ORCID Profile
0000-0001-5760-4276
Current Organisations
Tulane University
,
University of Arizona
,
Docus Telemedicine Platform
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Publisher: The Endocrine Society
Date: 08-2011
DOI: 10.1210/JC.2011-0314
Publisher: Georg Thieme Verlag KG
Date: 22-08-2008
Publisher: Public Library of Science (PLoS)
Date: 29-08-2008
Publisher: Georg Thieme Verlag KG
Date: 08-2008
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
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.
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.
No related grants have been discovered for Halil Kutlu Erol.