ORCID Profile
0000-0002-5780-8209
Current Organisations
Vienna School of Clinical Research, Good Clinical Practice Course
,
Good Clinical Practice Course
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Publications
Congenital leptin deficiency: Diagnosis and effects of leptin replacement therapy,Deficiência congênita de leptina: Diagnóstico e efeitos da terapia de reposição
Publisher: FapUNIFESP (SciELO)
Date: 11-2010
DOI: 10.1590/S0004-27302010000800005
Abstract: To describe our 10-year experience in treating leptin-deficient humans. Three adults and one boy presented with childhood-onset morbid obesity, hypogonadism and family history of obesity and early death. Serum leptin was inappropriately low. A recessive C105T leptin gene mutation was identified. Metabolic and endocrine assessments were conducted, before and while on and off leptin. The adults' body mass index decreased from 51.2 ± 2.5 to 29.5 ± 2.8 kg/m². Serum lipids normalized, insulin resistance decreased, and one of the initially diabetic females became normoglycemic. Hypogonadotropic hypogonadism was reversed, and other changes were observed in the adrenal, sympathetic, somatotropic and thyroid functions. Leptin replacement therapy reverses endocrine and metabolic alterations associated with leptin deficiency. Some of these results may be extrapolated to other diseases.
Short-Term Plasticity of Gray Matter Associated with Leptin Deficiency and Replacement
Publisher: The Endocrine Society
Date: 08-2011
DOI: 10.1210/JC.2011-0314
Leptin and insulin sensitivity: reply to Oral and Burant
Publisher: American Physiological Society
Date: 02-2009
Effects of leptin on intake of specific micro- and macronutrients in a woman with leptin gene deficiency studied off and on leptin at stable body weight
Publisher: Elsevier BV
Date: 11-2007
Effects of Leptin Replacement on Risk Factors for Cardiovascular Disease in Genetically Leptin-deficient Subjects
Publisher: Georg Thieme Verlag KG
Date: 22-08-2008
Leptin replacement alters brain response to food cues in genetically leptin-deficient adults
Publisher: Proceedings of the National Academy of Sciences
Date: 13-11-2007
Abstract: A missense mutation in the ob gene causes leptin deficiency and morbid obesity. Leptin replacement to three adults with this mutation normalized body weight and eating behavior. Because the neural circuits mediating these changes were unknown, we paired functional magnetic resonance imaging (fMRI) with presentation of food cues to these subjects. During viewing of food-related stimuli, leptin replacement reduced brain activation in regions linked to hunger (insula, parietal and temporal cortex) while enhancing activation in regions linked to inhibition and satiety (prefrontal cortex). Leptin appears to modulate feeding behavior through these circuits, suggesting therapeutic targets for human obesity.
Effects of Leptin on Lipid Metabolism
Publisher: Georg Thieme Verlag KG
Date: 08-2008
Congenital leptin deficiency and thyroid function
Publisher: Springer Science and Business Media LLC
Date: 04-11-2009
Abstract: Thyroid function is closely related to leptin's secretion by the adipose tissue. In states of leptin-deficiency, the circadian rhythm of TSH is altered, leading to central hypothyroidism in animal models. In humans, central hypothyroidism has also been described in rare cases of congenital leptin deficiency. However, the thyroid phenotype in these cases is heterogeneous, with the occurrence of central hypothyroidism in a minority of cases. Here we describe thyroid function in four leptin-deficient humans (2 males aged 5 and 27, and 2 females aged 35 and 40), before and during leptin replacement with recombinant human methionyl leptin (r-metHuLeptin). The child was evaluated for four years, and the adults, for eight years. In addition, the adults were submitted to a brief withdrawal of leptin during six weeks in the sixth year. Our results show that, regardless of leptin replacement, our leptin-deficient patients have normal thyroid function. In spite of having an important role in regulating the hypothalamic-pituitary-thyroidal axis, leptin is not required for normal thyroid function. Trial Registration ClinicalTrials.gov Identifiers: NCT00659828 and NCT00657605
Changes in insulin sensitivity during leptin replacement therapy in leptin-deficient patients
Publisher: American Physiological Society
Date: 12-2008
DOI: 10.1152/AJPENDO.90450.2008
Abstract: Leptin replacement rescues the phenotype of morbid obesity and hypogonadism in leptin-deficient adults. However, leptin's effects on insulin resistance are not well understood. Our objective was to evaluate the effects of leptin on insulin resistance. Three leptin-deficient adults (male, 32 yr old, BMI 23.5 kg/m 2 female, 42 yr old, BMI 25.1 kg/m 2 female, 46 yr old, BMI 31.7 kg/m 2 ) with a missense mutation of the leptin gene were evaluated during treatment with recombinant methionyl human leptin (r-metHuLeptin). Insulin resistance was determined by euglycemic hyperinsulinemic cl s and by oral glucose tolerance tests (OGTTs), whereas patients were on r-metHuLeptin and after treatment was interrupted for 2–4 wk in the 4th, 5th, and 6th years of treatment. At baseline, all patients had normal insulin levels, C-peptide, and homeostatic model assessment of insulin resistance index, except for one female diagnosed with type 2 diabetes. The glucose infusion rate was significantly lower with r-metHuLeptin (12.03 ± 3.27 vs. 8.16 ± 2.77 mg·kg −1 ·min −1 , P = 0.0016) but did not differ in the 4th, 5th, and 6th years of treatment when all results were analyzed by a mixed model [ F( 1 , 4 ) = 0.57 and P = 0.5951]. The female patient with type 2 diabetes became euglycemic after treatment with r-metHuLeptin and subsequent weight loss. The OGTT suggested that two patients showed decreased insulin resistance while off treatment. During an off-leptin OGTT, one of the patients developed a moderate hypoglycemic reaction attributed to increased posthepatic insulin delivery and sensitivity. We conclude that, in leptin-deficient adults, the interruption of r-metHuLeptin decreases insulin resistance in the context of rapid weight gain. Our results suggest that hyperleptinemia may contribute to mediate the increased insulin resistance of obesity.
Cellular Immunity Before and After Leptin Replacement Therapy
Publisher: Walter de Gruyter GmbH
Date: 2009
DOI: 10.1515/JPEM.2009.22.11.1069
Abstract: The few identified leptin-deficient children have immune deficiency. To evaluate whether a newly-identified leptin-deficient boy has immune defects to assess the immune changes during leptin replacement. A 5 year-old boy with congenital leptin deficiency was evaluated before, 2 weeks and 6 weeks after the initiation of recombinant methionyl human leptin. Thymic volume was measured by computed tomography. Humoral immunity was assessed by measuring levels of several immunoglobulins. Cellular immunity was evaluated by the analysis of lymphocyte proliferation in response to mitogens. Lymphocyte subsets were quantified by flow cytometry. At baseline, thymic volume was increased. The lymphocyte subsets count and humoral/cellular immunities were normal. After treatment, proliferative response to mitogens increased by 1.5- to 3-fold, and lymphocyte count decreased by 17%. Immune defects are not an obligatory feature of congenital leptin deficiency. Even in the absence of significant immune defects, leptin replacement therapy enhanced T-cell responsiveness.
Effects of leptin replacement on macro- and micronutrient preferences
Publisher: Springer Science and Business Media LLC
Date: 07-08-2007
Abstract: The mechanisms underlying food choices are complex and involve neuroendocrine and biochemical signaling. Among neuroendocrine signals, leptin may play a prominent role in food preference. This study was designed to obtain an understanding of the effects of leptin replacement on macro- and micronutrient preferences in leptin-deficient adults. We studied the effects of leptin replacement on three adults with genetic leptin deficiency during the initial 12 months of treatment. Dietary intake was measured in our study by weighed food consumption records. Nutrient intake was calculated using a nutrition analysis software. After leptin replacement was started, all patients had initially a marked reduction in food intake. The reduction in caloric intake differentially affected intake of macro- and micronutrients. There was an initial shift toward a higher percentage consumption of fats and a decrease in the intake of carbohydrates. Significant differences also occurred in 7 distinct types of macronutrients, 12 vitamins, 11 minerals and 1 amino acid. We documented several specific leptin-induced changes in macro- and micronutrients intake during the course of leptin-replacement treatment, the majority of which were not related to the decrease in total caloric consumption.
Related Organisations
Vienna School Of Clinical Research, Good Clinical Practice Course
Location: Turkey
Related Funding Activities
No related grants have been discovered for Tuncay Delibasi.