The Effects of Leptin Replacement on Neural Plasticity

Leptin, an adipokine synthesized and secreted mainly by the adipose tissue, has multiple effects on the regulation of food intake, energy expenditure, and metabolism. Its recently-approved analogue, metreleptin, has been evaluated in clinical trials for the treatment of patients with leptin deficiency due to mutations in the leptin gene, lipodystrophy syndromes, and hypothalamic amenorrhea. In such patients, leptin replacement therapy has led to changes in brain structure and function in intra- and extrahypothalamic areas, including the hippocampus. Furthermore, in one of those patients, improvements in neurocognitive development have been observed. In addition to this evidence linking leptin to neural plasticity and function, observational studies evaluating leptin-sufficient humans have also demonstrated direct correlation between blood leptin levels and brain volume and inverse associations between circulating leptin and risk for the development of dementia. This review summarizes the evidence in the literature on the role of leptin in neural plasticity (in leptin-deficient and in leptin-sufficient individuals) and its effects on synaptic activity, glutamate receptor trafficking, neuronal morphology, neuronal development and survival, and microglial functio

Neuroendokrynna regulacja masy ciała: integracja tkanki tłuszczowej, układu pokarmowego i mózgu

Human body weight is maintained at a fairly stable level regardless of changes in energy intake and energy expenditure. Compensatory mechanisms within the central nervous system (CNS), which regulate food intake and energy expenditure, are triggered by other central and peripheral signals. Peripherally, the main sources of those signals are the adipose tissue, gastrointestinal tract, and pancreas. The main signal originating from the adipose tissue is leptin, which promotes the activation of anorexigenic pathways in the CNS. Similarly, the central action of insulin also reduces food intake and stimulates catabolic pathways. The gastrointestinal tract contributes with several peptides that influence food intake, such as ghrelin, glucagon-like peptide 1 (GLP-1), peptide YY (PYY), oxyntomodulin (OXM), and cholecystokinin (CCK). Other substances secreted by the pancreas, such as pancreatic polypeptide (PP) and amylin, a hormone co-secreted with insulin, also affect energy balance. More recently, the endocannabinoid system has also been identified as a contributor in the maintenance of energy balance. Better understanding of these mechanistic systems involved in the regulation of energy metabolism will hopefully lead to the development of new therapeutic approaches against obesity, metabolic syndrome, and other nutritional disorders. (Pol J Endocrinol 2010; 61 (2): 194-206)Masa ciała człowieka jest utrzymywana na względnie stałym poziomie niezależnie od zmian zarówno w dostarczaniu energii, jak i jej zużywania. Mechanizm kompensacyjny w ośrodkowym układzie nerwowym (CNS, central nervous system [OUN]), który reguluje przyjmowanie pokarmu i wydatek energii jest uruchamiany przez inne sygnały ośrodkowe i obwodowe. Obwodowo, źródłem tych sygnałów jest tkanka tłuszczowa, układ pokarmowy i trzustka. Głównym sygnałem pochodzącym z tkanki tuszczowej jest leptyna, która powoduje aktywację anoreksogennych dróg przekazu sygnału w CNS. Podobnie, oddziaływanie ośrodkowe insuliny także zmniejsza przyjmowanie pokarmu i stymuluje kataboliczne drogi przekazu sygnału. W układzie pokarmowym współdziała kilka peptydów, które wpływają na przyjmowanie pokarmu, takie jak grelina, peptyd podobny do glukagonu (GLP-1, glucagon-like peptide), peptyd YY (PYY, peptide YY), oksyntomodulina (OXM, oxyntomodulin) i cholecystokinina (CCK, cholecystokinin), Pozostałe substancje wydzielane przez trzustkę, takie jak polipeptyd trzustkowy (PP, pancreatic polypeptide) i amylina, hormon wydzielany jednocześnie z insuliną , także wpływają na równowagę energetyczną. W najnowszych badaniach stwierdzono, że układ endokannabinoidowy przyczynia sie do zachowania równowagi energetycznej. Lepsze zrozumienie mechanizmów układów wpływających na regulacje przemiany energii przyczyni się do rozwoju nowych terapii otyłości, zespołu metabolicznego i innych zaburzeń odżywiania. (Endokrynol Pol 2010; 61 (2): 194-206

Uso do TSH recombinante humano em dose baixa e única (0,1 mg) associado à atividade ambulatorial (30 mCi) de radioiodo no tratamento do bócio multinodular /

Orientador: Hans GrafDissertação (mestrado) - Universidade Federal do Paraná, Setor de Ciências da Saúde, Programa de Pós-Graduação em Medicina Interna. Defesa: Curitiba, 2006Inclui bibliografia e anexo

The use of dried blood spot sampling for the measurement of HbA1c: a cross-sectional study

BACKGROUND: The use of dried blood spot (DBS) sampling is an alternative to traditional venous blood collection, and particularly useful for people living in rural and remote areas, and for those who are infirm, house-bound or time-poor. The objective of this study was to assess whether the measurement of glycated haemoglobin A1c (HbA1c) in DBS samples provided comparative and acceptably precise results. METHODS: Venous and capillary blood samples were collected from 115 adult participants. After proper instruction, each participant punctured his/her own finger and collected capillary blood samples on pieces of a proprietary cellulose filter paper. Each filter paper was subsequently placed inside a breathable envelope, stored at room temperature, and processed on the same day (D0), four (D4), seven (D7) and fourteen (D14) days after collection. HbA1c was measured in duplicates/triplicates in whole venous blood (WB), capillary blood (capDBS) and venous blood placed on the matrix paper (venDBS), by turbidimetric inhibition immunoassay. Intra-assay coefficients of variation (CV) were calculated. DBS values were compared to WB results using linear regression, Bland-Altman plots and cross-validation models. RESULTS: Eleven and 56 patients had type 1 and type 2 diabetes mellitus, respectively. Mean HbA1c levels were 6.22 ± 1.11 % for WB samples (n = 115). The median intra-assay CV was lower than 3 % for WB and capDBS on all days. Results from capDBS and venDBS showed high correlation and agreement to WB results, with narrow 95 % limits of agreement (except for results from D14 samples), as observed in Bland-Altman plots. When capDBS values were applied to equations derived from regression analyses, results approached those of WB values. A cross-validation model showed that capDBS results on D0, D4 and D7 were close to the WB results, with prediction intervals that were narrow enough to be clinically acceptable. CONCLUSIONS: The measurement of HbA1c from DBS samples provided results that were comparable to results from WB samples, if measured up to seven days after collection. Intra-assay coefficients of variation were low, results were in agreement with the gold-standard, and prediction intervals were clinically acceptable. The measurement of HbA1c through DBS sampling may be considered in situations where traditional venipuncture is not available.This study was funded by MyHealthTest Pty, including the article-processing charge

Is increased antidepressant exposure a contributory factor to the obesity pandemic?

This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article's Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/Major depressive disorder (MDD) and obesity are both common heterogeneous disorders with complex aetiology, with a major impact on public health. Antidepressant prescribing has risen nearly 400% since 1988, according to data from the Centers for Disease Control and Prevention (CDC). In parallel, adult obesity rates have doubled since 1980, from 15 to 30 percent, while childhood obesity rates have more than tripled. Rising obesity rates have significant health consequences, contributing to increased rates of more than thirty serious diseases. Despite the concomitant rise of antidepressant use and of the obesity rates in Western societies, the association between the two, as well as the mechanisms underlying antidepressant-induced weight gain, remain under explored. In this review, we highlight the complex relationship between antidepressant use, MDD and weight gain. Clinical findings have suggested that obesity may increase the risk of developing MDD, and vice versa. Hypothalamic–pituitary–adrenal (HPA) axis activation occurs in the state of stress; concurrently, the HPA axis is also dysregulated in obesity and metabolic syndrome, making it the most well-understood shared common pathophysiological pathway with MDD. Numerous studies have investigated the effects of different classes of antidepressants on body weight. Previous clinical studies suggest that the tricyclics amitriptyline, nortriptyline and imipramine, and the serotonin norepinephrine reuptake inhibitor mirtazapine are associated with weight gain. Despite the fact that selective serotonin reuptake inhibitor (SSRI) use has been associated with weight loss during acute treatment, a number of studies have shown that SSRIs may be associated with long-term risk of weight gain; however, because of high variability and multiple confounds in clinical studies, the long-term effect of SSRI treatment and SSRI exposure on body weight remains unclear. A recently developed animal paradigm shows that the combination of stress and antidepressants followed by long-term high-fat diet results, long after discontinuation of antidepressant treatment, in markedly increased weight, in excess of what is caused by high-fat diet alone. On the basis of existing epidemiological, clinical and preclinical data, we have generated the testable hypothesis that escalatin

Is increased antidepressant exposure a contributory factor to the obesity pandemic?

This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article's Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/Major depressive disorder (MDD) and obesity are both common heterogeneous disorders with complex aetiology, with a major impact on public health. Antidepressant prescribing has risen nearly 400% since 1988, according to data from the Centers for Disease Control and Prevention (CDC). In parallel, adult obesity rates have doubled since 1980, from 15 to 30 percent, while childhood obesity rates have more than tripled. Rising obesity rates have significant health consequences, contributing to increased rates of more than thirty serious diseases. Despite the concomitant rise of antidepressant use and of the obesity rates in Western societies, the association between the two, as well as the mechanisms underlying antidepressant-induced weight gain, remain under explored. In this review, we highlight the complex relationship between antidepressant use, MDD and weight gain. Clinical findings have suggested that obesity may increase the risk of developing MDD, and vice versa. Hypothalamic–pituitary–adrenal (HPA) axis activation occurs in the state of stress; concurrently, the HPA axis is also dysregulated in obesity and metabolic syndrome, making it the most well-understood shared common pathophysiological pathway with MDD. Numerous studies have investigated the effects of different classes of antidepressants on body weight. Previous clinical studies suggest that the tricyclics amitriptyline, nortriptyline and imipramine, and the serotonin norepinephrine reuptake inhibitor mirtazapine are associated with weight gain. Despite the fact that selective serotonin reuptake inhibitor (SSRI) use has been associated with weight loss during acute treatment, a number of studies have shown that SSRIs may be associated with long-term risk of weight gain; however, because of high variability and multiple confounds in clinical studies, the long-term effect of SSRI treatment and SSRI exposure on body weight remains unclear. A recently developed animal paradigm shows that the combination of stress and antidepressants followed by long-term high-fat diet results, long after discontinuation of antidepressant treatment, in markedly increased weight, in excess of what is caused by high-fat diet alone. On the basis of existing epidemiological, clinical and preclinical data, we have generated the testable hypothesis that escalatin

Congenital leptin deficiency and thyroid function

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

Is increased antidepressant exposure a contributory factor to the obesity pandemic?

Major depressive disorder (MDD) and obesity are both common heterogeneous disorders with complex aetiology, with a major impact on public health. Antidepressant prescribing has risen nearly 400% since 1988, according to data from the Centers for Disease Control and Prevention (CDC). In parallel, adult obesity rates have doubled since 1980, from 15 to 30 percent, while childhood obesity rates have more than tripled. Rising obesity rates have significant health consequences, contributing to increased rates of more than thirty serious diseases. Despite the concomitant rise of antidepressant use and of the obesity rates in Western societies, the association between the two, as well as the mechanisms underlying antidepressant-induced weight gain, remain under explored. In this review, we highlight the complex relationship between antidepressant use, MDD and weight gain. Clinical findings have suggested that obesity may increase the risk of developing MDD, and vice versa. Hypothalamic-pituitary-adrenal (HPA) axis activation occurs in the state of stress; concurrently, the HPA axis is also dysregulated in obesity and metabolic syndrome, making it the most well-understood shared common pathophysiological pathway with MDD. Numerous studies have investigated the effects of different classes of antidepressants on body weight. Previous clinical studies suggest that the tricyclics amitriptyline, nortriptyline and imipramine, and the serotonin norepinephrine reuptake inhibitor mirtazapine are associated with weight gain. Despite the fact that selective serotonin reuptake inhibitor (SSRI) use has been associated with weight loss during acute treatment, a number of studies have shown that SSRIs may be associated with long-term risk of weight gain; however, because of high variability and multiple confounds in clinical studies, the long-term effect of SSRI treatment and SSRI exposure on body weight remains unclear. A recently developed animal paradigm shows that the combination of stress and antidepressants followed by long-term high-fat diet results, long after discontinuation of antidepressant treatment, in markedly increased weight, in excess of what is caused by high-fat diet alone. On the basis of existing epidemiological, clinical and preclinical data, we have generated the testable hypothesis that escalating use of antidepressants, resulting in high rates of antidepressant exposure, might be a contributory factor to the obesity epidemi