This Article Full Text Full Text (PDF) A correction has been published 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 Ozata, M. Articles by Licinio, J. Search for Related Content PubMed PubMed Citation Articles by Ozata, M. Articles by Licinio, J.

Human Leptin Deficiency Caused by a Missense Mutation: Multiple Endocrine Defects, Decreased Sympathetic Tone, and Immune System Dysfunction Indicate New Targets for Leptin Action, Greater Central than Peripheral Resistance to the Effects of Leptin, and Spontaneous Correction of Leptin-Mediated Defects

Department of Endocrinology and Metabolism, Gulhane School of Medicine (M.O., I.C.O.), Etlik-Ankara 06018, Turkey; and the Clinical Neuroendocrinology Branch, National Institute of Mental Health, National Institutes of Health (J.L.), Bethesda, Maryland 20892-1284

Address all correspondence and requests for reprints to: Julio Licinio, M.D., UCLA Department of Psychology, 3554 Gonda Center, 695 Charles Young Drive South, Los Angeles, California 90095. E-mail: licinio{at}ucla.edu

We have previously demonstrated that genetically based leptin deficiency due to a missense leptin gene mutation in a highly consanguineous extended Turkish pedigree is associated with morbid obesity and hypogonadism. We have now performed detailed assessments of endocrine, sympathetic, and immune function. We have also identified a new adult female homozygous patient in this extended family who is severely obese and amenorrheic. In this family all wild-type and heterozygous individuals have normal body weight. Seven obese members of this family, whom we presume to have been leptin deficient, died during childhood. There are several findings that indicate potentially novel targets for leptin action in humans. Four homozygous patients (1 adult male, 2 adult females, and 1 child) have sympathetic system dysfunction, whereas all heterozygous subjects have normal sympathetic system function. Despite sympathetic system dysfunction and postural hypotension, 1 of 3 homozygous adult patients has impaired renin-aldosterone function. The patients also exhibit alterations in GH and PTH-calcium function, and 1 of them has decreased bone mineral density. Despite their obesity, these patients do not have risk factors for cardiovascular disease, such as hypertension, impairments in lipid metabolism, or hyperglycemia. These data support the hypothesis that the obese may have central, but not peripheral, resistance to the effects of leptin and that hyperglycemia may mediate the cardiovascular morbidity of the obese who are not leptin deficient. Furthermore, these data indicate that there may be several new targets for leptin action in human physiology. Such new targets may lead to novel pharmacological strategies for the use of leptin agonists and antagonists in the treatment of human disease. All 19 normal weight individuals in this family are alive, whereas 7 of 11 obese individuals died in childhood after infections. The odds ratio for mortality in the context of this obesity phenotype is 25.4, indicating that this mutation severely impairs key biological functions during childhood, negatively impacting on survival. We found that only the obese child in this family had thyroid function abnormalities. The oldest homozygous female patient started to menstruate, albeit with a luteal phase defect, 7 months ago, after a delay of over 20 yr, whereas the younger adult subjects are still hypogonadic. Thus, we conclude that due to their long life span, humans who survive the negative effects of leptin deficiency during childhood can, in contrast to ob/ob mice, over decades compensate some of the effects of leptin deficiency on immunity and endocrine function through mechanisms that remain to be elucidated.

This article has been cited by other articles:

				C. POPA, M. G. NETEA, J. de GRAAF, F. H.J. van den HOOGEN, T. R.D.J. RADSTAKE, H. TOENHAKE-DIJKSTRA, P. L.C.M. van RIEL, J. W.M. van der MEER, A. F.H. STALENHOEF, and P. BARRERA Circulating Leptin and Adiponectin Concentrations During Tumor Necrosis Factor Blockade in Patients with Active Rheumatoid Arthritis J Rheumatol, April 1, 2009; 36(4): 724 - 730. [Abstract] [Full Text] [PDF]

				S. Bluher and C. S Mantzoros Leptin in humans: lessons from translational research Am. J. Clinical Nutrition, March 1, 2009; 89(3): 991S - 997S. [Abstract] [Full Text] [PDF]

				J. M Friedman Leptin at 14 y of age: an ongoing story Am. J. Clinical Nutrition, March 1, 2009; 89(3): 973S - 979S. [Abstract] [Full Text] [PDF]

				I S. Farooqi and S. O'Rahilly Leptin: a pivotal regulator of human energy homeostasis Am. J. Clinical Nutrition, March 1, 2009; 89(3): 980S - 984S. [Abstract] [Full Text] [PDF]

				E. A. Oral and C. Burant Leptin and insulin resistance: good, bad, or still unclear? Am J Physiol Endocrinol Metab, February 1, 2009; 296(2): E394 - E395. [Full Text] [PDF]

				A. Silvani, S. Bastianini, C. Berteotti, C. Franzini, P. Lenzi, V. Lo Martire, and G. Zoccoli Sleep Modulates Hypertension in Leptin-Deficient Obese Mice Hypertension, February 1, 2009; 53(2): 251 - 255. [Abstract] [Full Text] [PDF]

				G. R. Hajer, T. W. van Haeften, and F. L.J. Visseren Adipose tissue dysfunction in obesity, diabetes, and vascular diseases Eur. Heart J., December 2, 2008; 29(24): 2959 - 2971. [Abstract] [Full Text] [PDF]

				D. A. Morgan, D. R. Thedens, R. Weiss, and K. Rahmouni Mechanisms mediating renal sympathetic activation to leptin in obesity Am J Physiol Regulatory Integrative Comp Physiol, December 1, 2008; 295(6): R1730 - R1736. [Abstract] [Full Text] [PDF]

				G. Paz-Filho, K. Esposito, B. Hurwitz, A. Sharma, C. Dong, V. Andreev, T. Delibasi, H. Erol, A. Ayala, M.-L. Wong, et al. Changes in insulin sensitivity during leptin replacement therapy in leptin-deficient patients Am J Physiol Endocrinol Metab, December 1, 2008; 295(6): E1401 - E1408. [Abstract] [Full Text] [PDF]

				S. Park, B. J. Bivona, Y. Feng, E. Lazartigues, and L. M. Harrison-Bernard Intact renal afferent arteriolar autoregulatory responsiveness in db/db mice Am J Physiol Renal Physiol, November 1, 2008; 295(5): F1504 - F1511. [Abstract] [Full Text] [PDF]

				S. S. Martin, A. Qasim, and M. P. Reilly Leptin Resistance: A Possible Interface of Inflammation and Metabolism in Obesity-Related Cardiovascular Disease J. Am. Coll. Cardiol., October 7, 2008; 52(15): 1201 - 1210. [Abstract] [Full Text] [PDF]

				G. Matarese, C. Procaccini, and V. De Rosa The intricate interface between immune and metabolic regulation: a role for leptin in the pathogenesis of multiple sclerosis? J. Leukoc. Biol., October 1, 2008; 84(4): 893 - 899. [Abstract] [Full Text] [PDF]

				N. J. MacIver, S. R. Jacobs, H. L. Wieman, J. A. Wofford, J. L. Coloff, and J. C. Rathmell Glucose metabolism in lymphocytes is a regulated process with significant effects on immune cell function and survival J. Leukoc. Biol., October 1, 2008; 84(4): 949 - 957. [Abstract] [Full Text] [PDF]

				J. L. Chan, C. J. Williams, P. Raciti, J. Blakeman, T. Kelesidis, I. Kelesidis, M. L. Johnson, M. O. Thorner, and C. S. Mantzoros Leptin Does Not Mediate Short-Term Fasting-Induced Changes in Growth Hormone Pulsatility but Increases IGF-I in Leptin Deficiency States J. Clin. Endocrinol. Metab., July 1, 2008; 93(7): 2819 - 2827. [Abstract] [Full Text] [PDF]

				V. E F Crowley Overview of human obesity and central mechanisms regulating energy homeostasis Ann Clin Biochem, May 1, 2008; 45(3): 245 - 255. [Abstract] [Full Text] [PDF]

				P. Kumpers, R. Horn, G. Brabant, A. Woywodt, M. Schiffer, H. Haller, and M. Haubitz Serum leptin and ghrelin correlate with disease activity in ANCA-associated vasculitis Rheumatology, April 1, 2008; 47(4): 484 - 487. [Abstract] [Full Text] [PDF]

				K. Baicy, E. D. London, J. Monterosso, M.-L. Wong, T. Delibasi, A. Sharma, and J. Licinio From the Cover: Leptin replacement alters brain response to food cues in genetically leptin-deficient adults PNAS, November 13, 2007; 104(46): 18276 - 18279. [Abstract] [Full Text] [PDF]

				M. S. Desruisseaux, Nagajyothi, M. E. Trujillo, H. B. Tanowitz, and P. E. Scherer Adipocyte, Adipose Tissue, and Infectious Disease Infect. Immun., March 1, 2007; 75(3): 1066 - 1078. [Full Text] [PDF]

				I. S. Farooqi, T. Wangensteen, S. Collins, W. Kimber, G. Matarese, J. M. Keogh, E. Lank, B. Bottomley, J. Lopez-Fernandez, I. Ferraz-Amaro, et al. Clinical and Molecular Genetic Spectrum of Congenital Deficiency of the Leptin Receptor N. Engl. J. Med., January 18, 2007; 356(3): 237 - 247. [Abstract] [Full Text] [PDF]

				I. S. Farooqi and S. O'Rahilly Genetics of Obesity in Humans Endocr. Rev., December 1, 2006; 27(7): 710 - 718. [Abstract] [Full Text] [PDF]

				N. Stefanou, M. Satra, V. Papanikolaou, F. Kalala, N. Gatselis, A. Germenis, G. N. Dalekos, and A. Tsezou Leptin receptor isoforms mRNA expression in peripheral blood mononuclear cells from patients with chronic viral hepatitis. Experimental Biology and Medicine, November 1, 2006; 231(10): 1653 - 1663. [Abstract] [Full Text] [PDF]

				G. Palmer, M. Aurrand-Lions, E. Contassot, D. Talabot-Ayer, D. Ducrest-Gay, C. Vesin, V. Chobaz-Peclat, N. Busso, and C. Gabay Indirect Effects of Leptin Receptor Deficiency on Lymphocyte Populations and Immune Response in db/db Mice. J. Immunol., September 1, 2006; 177(5): 2899 - 2907. [Abstract] [Full Text] [PDF]

				M. Otero, R. Lago, R. Gomez, C. Dieguez, F. Lago, J. Gomez-Reino, and O. Gualillo Towards a pro-inflammatory and immunomodulatory emerging role of leptin Rheumatology, August 1, 2006; 45(8): 944 - 950. [Abstract] [Full Text] [PDF]

				S. O'Rahilly and I.S. Farooqi Genetics of obesity Phil Trans R Soc B, July 29, 2006; 361(1471): 1095 - 1105. [Abstract] [Full Text] [PDF]

				J. L. Chan, G. Matarese, G. K. Shetty, P. Raciti, I. Kelesidis, D. Aufiero, V. De Rosa, F. Perna, S. Fontana, and C. S. Mantzoros Differential regulation of metabolic, neuroendocrine, and immune function by leptin in humans PNAS, May 30, 2006; 103(22): 8481 - 8486. [Abstract] [Full Text] [PDF]

				E. A. Oral, E. D. Javor, L. Ding, G. Uzel, E. K. Cochran, J. R. Young, A. M. DePaoli, S. M. Holland, and P. Gorden Leptin Replacement Therapy Modulates Circulating Lymphocyte Subsets and Cytokine Responsiveness in Severe Lipodystrophy J. Clin. Endocrinol. Metab., February 1, 2006; 91(2): 621 - 628. [Abstract] [Full Text] [PDF]

				C. W. Wieland, S. Florquin, E. D. Chan, J. C. Leemans, S. Weijer, A. Verbon, G. Fantuzzi, and T. van der Poll Pulmonary Mycobacterium tuberculosis infection in leptin-deficient ob/ob mice Int. Immunol., November 1, 2005; 17(11): 1399 - 1408. [Abstract] [Full Text] [PDF]

				A. Bruno, P. Chanez, G. Chiappara, L. Siena, S. Giammanco, M. Gjomarkaj, G. Bonsignore, J. Bousquet, and A. M. Vignola Does leptin play a cytokine-like role within the airways of COPD patients? Eur. Respir. J., September 1, 2005; 26(3): 398 - 405. [Abstract] [Full Text] [PDF]

				C Popa, M G Netea, T R D S Radstake, P L van Riel, P Barrera, and J W M van der Meer Markers of inflammation are negatively correlated with serum leptin in rheumatoid arthritis Ann Rheum Dis, August 1, 2005; 64(8): 1195 - 1198. [Abstract] [Full Text] [PDF]

				L. S. Tallam, D. E. Stec, M. A. Willis, A. A. da Silva, and J. E. Hall Melanocortin-4 Receptor-Deficient Mice Are Not Hypertensive or Salt-Sensitive Despite Obesity, Hyperinsulinemia, and Hyperleptinemia Hypertension, August 1, 2005; 46(2): 326 - 332. [Abstract] [Full Text] [PDF]

				M. Banning Obesity: pathophysiology and treatment Perspectives in Public Health, July 1, 2005; 125(4): 163 - 167. [Abstract] [PDF]

				B. Mattioli, E. Straface, M. G. Quaranta, L. Giordani, and M. Viora Leptin Promotes Differentiation and Survival of Human Dendritic Cells and Licenses Them for Th1 Priming J. Immunol., June 1, 2005; 174(11): 6820 - 6828. [Abstract] [Full Text] [PDF]

				M. M. Grumbach A Window of Opportunity: The Diagnosis of Gonadotropin Deficiency in the Male Infant J. Clin. Endocrinol. Metab., May 1, 2005; 90(5): 3122 - 3127. [Abstract] [Full Text] [PDF]

				G. Matarese, S. Moschos, and C. S. Mantzoros Leptin in Immunology J. Immunol., March 15, 2005; 174(6): 3137 - 3142. [Abstract] [Full Text] [PDF]

				J. L. Chan, S. J. Moschos, J. Bullen, K. Heist, X. Li, Y.-B. Kim, B. B. Kahn, and C. S. Mantzoros Recombinant Methionyl Human Leptin Administration Activates Signal Transducer and Activator of Transcription 3 Signaling in Peripheral Blood Mononuclear Cells in Vivo and Regulates Soluble Tumor Necrosis Factor-{alpha} Receptor Levels in Humans with Relative Leptin Deficiency J. Clin. Endocrinol. Metab., March 1, 2005; 90(3): 1625 - 1631. [Abstract] [Full Text] [PDF]

				M. Cote, P. Mauriege, J. Bergeron, N. Almeras, A. Tremblay, I. Lemieux, and J.-P. Despres Adiponectinemia in Visceral Obesity: Impact on Glucose Tolerance and Plasma Lipoprotein and Lipid Levels in Men J. Clin. Endocrinol. Metab., March 1, 2005; 90(3): 1434 - 1439. [Abstract] [Full Text] [PDF]

				W. T. Gibson, I. S. Farooqi, M. Moreau, A. M. DePaoli, E. Lawrence, S. O'Rahilly, and R. A. Trussell Congenital Leptin Deficiency Due to Homozygosity for the {Delta}133G Mutation: Report of Another Case and Evaluation of Response to Four Years of Leptin Therapy J. Clin. Endocrinol. Metab., October 1, 2004; 89(10): 4821 - 4826. [Abstract] [Full Text] [PDF]

				S. Bluher and C. S. Mantzoros The Role of Leptin in Regulating Neuroendocrine Function in Humans J. Nutr., September 1, 2004; 134(9): 2469S - 2474S. [Abstract] [Full Text] [PDF]

				S. Ten and N. Maclaren Insulin Resistance Syndrome in Children J. Clin. Endocrinol. Metab., June 1, 2004; 89(6): 2526 - 2539. [Abstract] [Full Text] [PDF]

				J. Licinio, S. Caglayan, M. Ozata, B. O. Yildiz, P. B. de Miranda, F. O'Kirwan, R. Whitby, L. Liang, P. Cohen, S. Bhasin, et al. Phenotypic effects of leptin replacement on morbid obesity, diabetes mellitus, hypogonadism, and behavior in leptin-deficient adults PNAS, March 30, 2004; 101(13): 4531 - 4536. [Abstract] [Full Text] [PDF]

				D. V. Tortoriello, J. McMinn, and S. C. Chua Dietary-Induced Obesity and Hypothalamic Infertility in Female DBA/2J Mice Endocrinology, March 1, 2004; 145(3): 1238 - 1247. [Abstract] [Full Text] [PDF]

				H. Zarkesh-Esfahani, A. G. Pockley, Z. Wu, P. G. Hellewell, A. P. Weetman, and R. J. M. Ross Leptin Indirectly Activates Human Neutrophils via Induction of TNF-{alpha} J. Immunol., February 1, 2004; 172(3): 1809 - 1814. [Abstract] [Full Text] [PDF]

				M.-L. Wong, J. Licinio, B. O. Yildiz, C. S. Mantzoros, P. Prolo, M. Kling, and P. W. Gold Simultaneous and Continuous 24-Hour Plasma and Cerebrospinal Fluid Leptin Measurements: Dissociation of Concentrations in Central and Peripheral Compartments J. Clin. Endocrinol. Metab., January 1, 2004; 89(1): 258 - 265. [Abstract] [Full Text] [PDF]

				I.S. Farooqi and S. O'Rahilly Monogenic Human Obesity Syndromes Recent Prog. Horm. Res., January 1, 2004; 59(1): 409 - 424. [Abstract] [Full Text]

				T. M. Plant and M. L. Barker-Gibb Neurobiological mechanisms of puberty in higher primates Hum. Reprod. Update, January 1, 2004; 10(1): 67 - 77. [Abstract] [Full Text] [PDF]

				G. R. Steinberg, A. C. Smith, S. Wormald, P. Malenfant, C. Collier, and D. J. Dyck Endurance training partially reverses dietary-induced leptin resistance in rodent skeletal muscle Am J Physiol Endocrinol Metab, January 1, 2004; 286(1): E57 - E63. [Abstract] [Full Text] [PDF]

				A. Ghazali, F. Grados, R. Oprisiu, D. Bunea, P. Moriniere, N. El Esper, I. El Esper, M. Brazier, J. C. Souberbielle, A. Fournier, et al. Bone mineral density directly correlates with elevated serum leptin in haemodialysis patients Nephrol. Dial. Transplant., September 1, 2003; 18(9): 1882 - 1890. [Abstract] [Full Text] [PDF]

				S. O'Rahilly, I. S. Farooqi, G. S. H. Yeo, and B. G. Challis Minireview: Human Obesity--Lessons from Monogenic Disorders Endocrinology, September 1, 2003; 144(9): 3757 - 3764. [Abstract] [Full Text] [PDF]

				C. J Hukshorn, M. S Westerterp-Plantenga, and W. H. Saris Pegylated human recombinant leptin (PEG-OB) causes additional weight loss in severely energy-restricted, overweight men Am. J. Clinical Nutrition, April 1, 2003; 77(4): 771 - 776. [Abstract] [Full Text] [PDF]

				M. Ozata, C. Dieguez, and F. F. Casanueva The Inhibition of Growth Hormone Secretion Presented in Obesity Is Not Mediated by the High Leptin Levels: A Study in Human Leptin Deficiency Patients J. Clin. Endocrinol. Metab., January 1, 2003; 88(1): 312 - 316. [Abstract] [Full Text] [PDF]

				M Labib The investigation and management of obesity J. Clin. Pathol., January 1, 2003; 56(1): 17 - 25. [Abstract] [Full Text] [PDF]

				M. L. Barker-Gibb, A. Sahu, C. R. Pohl, and T. M. Plant Elevating Circulating Leptin in Prepubertal Male Rhesus Monkeys (Macaca mulatta) Does Not Elicit Precocious Gonadotropin-Releasing Hormone Release, Assessed Indirectly J. Clin. Endocrinol. Metab., November 1, 2002; 87(11): 4976 - 4983. [Abstract] [Full Text] [PDF]

				G. Kilciler, M. Ozata, C. Oktenli, S.Y. Sanisoglu, E. Bolu, N. Bingol, M. Kilciler, I. C. Ozdemir, and M. Kutlu Diurnal Leptin Secretion Is Intact in Male Hypogonadotropic Hypogonadism and Is Not Influenced by Exogenous Gonadotropins J. Clin. Endocrinol. Metab., November 1, 2002; 87(11): 5023 - 5029. [Abstract] [Full Text] [PDF]

				S E Moore, G Morgan, A C Collinson, J A Swain, M A O'Connell, and A M Prentice Leptin, malnutrition, and immune response in rural Gambian children Arch. Dis. Child., September 1, 2002; 87(3): 192 - 197. [Abstract] [Full Text] [PDF]

				G. M. Lord, G. Matarese, J. K. Howard, S. R. Bloom, and R. I. Lechler Leptin inhibits the anti-CD3-driven proliferation of peripheral blood T cells but enhances the production of proinflammatory cytokines J. Leukoc. Biol., August 1, 2002; 72(2): 330 - 338. [Abstract] [Full Text] [PDF]

				A. Garg and A. Misra Hepatic Steatosis, Insulin Resistance, and Adipose Tissue Disorders J. Clin. Endocrinol. Metab., July 1, 2002; 87(7): 3019 - 3022. [Full Text] [PDF]

				C. Grunfeld Leptin and the Immunosuppression of Malnutrition J. Clin. Endocrinol. Metab., July 1, 2002; 87(7): 3038 - 3039. [Full Text] [PDF]

				E. A. Oral, E. Ruiz, A. Andewelt, N. Sebring, A. J. Wagner, A. M. Depaoli, and P. Gorden Effect of Leptin Replacement on Pituitary Hormone Regulation in Patients with Severe Lipodystrophy J. Clin. Endocrinol. Metab., July 1, 2002; 87(7): 3110 - 3117. [Abstract] [Full Text] [PDF]

				H. Blain, A. Vuillemin, F. Guillemin, R. Durant, B. Hanesse, N. de Talance, B. Doucet, and C. Jeandel Serum Leptin Level Is a Predictor of Bone Mineral Density in Postmenopausal Women J. Clin. Endocrinol. Metab., March 1, 2002; 87(3): 1030 - 1035. [Abstract] [Full Text] [PDF]

				M. Ozata, C. Oktenli, M. Gulec, T. Ozgurtas, F. Bulucu, K. Caglar, N. Bingol, A. Vural, and I. C. Ozdemir Increased Fasting Plasma Acylation-Stimulating Protein Concentrations in Nephrotic Syndrome J. Clin. Endocrinol. Metab., February 1, 2002; 87(2): 853 - 858. [Abstract] [Full Text] [PDF]

				M. Ozata Different Presentation of Bone Mass in Mice and Humans with Congenital Leptin Deficiency J. Clin. Endocrinol. Metab., February 1, 2002; 87(2): 951 - 951. [Full Text]

				N. Busso, A. So, V. Chobaz-Peclat, C. Morard, E. Martinez-Soria, D. Talabot-Ayer, and C. Gabay Leptin Signaling Deficiency Impairs Humoral and Cellular Immune Responses and Attenuates Experimental Arthritis J. Immunol., January 15, 2002; 168(2): 875 - 882. [Abstract] [Full Text] [PDF]

				R. FAGGIONI, K. R. FEINGOLD, and C. GRUNFELD Leptin regulation of the immune response and the immunodeficiency of malnutrition FASEB J, December 1, 2001; 15(14): 2565 - 2571. [Abstract] [Full Text] [PDF]

				G. FRUHBECK and J. GOMEZ-AMBROSI Rationale for the existence of additional adipostatic hormones FASEB J, September 1, 2001; 15(11): 1996 - 2006. [Abstract] [Full Text] [PDF]

				M. L.G. Correia, D. A. Morgan, J. L. Mitchell, W. I. Sivitz, A. L. Mark, and W. G. Haynes Role of Corticotrophin-Releasing Factor in Effects of Leptin on Sympathetic Nerve Activity and Arterial Pressure Hypertension, September 1, 2001; 38(3): 384 - 388. [Abstract] [Full Text] [PDF]

				M. Ozata, D. Gungor, M. Turan, G. Ozisik, N. Bingol, T. Ozgurtas, and I. C. Ozdemir Improved Glycemic Control Increases Fasting Plasma Acylation-Stimulating Protein and Decreases Leptin Concentrations in Type II Diabetic Subjects J. Clin. Endocrinol. Metab., August 1, 2001; 86(8): 3659 - 3664. [Abstract] [Full Text] [PDF]

				W.-S. Yang, W.-J. Lee, T. Funahashi, S. Tanaka, Y. Matsuzawa, C.-L. Chao, C.-L. Chen, T.-Y. Tai, and L.-M. Chuang Weight Reduction Increases Plasma Levels of an Adipose-Derived Anti-Inflammatory Protein, Adiponectin J. Clin. Endocrinol. Metab., August 1, 2001; 86(8): 3815 - 3819. [Abstract] [Full Text] [PDF]

				B. Burguera, L. C. Hofbauer, T. Thomas, F. Gori, G. L. Evans, S. Khosla, B. L. Riggs, and R. T. Turner Leptin Reduces Ovariectomy-Induced Bone Loss in Rats Endocrinology, August 1, 2001; 142(8): 3546 - 3553. [Abstract] [Full Text] [PDF]

				C. S. Mantzoros, M. Ozata, A. B. Negrao, M. A. Suchard, M. Ziotopoulou, S. Caglayan, R. M. Elashoff, R. J. Cogswell, P. Negro, V. Liberty, et al. Synchronicity of Frequently Sampled Thyrotropin (TSH) and Leptin Concentrations in Healthy Adults and Leptin-Deficient Subjects: Evidence for Possible Partial TSH Regulation by Leptin in Humans J. Clin. Endocrinol. Metab., July 1, 2001; 86(7): 3284 - 3291. [Abstract] [Full Text] [PDF]

				A. Sonmez, U. Kisa, G. Uckaya, T. Eyileten, B. Comert, B. Koc, F. Kocabalkan, and M. Ozata Effects of losartan treatment on T-cell activities and plasma leptin concentrations in primary hypertension Journal of Renin-Angiotensin-Aldosterone System, June 1, 2001; 2(2): 112 - 116. [Abstract] [PDF]

				L. Ghizzoni, G. Mastorakos, M. Ziveri, M. Furlini, A. Solazzi, A. Vottero, and S. Bernasconi Interactions of Leptin and Thyrotropin 24-Hour Secretory Profiles in Short Normal Children J. Clin. Endocrinol. Metab., May 1, 2001; 86(5): 2065 - 2072. [Abstract] [Full Text]

				G. Fantuzzi and R. Faggioni Leptin in the regulation of immunity, inflammation, and hematopoiesis J. Leukoc. Biol., October 1, 2000; 68(4): 437 - 446. [Abstract] [Full Text]

				A. M. Rice, J. N. Fain, and S. A. Rivkees A1 Adenosine Receptor Activation Increases Adipocyte Leptin Secretion Endocrinology, April 1, 2000; 141(4): 1442 - 1445. [Abstract] [Full Text] [PDF]