liver Disease Severity and Not to Insulin Resistance J. Clin. Endocrinol. Metab., March 1, 2006; 91(3): 1081 - 1086. [Abstract] [Full Text] [PDF]

				F. Haugen, T. Ranheim, N. K. Harsem, E. Lips, A. C. Staff, and C. A. Drevon Increased plasma levels of adipokines in preeclampsia: relationship to placenta and adipose tissue gene expression Am J Physiol Endocrinol Metab, February 1, 2006; 290(2): E326 - E333. [Abstract] [Full Text] [PDF]

				K.-D. Nusken, J. Kratzsch, V. Wienholz, W. Stohr, W. Rascher, and J. Dotsch Circulating resistin concentrations in children depend on renal function Nephrol. Dial. Transplant., January 1, 2006; 21(1): 107 - 112. [Abstract] [Full Text] [PDF]

				M. S. Burnett, J. M. Devaney, R. J. Adenika, R. Lindsay, and B. V. Howard Cross-Sectional Associations of Resistin, Coronary Heart Disease, and Insulin Resistance J. Clin. Endocrinol. Metab., January 1, 2006; 91(1): 64 - 68. [Abstract] [Full Text] [PDF]

				M.-P. Chen, F.-M. Chung, D.-M. Chang, J. C.-R. Tsai, H.-F. Huang, S.-J. Shin, and Y.-J. Lee Elevated Plasma Level of Visfatin/Pre-B Cell Colony-Enhancing Factor in Patients with Type 2 Diabetes Mellitus J. Clin. Endocrinol. Metab., January 1, 2006; 91(1): 295 - 299. [Abstract] [Full Text] [PDF]

				H. S. Jung, K.-H. Park, Y. M. Cho, S. S. Chung, H. J. Cho, S. Y. Cho, S. J. Kim, S. Y. Kim, H. K. Lee, and K. S. Park Resistin is secreted from macrophages in atheromas and promotes atherosclerosis Cardiovasc Res, January 1, 2006; 69(1): 76 - 85. [Abstract] [Full Text] [PDF]

				A. Kushiyama, N. Shojima, T. Ogihara, K. Inukai, H. Sakoda, M. Fujishiro, Y. Fukushima, M. Anai, H. Ono, N. Horike, et al. Resistin-like Molecule {beta} Activates MAPKs, Suppresses Insulin Signaling in Hepatocytes, and Induces Diabetes, Hyperlipidemia, and Fatty Liver in Transgenic Mice on a High Fat Diet J. Biol. Chem., December 23, 2005; 280(51): 42016 - 42025. [Abstract] [Full Text] [PDF]

				M Mitchell, D T Armstrong, R L Robker, and R J Norman Adipokines: implications for female fertility and obesity Reproduction, November 1, 2005; 130(5): 583 - 597. [Abstract] [Full Text] [PDF]

				A.-M. Mustonen, S. Saarela, T. Pyykonen, and P. Nieminen Endocrinologic Adaptations to Wintertime Fasting in the Male American Mink (Mustela vison) Experimental Biology and Medicine, October 1, 2005; 230(9): 612 - 620. [Abstract] [Full Text] [PDF]

				D. Barb, S. G. Wadhwa, J. Kratzsch, A. Gavrila, J. L. Chan, C. J. Williams, A. W. Karchmer, and C. S. Mantzoros Circulating Resistin Levels Are Not Associated with Fat Redistribution, Insulin Resistance, or Metabolic Profile in Patients with the Highly Active Antiretroviral Therapy-Induced Metabolic Syndrome J. Clin. Endocrinol. Metab., September 1, 2005; 90(9): 5324 - 5328. [Abstract] [Full Text] [PDF]

				J. R. Berggren, M. W. Hulver, and J. A. Houmard Fat as an endocrine organ: influence of exercise J Appl Physiol, August 1, 2005; 99(2): 757 - 764. [Abstract] [Full Text] [PDF]

				G. E Krassas, N. Pontikides, K. Loustis, G. Koliakos, T. Constantinidis, and D. Panidis Resistin levels in hyperthyroid patients before and after restoration of thyroid function: relationship with body weight and body composition Eur. J. Endocrinol., August 1, 2005; 153(2): 217 - 221. [Abstract] [Full Text] [PDF]

				I. Munir, H.-W. Yen, T. Baruth, R. Tarkowski, R. Azziz, D. A. Magoffin, and A. J. Jakimiuk Resistin Stimulation of 17{alpha}-Hydroxylase Activity in Ovarian Theca Cells in Vitro: Relevance to Polycystic Ovary Syndrome J. Clin. Endocrinol. Metab., August 1, 2005; 90(8): 4852 - 4857. [Abstract] [Full Text] [PDF]

				M. Gerber, A. Boettner, B. Seidel, A. Lammert, J. Bar, E. Schuster, J. Thiery, W. Kiess, and J. Kratzsch Serum Resistin Levels of Obese and Lean Children and Adolescents: Biochemical Analysis and Clinical Relevance J. Clin. Endocrinol. Metab., August 1, 2005; 90(8): 4503 - 4509. [Abstract] [Full Text] [PDF]

				C. Pagano, O. Marin, A. Calcagno, P. Schiappelli, C. Pilon, G. Milan, M. Bertelli, E. Fanin, G. Andrighetto, G. Federspil, et al. Increased Serum Resistin in Adults with Prader-Willi Syndrome Is Related to Obesity and Not to Insulin Resistance J. Clin. Endocrinol. Metab., July 1, 2005; 90(7): 4335 - 4340. [Abstract] [Full Text] [PDF]

				D. Kamin, C. Hadigan, M. Lehrke, S. Mazza, M. A. Lazar, and S. Grinspoon Resistin Levels in Human Immunodeficiency Virus-Infected Patients with Lipoatrophy Decrease in Response to Rosiglitazone J. Clin. Endocrinol. Metab., June 1, 2005; 90(6): 3423 - 3426. [Abstract] [Full Text] [PDF]

				T. Ort, A. A. Arjona, J. R. MacDougall, P. J. Nelson, M. E. Rothenberg, F. Wu, A. Eisen, and Y.-D. C. Halvorsen Recombinant Human FIZZ3/Resistin Stimulates Lipolysis in Cultured Human Adipocytes, Mouse Adipose Explants, and Normal Mice Endocrinology, May 1, 2005; 146(5): 2200 - 2209. [Abstract] [Full Text] [PDF]

				M. Bokarewa, I. Nagaev, L. Dahlberg, U. Smith, and A. Tarkowski Resistin, an Adipokine with Potent Proinflammatory Properties J. Immunol., May 1, 2005; 174(9): 5789 - 5795. [Abstract] [Full Text] [PDF]

				J. Svensson, H. Herlitz, P.-A. Lundberg, and G. Johannsson Adiponectin, Leptin, and Erythrocyte Sodium/Lithium Countertransport Activity, But Not Resistin, Are Related to Glucose Metabolism in Growth Hormone-Deficient Adults J. Clin. Endocrinol. Metab., April 1, 2005; 90(4): 2290 - 2296. [Abstract] [Full Text] [PDF]

				E Carmina, F Orio, S Palomba, T Cascella, R A Longo, A M Colao, G Lombardi, and R A Lobo Evidence for altered adipocyte function in polycystic ovary syndrome Eur. J. Endocrinol., March 1, 2005; 152(3): 389 - 394. [Abstract] [Full Text] [PDF]

				J. H. Lee, J. W. Bullen Jr., V. L. Stoyneva, and C. S. Mantzoros Circulating resistin in lean, obese, and insulin-resistant mouse models: lack of association with insulinemia and glycemia Am J Physiol Endocrinol Metab, March 1, 2005; 288(3): E625 - E632. [Abstract] [Full Text] [PDF]

				M. P. Reilly, M. Lehrke, M. L. Wolfe, A. Rohatgi, M. A. Lazar, and D. J. Rader Resistin Is an Inflammatory Marker of Atherosclerosis in Humans Circulation, February 22, 2005; 111(7): 932 - 939. [Abstract] [Full Text] [PDF]

				G. K. Shetty, P. A. Economides, E. S. Horton, C. S. Mantzoros, and A. Veves Circulating Adiponectin and Resistin Levels in Relation to Metabolic Factors, Inflammatory Markers, and Vascular Reactivity in Diabetic Patients and Subjects at Risk for Diabetes Diabetes Care, October 1, 2004; 27(10): 2450 - 2457. [Abstract] [Full Text] [PDF]

				M.-L. Delporte, S. A. El Mkadem, M. Quisquater, and S. M. Brichard Leptin treatment markedly increased plasma adiponectin but barely decreased plasma resistin of ob/ob mice Am J Physiol Endocrinol Metab, September 1, 2004; 287(3): E446 - E453. [Abstract] [Full Text] [PDF]

				L. K. Heilbronn, J. Rood, L. Janderova, J. B. Albu, D. E. Kelley, E. Ravussin, and S. R. Smith Relationship between Serum Resistin Concentrations and Insulin Resistance in Nonobese, Obese, and Obese Diabetic Subjects J. Clin. Endocrinol. Metab., April 1, 2004; 89(4): 1844 - 1848. [Abstract] [Full Text] [PDF]

				J. V. Silha and L. J. Murphy Serum Resistin (FIZZ3) Protein Is Increased in Obese Humans J. Clin. Endocrinol. Metab., April 1, 2004; 89(4): 1977 - 1977. [Full Text] [PDF]

				M. Degawa-Yamauchi, J. E. Bovenkerk, B. E. Juliar, W. Watson, K. Kerr, R. Jones, and R. V. Considine Authors' Response: Serum Resistin (FIZZ3) Protein Is Increased in Obese Humans J. Clin. Endocrinol. Metab., April 1, 2004; 89(4): 1977 - 1978. [Full Text] [PDF]

				F. Felipe, M. L. Bonet, J. Ribot, and A. Palou Modulation of Resistin Expression by Retinoic Acid and Vitamin A Status Diabetes, April 1, 2004; 53(4): 882 - 889. [Abstract] [Full Text] [PDF]

				J. L. Chan, J. Bullen, J. H. Lee, N. Yiannakouris, and C. S. Mantzoros Ghrelin Levels Are Not Regulated by Recombinant Leptin Administration and/or Three Days of Fasting in Healthy Subjects J. Clin. Endocrinol. Metab., January 1, 2004; 89(1): 335 - 343. [Abstract] [Full Text] [PDF]