leptin and Hyperthyroidism

Leptin, a satiety hormone is a protein produced by the adipose tissue that regulates appetite and energetic balance of the body. Results of investigations of serum leptin in patients with hyperthyroidism or hypothyroidism are controversial. Influence of thyroid hormones on leptin secretion is complex and partially unrecognized.

Topics: Adipose Tissue; Humans; Hyperthyroidism; Hypothyroidism; Leptin; Thyroid Hormones

Thyroid hormones (TH) are potent modulators of adaptive thermogenesis and can potentially contribute to development of obesity. The decrease of T(3) in association with reduction of calorie intake is centrally regulated via decreases in leptin and melanocortin concentrations and peripherally via a decrease in deiodinase activity, all aimed at protein and energy sparing. The use of TH in the treatment of obesity is hardly justified except in cases of elevated thyrotropin (TSH) with low/normal T(3) and T(4) and/or a low T(3) or T'(3)/T(4) or a high TSH/T(3) ratio. TH treatment with small doses of T(3) can also be exceptionally applied in obese patients resistant to dietary therapy who are taking beta-adrenergic blockers or with obesity developed after cessation of cigarette smoking and with hyperlipidemia and a concomitant high thryrotropin/T(3) ratio. Supplementation with Se(2+) and Zn(2+) may be tried along with more severe calorie restriction to prevent decline of T(3).

Topics: Animals; Body Weight; Eating; Humans; Hyperthyroidism; Hypothyroidism; Leptin; Models, Biological; Obesity; Thyroid Hormones

Topics: Animals; Body Composition; Carrier Proteins; Humans; Hyperthyroidism; Hypothyroidism; Leptin; Mice; Proteins; Rats; Receptors, Cell Surface; Receptors, Leptin; Thyroid Diseases; Thyroid Gland; Thyroid Hormones

There are potentially complex interrelationships between thyroid function, leptin, ghrelin, body mass index (BMI), and percentage of body fat (%BF). The goal of this study was to determine if normalization of thyroid status in premenopausal women with hyperthyroidism and hypothyroidism would be associated with changes in serum leptin and ghrelin in the absence of thyroid dysfunction treatment-associated changes in BMI and %BF.. The study was carried out in 47 selected premenopausal women: 17 with hyperthyroidism, 11 with hypothyroidism, and 19 healthy individuals who constituted the control group. Patients with thyroid dysfunction were selected for study if their BMI and %BF did not change after treatment of thyroid dysfunction. Subjects in the control group were selected on the basis of the age, BMI, and the %BF characteristics of the patients with thyroid dysfunction. Concentrations of free thyroxine (fT4), free triiodothyronine (fT3), thyrotropin, leptin, and ghrelin in serum were determined before and after treatment of thyroid dysfunction and in the control group.. Serum leptin concentrations were similar in patients with hyperthyroidism and hypothyroidism before treatment and in normal subjects and did not change significantly after treatment of hyperthyroidism or hypothyroidism. Serum ghrelin concentrations were lower in patients with hyperthyroidism, and higher in patients with hypothyroidism than in the control group (hypothyroidism = 2345 (1157-7015) [median (range)], hyperthyroidism = 1205 (438-2914), control = 2398 (1542-4920), p < 0.05).. In premenopausal women with hyperthyroidism or hypothyroidism, treatment of thyroid dysfunction that is not associated with changes in BMI or %BF does not influence serum leptin but does affect serum ghrelin. Thyroid status itself, in the absence of alterations in the BMI and %BF, has an important influence on circulating ghrelin but not leptin.

Topics: Adolescent; Adult; Antithyroid Agents; Blood Pressure; Body Mass Index; Female; Ghrelin; Humans; Hyperthyroidism; Hypothyroidism; Leptin; Methimazole; Middle Aged; Postmenopause; Thyroxine; Triiodothyronine

We investigated the possible correlation between the leptin concentration and the Zn/Cu ratio in the plasma of women with thyroid disorder. Forty women with hypothyroidism (n = 20) or hypothyroidism (n = 20) and 20 euthyroid controls were recruited. The results showed that the women with thyroid disorder (hypothyroidism or hyperthyroidism) had higher plasma leptin concentrations than the normal controls (p < 0.05). Moreover, the plasma leptin concentration had no correlation with plasma thyroid hormone levels in the separate groups, nor among all the participants considered together. A strong correlation (p < 0.005) between leptin and adiposity was only observed in euthyroid women. Plasma values of Zn and Cu and the Zn/Cu ratio were not markedly different among women with altered thyroid status. However, a weak correlation (r = 0.28, p = 0.032) between leptin and the Zn/Cu ratio was found from the pooled data of all participants and retained after adjustment for adiposity. We suggest that there may exist an interaction between the plasma leptin level and thyroid hormone-induced abnormality for selected minerals.

Topics: Adult; Body Composition; Copper; Female; Humans; Hyperthyroidism; Hypothyroidism; Leptin; Thyroid Diseases; Zinc

Thyroid hormones play an essential role in metabolism regulation and circadian rhythm control. Recent studies approved their role in normal development and healthy function of central nervous system (CNS). The thyroid gland is a component of the hypothalamic-pituitary-thyroid axis disrupted during thyrotoxicosis and hypothyroidism, two main clinical conditions that induce more liability against dementia-related disease.. In the first step, this study evaluated the circular level of neuropeptide Y (NPY), leptin, oxytocin, and vasopressin in hyperthyroidism and hypothyroidism patients. In the second step, we investigated neurological and cognitive abnormalities by assessment of the hallmark proteins and peptides such as amyloid β (Aβ) variants, glycogen synthase kinase 3β (GSK-3β), and tau protein in thyroid-deficient samples.. The results show increased content of leptin hormone in patients with hypothyroidism who also manifested high levels of vasopressin. Underactivation and overactivation of the thyroid gland are accompanied by reduced circular oxytocin. We may conclude that thyroid deficiency is associated with neurohormone dysregulation. Interestingly, both patient groups exhibited significant increases in Aβ40 and Aβ42 levels relative to the control group, which was also accompanied by the rise in GSK-3β; this might be interpreted as cholinergic system dysfunction and cognitive impairment. The results revealed tau content increased considerably in thyrotoxicosis but did not change significantly in hypothyroidism compared to the control group.. Therefore, our results have shown that thyroid gland dysfunction is a risk factor for cognitive impairment, mainly through neuroendocrine dysregulation. This study provides a relationship between hyperthyroidism/hypothyroidism and biomarkers of neurological abnormalities in blood serum.

Topics: Amyloid beta-Peptides; Biomarkers; Cognitive Dysfunction; Glycogen Synthase Kinase 3 beta; Humans; Hyperthyroidism; Hypothyroidism; Leptin; Oxytocin; Thyrotoxicosis

Growth hormone (GH) and thyroid hormones are important for children growing. In some obese children a slightly elevated TSH concentration is observed. This may be an adaptive mechanism: stimulation of pro-TRH biosynthesis in the hypothalamus in response to elevated leptin. The increased TSH may also reflect the necessity of maintaining the resting energy expenditure or may be a result of inappropriate, low FT4 concentration. Thus, we evaluated serum TSH and FT4 concentrations in idiopathic short stature (ISS) children (non GH-deficient) and examined the effect of children's nutritional status and levels of selected adipocytokines on thyroid function, searching for the presence of various forms of subclinical hypothyroidism, which may be the cause of the slow growth rate.. The study group included 115 children (50 girls and 65 boys) with ISS, aged (mean ± SD) 10.4 ± 3.34 years. In each child, lipids, TSH, FT4, IGF-1, maxGH during the stimulation tests, leptin, adiponectin and resistin concentrations were determined. Based on BMI SDS, 3 subgroups: slim (n=26), obese (n=21) and normal weight (n=68) were distinguished.. There was no correlation between leptin level and TSH, FT4 levels. The levels of leptin, total cholesterol and LDL-cholesterol in obese short children were significantly higher than in children from other subgroups. In turn, the levels of adiponectin, resistin, TSH and FT4 did not differ between subgroups. In 7% of children, an elevated TSH level was found (but less than 10 mIU/L), with a similar frequency across subgroups. The higher the leptin, the lower maxGH in clonidine stimulation test was recorded.. It seems that in obese children with idiopathic short stature leptin does not increase TSH secretion. This may be related to a disruption of the effect of leptin on TSH production and could indicate wide ranging disturbances of hypothalamic signals, and consequently be the cause of inappropriate GH secretion.

Topics: Adiponectin; Adolescent; Body Height; Child; Cholesterol; Female; Growth Hormone; Human Growth Hormone; Humans; Hyperthyroidism; Leptin; Male; Pediatric Obesity; Resistin; Thyrotropin

Background Melatonin, an important neurohormone released from the pineal gland, is generally accepted to exercise an inhibitor effect on the thyroid gland. Zinc mediates the effects of many hormones and is found in the structure of numerous hormone receptors. Aim The present study aims to examine the effect of melatonin supplementation and pinealectomy on leptin, neuropeptide Y (NPY), melatonin and zinc levels in rats with hypothyroidism and hyperthyroidism. Methods This study was performed on the 70 male rats. Experimental animals in the study were grouped as follows: control (C); hypothyroidism (PTU); hypothyroidism + melatonin (PTU + M); hypothyroidism + pinealectomy (PTU + Pnx); hyperthyroidism (H); hyperthyroidism + melatonin (H + M) and hyperthyroidism + pinealectomy (H + Pnx). Blood samples collected at the end of 4-week procedures were analyzed to determine melatonin, leptin, NPY and zinc levels. Results It was found that thyroid parameters thyroid stimulating hormone (TSH), free triiodthyronine (FT3), free thyroxine (FT4), total T3 (TT3) and total T4 (TT4) decreased in hypothyroidism groups and increased in the groups with hyperthyroidism. The changes in these hormones remained unaffected by melatonin supplementation and pinealectomy. Melatonin levels rose in hyperthyroidism and fell in hypothyroidism. Leptin and NPY levels increased in both hypothyroidism and hyperthyroidism. Zinc levels, on the other hand, decreased in hypothyroidism and pinealectomy, but increased in hyperthyroidism. Conclusion The results of the study demonstrate that hypothyroidism and hyperthyroidism affect leptin, NPY, melatonin and zinc values in different ways in rats. However, melatonin supplementation and pinealectomy do not have any significant influence on the changes occurring in leptin, NPY and zinc levels in thyroid dysfunction.

Topics: Animals; Biomarkers; Dietary Supplements; Disease Models, Animal; Hyperthyroidism; Hypothyroidism; Leptin; Male; Melatonin; Neuropeptide Y; Pineal Gland; Rats; Thyroid Function Tests; Zinc

Since zinc mediates the effects of many hormones or is found in the structure of numerous hormone receptors, zinc deficiency leads to various functional impairments in the hormone balance. And also thyroid hormones have important activity on metabolism and feeding. NPY and leptin are affective on food intake and regulation of appetite. The present study is conducted to determine how zinc supplementation and deficiency affect thyroid hormones (free and total T3 and T4), melatonin, leptin, and NPY levels in thyroid dysfunction in rats. The experiment groups in the study were formed as follows: Control (C); Hypothyroidism (PTU); Hypothyroidism+Zinc (PTU+Zn); Hypothyroidism+Zinc deficient; Hyperthyroidism (H); Hyperthyroidism+Zinc (H+Zn); and Hyperthyroidism+Zinc deficient. Thyroid hormone parameters (FT

Topics: Animals; Biomarkers; Enzyme-Linked Immunosorbent Assay; Hyperthyroidism; Hypothyroidism; Leptin; Male; Melatonin; Neuropeptide Y; Rats; Rats, Sprague-Dawley; Thyroid Hormones; Zinc

Leptin and ghrelin, two peptide hormones with antagonistic effects on satiety and energy balance, could be involved in the pathogenesis of weight loss and polyphagia in cats with hyperthyroidism. Leptin generally decreases appetite and increases energy expenditure, while ghrelin exerts the opposite effects.. Leptin and ghrelin were measured in 42 client owned hyperthyroid cats with a body condition score (BCS) ≤ 5/9 before (T0) and 4 weeks after radioactive iodine treatment (RAIT) (T1). Dependent on the serum total thyroxine concentration concentration at T1, cats were sub-classified as still hyperthyroid (ht-ht) (n = 4), euthyroid (ht-eu) (n = 10) or hypothyroid (ht-hypo) (n = 28). Results were compared to those of 22 healthy, euthyroid control cats with a comparable BCS (≤ 5/9) and age (≥ 8 years) to hyperthyroid cats.. At T0, there were no significant differences between hyperthyroid and control cats for leptin (p = 0.06) or ghrelin concentrations (p = 0.27). At T1, leptin significantly decreased in ht-hypo cats compared to T0 (p = 0.0008) despite a significantly increased body weight in this group (p = 0.0001). Serum ghrelin concentrations did not differ between hyperthyroid cats with a history of polyphagia compared to non-polyphagic cats (p = 0.42). After RAIT, ghrelin concentration significantly increased in all hyperthyroid cats (p < 0.0001), as well as in the subgroups ht-eu (p = 0.014) and ht-hypo (p < 0.0001) compared to their respective T0 baseline concentrations.. Leptin and ghrelin fluctuations may be indicative of changes in metabolic functions in cats with thyroid dysfunction. Leptin fluctuations occurred independently of body weight in different states of thyroid dysfunction; increasing ghrelin concentrations after RAIT suggest a ghrelin-independent mechanism for polyphagia in hyperthyroid cats.

Topics: Animals; Cat Diseases; Cats; Ghrelin; Hyperthyroidism; Hypothyroidism; Iodine Radioisotopes; Leptin

There is insufficient information about the appetite-related hormones orexin-A, nesfatin-1, agouti-related peptide (AgRP), and neuropeptide Y (NPY) in hyperthyroidism. The aim of the present study was to investigate the effects of hyperthyroidism on the basal metabolic rate (BMR) and energy intake, orexin-A, nesfatin-1, AgRP, NPY, and leptin levels in the circulation, and their relationship with each other and on appetite.. In this prospective study, patients were evaluated in hyperthyroid and euthyroid states in comparison with healthy subjects. Twenty-one patients with overt hyperthyroidism and 33 healthy controls were included in the study.. Daily energy intake in the hyperthyroid state was found to be higher than that in the euthyroid state patient group (p=0.039). BMR was higher in hyperthyroid patients than the control group (p=0.018). Orexin-A was lower and nesfatin-1 was higher in hyperthyroid patients compared to the controls (p<0.001), whereas orexin-A increased and nesfatin-1 decreased after euthyroidism (p=0.003, p<0.001). No differences were found in the AgRP, NPY, and leptin levels between the hyperthyroid and euthyroid states and controls (p>0.05). Orexin-A correlated negatively with nesfatin-1 (p=0.042), BMR (p=0.013), free triiodothyronine (fT3; p<0.001), and free thyroxine (fT4; p<0.001) and positively with thyrotropin (TSH; p<0.001). Nesfatin-1 correlated negatively with orexin-A (p=0.042) and TSH (p<0.001) and positively with fT3 (p=0.005) and fT4 (p=0.001). In the regression analysis, "diagnosis of hyperthyroidism" was the main factor affecting orexin-A (p<0.001).. Although it seems that no relationship exists among orexin-A, nesfatin-1, and increased appetite in hyperthyroidism, the orexin-A and nesfatin-1 levels are markedly affected by hyperthyroidism.

Topics: Adult; Agouti-Related Protein; Appetite; Basal Metabolism; Calcium-Binding Proteins; Case-Control Studies; DNA-Binding Proteins; Energy Intake; Female; Graves Disease; Humans; Hyperthyroidism; Leptin; Longitudinal Studies; Male; Middle Aged; Nerve Tissue Proteins; Neuropeptide Y; Nucleobindins; Orexins; Prospective Studies; Thyrotropin; Thyroxine; Triiodothyronine; Young Adult

This study was designed to determine the genotoxicity of a supraphysiological dose of triiodothyronine (T3) in both obese and calorie-restricted obese animals. Fifty male Wistar rats were randomly assigned to one of the two following groups: control (C; n = 10) and obese (OB; n = 40). The C group received standard food, whereas the OB group was fed a hypercaloric diet for 20 weeks. After this period, half of the OB animals (n = 20) were subjected to a 25%-calorie restriction of standard diet for 8 weeks forming thus a new group (OR), whereas the remaining OB animals were kept on the initial hypercaloric diet. During the following two weeks, 10 OR animals continued on the calorie restriction diet, whereas the remaining 10 rats of this group formed a new group (ORS) given a supraphysiological dose of T3 (25 µg/100 g body weight) along with the calorie restriction diet. Similarly, the remaining OB animals were divided into two groups, one that continued on the hypercaloric diet (OB, n = 10), and one that received the supraphysiological dose of T3 (25 µg/100 g body weight) along with the hypercaloric diet (OS, n = 10) for two weeks. The OB group showed weight gain, increased adiposity, insulin resistance, increased leptin levels and genotoxicity; T3 administration in OS animals led to an increase in genotoxicity and oxidative stress when compared with the OB group. The OR group showed weight loss and normalized levels of adiposity, insulin resistance, serum leptin and genotoxicity, thus having features similar to those of the C group. On the other hand, the ORS group, compared to OR animals, showed higher genotoxicity. Our results indicate that regardless of diet, a supraphysiological dose of T3 causes genotoxicity and potentiates oxidative stress.

Topics: Adipose Tissue; Animals; Body Composition; Body Weight; Caloric Restriction; Comet Assay; Energy Intake; Hyperthyroidism; Insulin Resistance; Leptin; Male; Malondialdehyde; Obesity; Rats; Triiodothyronine

Topics: Animals; Antithyroid Agents; Cat Diseases; Cats; Female; Hyperthyroidism; Leptin; Male; Methimazole; Thyroid Hormones; Thyroxine; Treatment Outcome

To analyze the influence of hyperthyroidism on the gene expression and serum concentration of leptin, resistin, and adiponectin in obese animals.. Male Wistar rats were randomly divided into two groups: control (C)-fed with commercial chow ad libitum-and obese (OB)-fed with a hypercaloric diet. After group characterization, the OB rats continued receiving a hypercaloric diet and were randomized into two groups: obese animals (OB) and obese with 25 μg triiodothyronine (T(3))/100 BW (OT). The T(3) dose was administered every day for the last 2 weeks of the study. After 30 weeks the animals were euthanized. Samples of blood and adipose tissue were collected for biochemical and hormonal analyses as well as gene expression of leptin, resistin, and adiponectin.. T(3) treatment was effective, increasing fT(3) levels and decreasing fT(4) and TSH serum concentration. Administration of T(3) promotes weight loss, decreases all fat deposits, and diminishes serum levels of leptin, resistin, and adiponectin by reducing their gene expression.. Our results suggest that T(3) modulate serum and gene expression levels of leptin, resistin, and adiponectin in experimental model of obesity, providing new insights regarding the relationship between T(3) and adipokines in obesity.

Topics: Adiponectin; Adipose Tissue; Animals; Body Weight; Disease Models, Animal; Gene Expression Regulation; Homeostasis; Hyperthyroidism; Leptin; Male; Obesity; Random Allocation; Rats; Rats, Wistar; Resistin; Thyrotropin; Thyroxine; Triiodothyronine

Hyperthyroidism is associated with increased food intake, energy expenditure and altered body composition. This study was aimed to evaluate the role of adipocytokines in weight homeostasis in patients with hyperthyroidism.. Patients (n=27, 11men) with hyperthyroidism (20 Graves' disease, 7 toxic multinodular goiter) with mean age of 31.3±4.2 yr and 28 healthy age and body mass index (BMI) matched controls were studied. They underwent assessment of lean body mass (LBM) and total body fat (TBF) by dual energy X-ray absorptiometer (DXA) and blood sample was taken in the fasting state for measurement of leptin, adiponectin, ghrelin, insulin, glucose and lipids. Patients were re-evaluated after 3 months of treatment as by that time all of them achieved euthyroid state with carbimazole therapy.. The LBM was higher (P<0.001) in healthy controls as compared to hyperthyroid patients even after adjustment for body weight (BW), whereas total body fat was comparable between the two groups. Serum leptin levels were higher in patients with hyperthyroidism than controls (22.3±3.7 and 4.1±0.34 ng/ml, P<0.001), whereas adiponectin levels were comparable. Plasma acylated ghrelin was higher in patients than in controls (209.8±13.3 vs 106.2±8.2 pg/ml, P<0.05). Achievement of euthyroidism was associated with significant weight gain (P<0.001) and significant increase in lean body mass (P<0.001). The total body fat also increased but insignificantly from 18.4±1.8 to 19.9±1.8 kg. There was significant decrease (P<0.05) in serum leptin and acylated ghrelin but adiponectin levels remained unaltered after treatment. Serum leptin positively correlated with TBF and this correlation persisted even after adjustment for BW, BMI, gender and age (r=0.62, P=0.001). However, serum leptin and acylated ghrelin did not correlate with the presence or absence of hyperphagia.. Patients with hyperthyroidism predominantly had decreased lean body mass which increased after achievement of euthyroidism with carbimazole. The hyperphagia and the alterations in weight homeostasis associated with hyperthyroidism were independent of circulating leptin and ghrelin levels.

Topics: Adipose Tissue; Adult; Antithyroid Agents; Body Composition; Body Weight; Carbimazole; Energy Metabolism; Ghrelin; Humans; Hyperphagia; Hyperthyroidism; Leptin; Male; Thyroid Hormones

Thyroid dysfunction can compromise physical capacity. Here, we analyze the effects of hyperthyroidism and hypothyroidism on maximum swim time in rats subjected to acute forced swimming, as an indicator of anaerobic capacity. Animals were forced to swim against a load (5% of body weight) attached to the tail and were killed 48 hours after the last test. Hyperthyroid rats were treated with thyroxine (50 mug/100 g body weight, i. p. for 7 days). The hypothyroid group received 0.03% methimazole in the drinking water for 4 weeks. Thyroid state was confirmed by alterations in serum thyroid-stimulating hormone (TSH), triiodothyronine (T3), thyroxine (T4), and liver mitochondrial glycerol phosphate dehydrogenase (mGPD) activity. Hyperthyroid rats presented significantly lower visceral fat mass (VFM) and higher food intake (p<0.05) with unchanged body weight. Maximum swim time (MST), glycogen content (skeletal muscle and liver), and leptin levels were lower while corticosterone was higher (p<0.05). In hypothyroid rats body weight was lower (p<0.05), without changes in VFM. Tested at 7-day intervals, MST was lower for tests 2, 3, and 4 (p<0.05). Muscle glycogen was higher in extensor digitorum longus (EDL) and soleus (p<0.05), without changes in liver. Serum corticosterone was lower, while leptin was higher (p<0.05). These results suggest that in hyperthyroid and hypothyroid rats, thyroid hormones together with corticosterone and/or leptin may impair exercise capacity differently through its known effects on glycogen metabolism.

Topics: Animals; Body Composition; Corticosterone; Eating; Exercise Tolerance; Glycogen; Hyperthyroidism; Hypothyroidism; Leptin; Liver Glycogen; Male; Muscle, Skeletal; Rats; Rats, Wistar; Swimming; Thyrotropin; Thyroxine

Several authors have shown that secondary hypothyroidism was programed by neonatal thyroxine (T4) treatment. However, the associated changes of body weight (BW) were less studied, especially those related to the body fat proportion. Here, we have evaluated the effect of neonatal thyroxine treatment on BW, fat proportion, serum leptin, and thyroid function of 60-day-old rats. Wistar rats were treated with thyroxine (50 microg/100 g BW, ip) (T) or saline (S), during the first 10 days of life. BW, nose-rump length (NRL), and food consumption were monitored for 60 days, when the animals were sacrificed. Thyroid function was evaluated by thyroid radioiodine uptake (RAIU), serum T3, T4, TSH, and liver mitochondrial alpha-glycerophosphate dehydrogenase (mGPD) and type 1 and 2 deiodinases (D1 and D2) activities, which are thyroid hormone-dependent enzymes. T animals showed lower food intake, BW and NRL, but higher total fat mass (+33%) and serum leptin (+46%). They also showed lower serum T3 (-23%), T4 (-32%), TSH (-36%), RAIU (-29%) and mGPD activity (-22%). Hypothalamic and pituitary D2 activities were higher (+24% and 1.4 fold, respectively), while brown adipose tissue (BAT) D2 and skeletal muscle D1 activities were lower (-30% and -62%, respectively). Thus, neonatal hyperthyroidism programs for a higher fat proportion and hyperleptinemia, which can explain the lower food intake. The TH-dependent enzymes activities changed accordingly, except for the decrease in BAT D2, which may be due the role played by the hyperleptinemia. Finally, the decrease in peripheral deiodination may contribute to a lower me-tabolic rate that may increase the adiposity.

Topics: Adipose Tissue; Animals; Animals, Newborn; Body Weight; Female; Glycerolphosphate Dehydrogenase; Hyperthyroidism; Iodide Peroxidase; Lactation; Leptin; Male; Mitochondria, Liver; Muscles; Pituitary Gland; Rats; Rats, Wistar; Thyroid Function Tests; Thyrotropin; Thyroxine; Triiodothyronine

Leptin has been shown to modulate deiodinase type 1 (D1) and type 2 (D2) enzymes responsible for thyroxine (T4) to triiodothyronine (T3) conversion. Previously, it was demonstrated that a single injection of leptin in euthyroid fed rats rapidly increased liver, pituitary, and thyroid D1 activity, and simultaneously decreased brown adipose tissue (BAT) and hypothalamic D2 activity. We have now examined D1 and D2 activities, two hours after a single subcutaneous injection of leptin (8 microg/100 g BW) into hypo- and hyperthyroid rats. In hypothyroid rats, leptin did not modify pituitary, liver and thyroid D1, and thyroid D2 activity, while pituitary D2 was decreased by 41% (p<0.05) and hypothalamic D2 showed a 1.5-fold increase. In hyperthyroid rats, thyroid and pituitary D1, and pituitary and hypothalamic D2 were not affected by leptin injection, while liver D1 showed a 42% decrease (p<0.05). BAT D2 was decreased by leptin injection both in hypo- and hyperthyroid states (42 and 48% reduction, p<0.001). Serum TH and TSH showed the expected variations of hypo- and hyperthyroid state, and leptin had no effect. Serum insulin was lower in hypothyroid than in hyperthyroid rats and remained unchanged after leptin. Therefore, acute effects of leptin on D1 and D2 activity, expect for BAT D2, were abolished or modified by altered thyroid state, in a tissue-specific manner, showing an IN VIVO interplay of thyroid hormones and leptin in deiodinase regulation.

Topics: Adipose Tissue; Adipose Tissue, Brown; Animals; Hyperthyroidism; Hypothalamus; Hypothyroidism; Iodide Peroxidase; Leptin; Liver; Male; Nutritional Status; Organ Specificity; Pituitary Gland; Rats; Rats, Wistar; Thyroid Gland

The aims of this work were to determine the effect of hypothyroidism on insulin-stimulated glucose turnover and to unravel the potential mechanisms involved in such an effect.. Hypothyroidism was induced by administration of propylthiouracil, with partial T4 substitution. Euglycaemic-hyperinsulinaemic clamps, associated with the labelled 2-deoxy-D-glucose technique for measuring tissue-specific glucose utilisation, were used. To assess a possible involvement of leptin in the modulation of glucose metabolism by hypothyroidism, leptin was infused intracerebroventricularly for 6 days. A group of leptin-infused rats was treated with rT3 to determine a potential role of T3 in mediating the leptin effects.. Compared with euthyroid rats, hypothyroid animals exhibited decreased overall glucose turnover and decreased glucose utilisation indices in skeletal muscle and adipose tissue. Leptinaemia in hypothyroid rats was lower while resistin mRNA expression in adipose tissue was higher than in euthyroid animals. Intracerebroventricular leptin infusion in hypothyroid rats partially restored overall, muscle and adipose tissue insulin-stimulated glucose utilisation and improved the reduced glycaemic response observed during insulin tolerance tests. The leptin effects were due neither to the observed increase in plasma T3 levels nor to changes in the high adipose tissue resistin expression of hypothyroid rats. The administration of leptin to hypothyroid animals was accompanied by increased expression of muscle and adipose tissue carnitine palmitoyl transferases, decreased plasma NEFA levels and reduced muscle triglyceride content.. Hypothyroidism is characterised by decreased insulin responsiveness, partly mediated by an exaggerated glucose-fatty acid cycle that is partly alleviated by intracerebroventricular leptin administration.

Topics: Adipose Tissue; Animals; Blood Glucose; Carnitine O-Palmitoyltransferase; Energy Metabolism; Fatty Acids, Nonesterified; Gene Expression; Glucose; Glucose Clamp Technique; Hormones, Ectopic; Hyperthyroidism; Insulin; Insulin Resistance; Iodide Peroxidase; Iodothyronine Deiodinase Type II; Leptin; Male; Muscle, Skeletal; Propylthiouracil; Rats; Rats, Wistar; Resistin; Thyrotropin; Thyroxine; Triglycerides; Triiodothyronine; Triiodothyronine, Reverse

Leptin is considered to play a role in maintenance of energy balance and body weight by neuroendocrine mechanisms. The physiological mechanisms for thyroid hormone-induced alteration in serum leptin are not well known. In the present study, the relationship between thyroid hormones and leptin levels was investigated in patients with overt hypothyroidism and hyperthyroidism before and after successful treatment. Leptin levels were determined by radioimmunoassay and body mass index (BMI) was calculated for each subject. Serum leptin levels of 26 hypothyroid and 22 hyperthyroid patients were compared with those of 20 healthy volunteers who comprised the controls. Serum leptin levels of hypothyroid patients (28.4 +/- 4.1 ng/ml) were found to be significantly higher than the controls (19.1 +/- 3.2 ng/ml) (p<0.01), whereas hyperthyroid patients had lower levels (10.7 +/- 1.2 ng/ml) (p<0.01). In hypothyroid patients, serum leptin levels were decreased significantly to 20.6 +/- 2.1 ng/ml with thyroxin treatment (p<0.05). However, in hyperthyroid group, serum leptin levels were increased to 12.4 +/- 2.2 ng/ml by treatment (p>0.05). BMI was not changed with the treatment in either group. The serum leptin levels were correlated with BMI and thyrotropin (TSH) in both hypothyroid and hyperthyroid patients. Serum leptin levels are affected in thyroid disorders and the correlation of leptin with TSH is independent of thyroid hormones.

Topics: Adult; Body Mass Index; Female; Humans; Hyperthyroidism; Hypothyroidism; Leptin; Male; Middle Aged; Thyroid Hormones; Thyrotropin; Thyroxine; Triiodothyronine

Thyroid dysfunction is associated with metabolic changes that affect mass and adipocyte function, as well as lipid and carbohydrate metabolism. Adipose tissue performs complex metabolic and endocrine functions. Leptin and adiponectin are two of the most important adipocytokines, both involved in the regulation of intermediate metabolism. The aim of this study was to evaluate the relationships between thyroid status and circulating levels of the two adipose tissue hormones. We studied 15 patients with hyperthyroidism, 15 patients with hypothyroidism and 15 euthyroid subjects, all matched by sex, age and body mass index (BMI). Serum concentrations of free thyroxine, free tri-iodothyronine, thyrotropin, leptin and adiponectin and anthropometric parameters (weight, height, BMI) were assessed. No significant difference was found among the 3 groups, as assessed by Student's t-test, both for adiponectin and leptin. We conclude that metabolic changes associated with thyroid dysfunction are not related to variations in serum levels of adiponectin or leptin.

Topics: Adiponectin; Adipose Tissue; Adult; Anthropometry; Case-Control Studies; Female; Humans; Hyperthyroidism; Hypothyroidism; Intercellular Signaling Peptides and Proteins; Leptin; Male; Middle Aged; Proteins; Thyroid Gland; Thyrotropin; Thyroxine; Triiodothyronine

Increased food intake is characteristic of hyperthyroidism, although this is presumed to compensate for a state of negative energy balance. However, here we show that the thyroid hormone T(3) directly stimulates feeding at the level of the hypothalamus. Peripheral administration of T(3) doubled food intake in ad libitum-fed rats over 2 h and induced expression of the immediate early gene, early growth response-1, in the hypothalamic ventromedial nucleus (VMN), whereas maintaining plasma-free T(3) levels within the normal range. T(3)-induced feeding occurred without altering energy expenditure or locomotion. Injection of T(3) directly into the VMN produced a 4-fold increase in food intake in the first hour. The majority of T(3) in the brain is reported to be produced by tissue-specific conversion of T(4) to T(3) by the enzyme type 2 iodothyronine deiodinase (D2). Hypothalamic D2 mRNA expression showed a diurnal variation, with a peak in the nocturnal feeding phase. Hypothalamic D2 mRNA levels also increased after a 12- and 24-h fast, suggesting that local production of T(3) may play a role in this T(3) feeding circuit. Thus, we propose a novel hypothalamic feeding circuit in which T(3), from the peripheral circulation or produced by local conversion, stimulates food intake via the VMN.

Topics: Adipose Tissue; Animals; Body Weight; Circadian Rhythm; Eating; Energy Metabolism; Fasting; Gene Expression Regulation, Enzymologic; Hyperthyroidism; Iodide Peroxidase; Iodothyronine Deiodinase Type II; Leptin; Male; Rats; Rats, Wistar; RNA, Messenger; Thyroxine; Triiodothyronine; Ventromedial Hypothalamic Nucleus

Thyroid hormones as well as the recently discovered secretory products of adipose tissue adiponectin and resistin take part in energy metabolism. To study the changes in the adipocyte hormones with changes in the thyroid functional status, we measured adiponectin, resistin, and leptin in 69 subjects with Graves' disease before and 32 patients at follow up after treatment for hyperthyroidism at hypothyroid state. Concentrations of serum adiponectin and resistin were higher in hyperthyroid state than in hypothyroid state (adiponectin: 5.73 +/- 1.1 vs. 3.0 +/- 0.5 ng/ml, P = 0.03) (resistin: 6.378 +/- 0.6 vs. 5.81 +/- 0.57 ng/ml, P < 0.0001). Resistin levels correlate positively with free t4(r = 0.37, P < 0.01), free t3 levels(r = 0.33, P < 0.01) and negatively with TSH(r = -0.22, P < 0.05). Adiponectin levels correlate with free t4(r = 0.33, P < 0.01) and free t3 (r = 0.44, P < 0.01). Though the adiponectin levels did not correlate with leptin or resistin levels, strong positive correlation of both resistin and adiponectin with thyroid hormones is noted. Serum levels of leptin did not change with change in the thyroid functional status (leptin: 53.38 +/- 2.47 vs. 55.10 +/- 2.58 NS). Leptin levels did not correlate with resistin and adiponectin. We conclude that thyroid function has effect on adipocyte hormones adiponectin and resistin but not leptin.

Topics: Adipocytes; Adiponectin; Graves Disease; Hormones, Ectopic; Humans; Hyperthyroidism; Intercellular Signaling Peptides and Proteins; Leptin; Resistin; Thyroid Gland

We investigated the influence of hypo- and hyperthyroidism on the ability of leptin to modulate TSH secretion. Two hours after receiving leptin (8 mug leptin/100 g BW; s.c.), hyperthyroid rats (10 mug thyroxine (T4)/100 g body weight (BW) for 5 days) showed a 1.7-fold increase in serum TSH (P<0.05); in hypothyroid rats, leptin had no effect. Hemi-pituitaries of hyperthyroid rats incubated with 10(-9) and 10(-7)M leptin showed reductions in TSH release of 40 and 50% respectively (P<0.05); incubation with 1:2000 and 1:500 dilutions of antiserum against leptin resulted in 3- and 4-fold higher TSH release (P<0.05 and P<0.001 respectively). However, in hypothyroid pituitaries leptin or the antiserum had no effect. The results suggest that the in vivo and in vitro responsiveness of TSH to leptin is abolished in hypothyroidism and is preserved in short-term hyperthyroidism, in comparison to previous reports in euthyroidism. In addition, the inhibitory action of pituitary leptin is enhanced in hyperthyroid glands, which may suggest a role for locally produced leptin in the suppression of TSH release associated with hyperthyroidism.

Topics: Animals; Hyperthyroidism; Hypothyroidism; Immune Sera; Leptin; Male; Organ Culture Techniques; Pituitary Gland, Anterior; Rats; Rats, Wistar; Thyroid Hormones; Thyrotropin

Topics: Chorionic Gonadotropin; Female; Humans; Hyperemesis Gravidarum; Hyperthyroidism; Leptin; Pregnancy; Thyroid Hormones

The hormone leptin is considered to have a role in the prevention of osteoporosis and probably acts on bone tissue through inhibition of osteoclasia. Its action has been attributed to interference in osteoprotegerin (OPG)/OPG-ligand equilibrium. Contradictory data also have been reported, casting doubts on the positive effect on bone mass of the hormone, at least in males. To date, the relation between serum leptin levels of dialysis patients and renal osteodystrophy, defined by histomorphometric and histodynamic parameters of bone, has not been studied.. The study included 46 hemodialysis patients (32 men, 14 women; age, 57.2 +/- 11.4 years). A transiliac bone biopsy after double-tetracycline labeling was performed for histological, histomorphometric, and histodynamic studies. Blood samples were drawn for leptin, intact parathyroid hormone (PTH), whole PTH (PTH1-84), OPG, bone alkaline phosphatase, calcium, phosphate, 25-hydroxycholecalciferol, and calcitriol. Serum leptin was measured by means of a radioimmunoassay.. Eighteen patients had mixed osteodystrophy (MO); 17 patients, hyperparathyroidism; 9 patients, adynamic bone disease (ABD); and 2 patients, osteomalacia. Aluminum histochemistry results were positive in 1 patient with ABD and 1 patient with MO. A sex difference was found in serum leptin levels (48.9 +/- 38 ng/mL in women and 12.2 +/- 13.2 ng/mL in men; P < 0.0002). In the entire population, lnleptin correlated significantly with body mass index (BMI; P < 0.01). SD score (SDS) leptin (adjusted for BMI, sex, and age) correlated inversely with PTH1-84 level and osteoclastic surface (OcS/BS; P < 0.05) and had a borderline correlation with bone formation rate. Correlations between leptin levels and other parameters were enhanced in men. SDS leptin correlated inversely with OcS/BS (P < 0.01), osteoclastic number (P < 0.01), and mineral apposition rate (P < 0.01). In addition, SDS leptin had a borderline inverse correlation with osteoblast surface (P < 0.06) and significant correlation with OPG level (P < 0.05). No difference was found in serum leptin levels between histological groups.. The reported data confirm the finding of a positive relation between serum leptin level and BMI and greater levels in women compared with men. Serum leptin level is connected to bone resorption and also bone formation, both inversely related to serum leptin levels. The decrease in osteoclasia that accompanies increasing serum leptin levels does not seem to be related to an enhanced OPG effect because it was accompanied by decreased OPG levels. Low-turnover bone disease does not appear to be caused by increased serum leptin levels. The nature of the interrelation between serum leptin and PTH1-84 levels requires further study.

Topics: Aged; Biomarkers; Body Mass Index; Chronic Kidney Disease-Mineral and Bone Disorder; Female; Glycoproteins; Humans; Hyperthyroidism; Kidney Failure, Chronic; Leptin; Male; Middle Aged; Osteomalacia; Osteoprotegerin; Parathyroid Hormone; Receptors, Cytoplasmic and Nuclear; Receptors, Leptin; Receptors, Tumor Necrosis Factor; Renal Dialysis; Sex Factors; Statistics as Topic

Adipose tissue is a hormonally active system that produces and releases different bioactive substances. Leptin, adiponectin and resistin are some of the recently discovered adipocytokines that participate in the regulation of intermediate metabolism. The aim of this study was to evaluate the circulating levels of leptin, adiponectin and resistin in patients with thyroid dysfunction before and after normalization of thyroid function with appropriate therapy.. We studied 20 patients with hyperthyroidism (16 women and 4 men; mean age 47.2 +/- 3.9 years) and 20 patients with hypothyroidism (17 women and 3 men; 51.5 +/- 4.1 years). A group of 20 euthyroid subjects served as control group. Patients were evaluated at the time of diagnosis and again after normalization of thyroid function with appropriate therapy. Serum concentrations of free T4 (FT4), total T3, TSH, insulin, leptin, adiponectin and resistin were measured in all subjects.. Hyperthyroid patients showed significantly decreased leptin levels in comparison with controls (11.0 +/- 1.1 vs. 30.4 +/- 5.0 microg/l, P < 0.001). No significant differences in adiponectin levels between hyperthyroid and control groups were found (27.8 +/- 4.0 vs. 46.0 +/- 12.0 mg/l, NS). Patients with hyperthyroidism exhibited reduced resistin levels in comparison with euthyroid subjects (6.4 +/- 0.8 vs. 8.4 +/- 0.7 microg/l, P < 0.05). Normalization of circulating thyroid hormone was accompanied by a nonsignificant increase in leptin levels (12.9 +/- 1.7 microg/l, P < 0.01 vs. control) and no significant modification both in adiponectin (32.0 +/- 7.1 mg/l, NS) and resistin (5.4 +/- 0.7 microg/l, NS) levels. Adjustment of adipocytokine concentrations for body mass index (BMI) showed that treatment of hyperthyroidism induced a significant reduction in adjusted resistin concentrations (0.21 +/- 0.03 vs. 0.28 +/- 0.03 microg/l/BMI units, P < 0.05), with no changes in adjusted leptin and adiponectin. Hypothyroid patients showed significantly lower leptin levels compared with the controls (16.0 +/- 3.5 vs. 30.4 +/- 5.0 microg/l, P < 0.05). Adiponectin levels in patients with hypothyroidism (71.8 +/- 16.0 mg/l) were similar to those in the control group and were not modified with therapy. Resistin levels were significantly reduced among hypothyroid patients (5.8 +/- 1.0 microg/l, P < 0.05), and were not increased after levothyroxine therapy. A significant rise in BMI-corrected leptin levels was observed after replacement therapy, with no changes in adiponectin- and resistin-corrected values.. The results suggest that (1) low serum leptin levels are present in both hyperthyroid and hypothyroid patients but are only increased after therapy in the latter; (2) resistin might be implicated in the insulin resistance state that accompanies thyrotoxicosis; and (3) inadequate secretion of adiponectin seems to have no role in metabolic changes associated with thyroid dysfunction.

Topics: Adiponectin; Adipose Tissue; Adult; Case-Control Studies; Cytokines; Female; Hormones, Ectopic; Humans; Hyperthyroidism; Hypothyroidism; Intercellular Signaling Peptides and Proteins; Leptin; Male; Middle Aged; Proteins; Regression Analysis; Resistin; Treatment Outcome

We examined the effects of thyroid status on cocaine- and amphetamine-regulated transcript and agouti-related peptide expression in the rat hypothalamus. Hypo- and hyperthyroidism were induced in adult male rats, and the mRNA content of cocaine- and amphetamine-regulated transcript and agouti-related peptide was determined using in situ hybridization. Hyperthyroidism induces a reduction in cocaine- and amphetamine-regulated transcript mRNA levels in the paraventricular nucleus, without any change in the arcuate and dorsomedial nuclei and in the lateral hypothalamic area. On the other hand, hypothyroidism had not effect on cocaine- and amphetamine-regulated transcript expression in any of these nuclei. Agouti-related peptide expression in the arcuate nucleus was not affected by the thyroid status. These data indicate that the increments in food intake in hyperthyroidism could be mediated, at least in some extent, by a decreased expression, at the paraventricular nucleus of the hypothalamus, of the anorexigenic cocaine- and amphetamine-regulated transcript peptides.

Topics: Agouti-Related Protein; Amitrole; Animals; Appetite Regulation; Body Weight; Down-Regulation; Enzyme Inhibitors; Hyperthyroidism; Hypothyroidism; Intercellular Signaling Peptides and Proteins; Leptin; Male; Nerve Tissue Proteins; Neurons; Paraventricular Hypothalamic Nucleus; Proteins; Rats; Rats, Sprague-Dawley; RNA, Messenger; Thyrotropin; Thyroxine; Up-Regulation

Leptin, a recently discovered protein produced in adipocytes, regulates body weight by suppressing food intake and/or increasing energy expenditure. Thyroid hormones, which increase the basal metabolic rate and thermogenesis, have been reported to be one of leptin's regulating factors because alternations in thyroid status might lead to compensatory changes in circulating leptin.. The aim of this study was to assess the influence of sequential changes in thyroid function on serum leptin levels.. The thyroid function status of 65 patients (55 women and 10 men, aged 40.6 +/- 15.2 years, mean +/- SD) with differentiated thyroid cancer who had received near-total thyroidectomy was studied before I-131 ablation therapy and after 2-4 and 6 months of levo-thyroxine suppressive therapy. Thirty-three (26 women, seven men; aged 41.0 +/- 10.4 years, mean +/- SD) of them were found to have become hypothyroid, then euthyroid and subsequently subclinically hyperthyroid. Their body mass index (BMI), body fat (%BF) by electrical bioimpedance, thyroid function and fasting serum leptin in these states were assessed and compared to those of 38 controls (30 women, eight men, aged 40.2 +/- 11.3 years, mean +/- SD). The controls had no past history or family history of thyroid diseases, and had the same range of BMI, between 20 and 30 kg/m2, as the patients.. No difference in serum leptin levels was found between patients and controls with comparable age, sex, and BMI distribution in the euthyroid state. Using a repeated measures anova, tests of TSH, free T4 (FT4), BMI,%BF and leptin were performed on the 33 patients with sex as a grouping factor and thyroid state as a time factor. The sex difference for %BF and leptin proved to be statistically significant (P < 0.0001, and P = 0.0003, respectively). Serum leptin levels increased significantly from the hypothyroid to the subclinical hyperthyroid state (P < 0.0001) with a more pronounced increase found in females than in males (P = 0.03). Change of BMI during sequential thyroid function alterations was significant (P = 0.04) while change in %BF was not significant (P = 0.09). Pearson correlation analysis showed that serum leptin levels significantly correlated with BMI, %BF, FT4, and TSH (all P < 0.05). Using the generalized estimating equations, multivariate regression analysis revealed that FT4 was a statistically independent predictor for serum leptin (P < 0.0001). While other parameters were held constant, the mean serum leptin level increased by 1.47 units when serum FT4 was increased by one unit.. In conclusion, our data indicate that circulating thyroid hormone plays a relevant role in regulating leptin metabolism independent of BMI and body fat.

Topics: Adult; Analysis of Variance; Body Composition; Body Mass Index; Case-Control Studies; Female; Humans; Hyperthyroidism; Hypothyroidism; Iodine Radioisotopes; Leptin; Male; Middle Aged; Sex Factors; Thyroid Hormones; Thyroid Neoplasms; Thyroidectomy; Thyrotropin; Thyroxine

Leptin regulates energy production rates and body weight, which are frequently altered in hyperthyroidism. Data on a possible interaction between leptin and thyroid hormones are controversial. We assessed leptin serum concentrations, BMI, proportional fat tissue mass and thyroid hormones in hyperthyroid patients in a long-term follow-up after radioiodine therapy.. The study included 28 hyperthyroid patients (mean age 66 y) before and up to one y after radioiodine therapy. Leptin and thyroid hormones, general parameters, BMI, proportional fat tissue (PFT) measurements by DEXA and thyroid morphology were recorded. Twenty-four age-matched euthyroid individuals (mean age 63 y) served as controls.. At baseline, leptin concentrations were significantly decreased in all hyperthyroid patients as compared to controls. One year after radioiodine therapy, 71% of the patients were euthyroid (group A) and 29% remained hyperthyroid (group B). BMI and PFT increased in both groups. While leptin concentrations remained low in group B, they normalised in group A after 6 to 12 months. Changes in leptin and thyroid hormone concentrations were positively correlated in group A patients (r=0.49, P=0.03) but not in patients remaining hyperthyroid.. Our data indicate a dissociation in the regulation of plasma leptin and BMI as well as proportional fat tissue in hyperthyroid patients which may be attributable to differences in lean and adipose mass weight gain after radioiodine therapy or direct influences of thyroid hormones on leptin regulation. International Journal of Obesity (2001) 25, 115-120

Topics: Absorptiometry, Photon; Adipose Tissue; Aged; Aged, 80 and over; Body Mass Index; Body Weight; Bone Density; Female; Humans; Hyperthyroidism; Iodine Radioisotopes; Leptin; Male; Middle Aged; Thyroid Hormones; Thyrotropin

To study the influence of thyroid hormones on the relationship between serum leptin and fat mass, as well as on energy and macronutrient balance.. Rats with different thyroid states were obtained by 7 and 15 days of treatment with the antithyroid drug propylthiouracil or with triiodothyronine (T3).. Energy balance, macronutrient balance and serum leptin concentrations.. In hypothyroid rats we found a decrease in metabolizable energy (ME) intake and energy expenditure together with an increase in lipid gain/lipid intake ratio and a decrease in protein gain/protein intake ratio. Consequently, body lipid percentage significantly increased compared to euthyroid rats. Hyperthyroid rats first increased energy expenditure and later ME intake, so that increased metabolism was balanced by increased intake, and energy gain was similar to that found in euthyroid rats.. These results indicate that T3 plays a major role in the maintenance of energy and lipid balance. Our results also indicate that an inverse relationship exists between T3 and leptin serum concentrations, and that this relationship is not only the result of changes in body fat stores induced by changed T3 concentrations.

Topics: Adipose Tissue; Animals; Body Composition; Energy Metabolism; Fatty Acids, Nonesterified; Hyperthyroidism; Hypothyroidism; Leptin; Male; Obesity; Rats; Rats, Wistar; Triiodothyronine

To determine the dependence of plasma leptin concentrations upon circulating noradrenaline (NA) and thyroid hormones (TH) in humans.. Cross-sectional study in 40 newly diagnosed untreated patients with primary thyroid disease, and 69 lean and obese euthyroid control subjects.. Plasma leptin, NA, free T3 (fT3) and TSH in the fasting state. Anthropometry and % body fat (electrical bioimpedance).. Leptin levels were highest in 37 obese euthyroid and 22 hypothyroid (median [interquartiles]31.5 [19.0- 48.0], 19.2 [11.5-31.5] ng ml(-1)), and lowest in 32 lean euthyroid and 18 hyperthyroid subjects (6.6 [3.9-14.4], 8.9 [5.5-11.1]; ANOVA, P< 0.0001). Plasma NA was similar in all groups (P= n.s.). In obese controls, TSH correlated with % body fat and leptin (r= 0.67, r= 0.61; P< 0.001). Treatment of hypothyroidism (n= 10) with T4 reduced leptin from 20.8 [11.8-31.6] to 12.9[4.6-21.2] (P= 0.005) with no change in BMI.. Thyroid status modifies leptin secretion independently of adiposity and NA. The data suggest leptin-thyroid interactions at hypothalamic and adipocyte level.

Topics: Female; Humans; Hyperthyroidism; Hypothyroidism; Leptin; Male; Norepinephrine; Obesity; Sympathetic Nervous System; Thyroid Gland; Thyrotropin; Thyroxine; Triiodothyronine

The present study was undertaken to determine whether thyroid hormones affect serum leptin levels in patients with hyperthyroidism. In 32 female patients with hyperthyroidism and 30 body mass index (BMI)-matched control subjects, there was no difference in serum leptin concentrations (9.0+/-1.0 v 8.2+/-0.9 microg/L). The serum leptin levels were compared with the expected values for serum leptin derived from the corresponding BMI with the formula for the control subjects (serum leptin [micrograms per liter] = 0.976 x BMI [kilograms per square meter] - 11.933, P < .001) and are expressed as the percent deviation (%leptin). There was a weak but significant positive correlation between serum free thyroxine (T4) levels and %leptin in the combined analysis of patients with hyperthyroidism and control subjects (r = .28, P < .05). Multiple regression analysis also revealed the independent contribution of free T4 levels to serum leptin. Antithyroid therapy ameliorated the hyperthyroidism and increased the BMI by 7.8% and the percent body fat by 9.9% in a subgroup of 21 patients with hyperthyroidism. However, serum leptin levels did not change during the 2-month therapeutic period (from 9.8+/-1.4 to 8.7+/-1.0 microg/L), and accordingly, %leptin significantly decreased from 133%+/-16% to 98%+/-11% (P < .05). A total of 6 months of observation in 12 hyperthyroid patients showed the same alterations in the anthropometric indexes, serum leptin, and %leptin. These results indicate that serum leptin is slightly increased in subjects with moderate hyperthyroidism, possibly due to the direct action of thyroid hormone, and the levels decline in accordance with the attainment of euthyroidism.

Topics: Adipose Tissue; Adolescent; Adult; Aged; Body Mass Index; Female; Humans; Hyperthyroidism; Leptin; Middle Aged; Thyrotropin

This work was undertaken to examine the relationship between thyroid hormone and serum leptin concentration. This study included 368 Japanese female subjects (27 were affected with pretreatment hyperthyroidism, 68 with hyperthyroidism during treatment, 19 with pretreatment hypothyroidism, 57 with hypothyroidism during treatment and 197 euthyroid control subjects) and 60 control male subjects. In the control group, serum leptin levels in males were lower than those recorded in females (mean +/- SD; 4.6 +/- 4.1 vs 9.5 +/- 6.4 ng/ml, p < 0.001). The leptin values correlated well with body mass index (BMI) and body fat mass (BFM) in both control male and female subjects (p < 0.001 for each). The serum leptin levels in pretreatment female patients with hyperthyroidism were significantly lower than those in the pretreatment patients with primary hypothyroidism and control female subjects (6.4 +/- 3.0 vs 9.7 +/- 6.3, 9.5 +/- 6.4 ng/ml; p < 0.05, 0.02, respectively), but after adjusting for BMI and BFM, the difference was mainly due to the significantly different BMI and BFM. Furthermore, serum leptin did not change significantly during the treatment in hyper and hypothyroidism. There was no correlation between serum leptin and thyroid hormones or lipids levels in female patients with thyroid disorders. Adiposity and gender were the major determinants of leptin concentration, but thyroid hormones did not appear to play any relevant role in leptin synthesis and secretion in human.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Body Weight; Case-Control Studies; Female; Humans; Hyperthyroidism; Hypothyroidism; Leptin; Lipids; Middle Aged; Reference Values; Thyroid Diseases; Thyroid Hormones

Plasma leptin is considered to play a role in maintenance of energy balance and body weight by neuroendocrine mechanisms. Thyroid hormones are permissive for adrenergic activation, which in turn has been shown to decrease leptin expression. This study was therefore designed to test the hypothesis that hyperthyroidism results in lower leptin concentrations, whereas hypothyroidism leads to higher plasma leptin concentrations. In addition, the effects of normalization of thyroid function on plasma leptin were investigated.. Fasting plasma leptin concentrations and body fat mass (total body electrical conductivity) were measured in patients with overt hypothyroidism and hyperthyroidism before and after successful treatment. Plasma leptin, glucose, insulin and free fatty acid concentrations were monitored during an oral glucose tolerance test (OGTT 75 g).. Fasting plasma leptin concentrations were similar in lean patients, independently of their thyroid function (hyperthyroid 12.5 +/- 2 ng mL-1, hypothyroid 10.2 +/- ng mL-1, euthyroid 12.7 +/- 3 ng mL-1). In obese hypothyroid patients, plasma leptin was threefold higher (P < 0.0005) than in lean hypothyroid patients, twofold higher (P < 0.005) than in obese hyperthyroid patients matched for fat mass and 30% increased (P < 0.01) compared with obese euthyroid subjects. There were no differences between fasting and post-prandial (OGTT) leptin concentrations in any group. Normalization of thyroid function did not affect plasma leptin, which remained elevated (P < 0.005) in formerly obese hypothyroid patients. Plasma leptin was not associated with serum thyroid hormones but highly correlated with body mass index and body fat mass in all patients (r = 0.85, P < 0.001). Plasma leptin correlated with plasma insulin concentration only in hyperthyroid patients (P < 0.01, r = 0.64), who presented with blunted stimulation of insulin release and higher plasma glucose (P < 0.05) than hypothyroid subjects.. The results indicate that (a) the correlation of leptin with body fat mass is preserved in thyroid dysfunction, (b) plasma leptin is markedly increased in obese hypothyroid hyperinsulinaemic patients and (c) plasma leptin is not affected by oral glucose loading.

Topics: Adult; Blood Glucose; C-Peptide; Fatty Acids, Nonesterified; Female; Glucose Tolerance Test; Humans; Hydrocortisone; Hyperinsulinism; Hyperthyroidism; Hypothyroidism; Insulin; Leptin; Male; Middle Aged; Obesity; Proteins

The physiological consequences and mechanism(s) for thyroid hormone-induced alterations in serum leptin are not known. To address this, leptin expression in rats was evaluated in relationship to food intake, fat mass, and body temperature in rats with pharmacologically altered thyroid status. Total body weight, food intake, and temperature were decreased in hypothyroid rats. Fat weight was decreased in both chronically hypothyroid and hyperthyroid rats (n = 6/group). Serum leptin was linearly correlated with fat weight, epididymal and retroperitoneal fat leptin mRNA concentration, but not total body weight. Serum leptin was decreased in the chronically hyperthyroid rats. When fat weight was used as a covariant, serum leptin was not different between the three groups. Epididymal fat leptin mRNA was higher in euthyroid (n = 7) than in hypothyroid and hyperthyroid rats. Retroperitoneal fat leptin mRNA was not affected by thyroid status. A positive linear relationship between food intake and free triiodothyronine (FT3) index was observed, but not between food intake and serum leptin alone. In a time course study, serum leptin, epididymal fat leptin mRNA content, and fat weight did not change within 24 hours of high-dose triiodothyronine (T3) (n = 6/group), but both temperature and epididymal fat S14 mRNA content rapidly increased. These findings demonstrate that thyroid state influences circulating leptin levels, but primarily does so indirectly through the regulation of fat mass. Leptin does not influence core body temperature across thyroidal state. Finally, thyroid state is more important to regulate food intake, through an as yet undefined mechanism, than are thyroid state-associated changes in serum leptin.

Topics: Adipose Tissue; Animals; Body Temperature; Body Weight; Energy Intake; Humans; Hyperthyroidism; Hypothyroidism; Leptin; Male; Organ Size; Proteins; Rats; Rats, Sprague-Dawley; Regression Analysis; RNA, Messenger; Thyroid Gland; Transcription, Genetic; Triiodothyronine

In this study, plasma leptin concentrations were measured in rats artificially rendered hyper- or hypothyroid by administration of thyroxine or TRH, by administration of methimazole, or by thyroidectomy. Compared with those in untreated controls, leptin immunoreactivity was not affected in the hyperthyroid state, but was significantly increased in hypothyroid animals. Methimazole administration for longer time periods caused a stepwise increase in plasma leptin immunoreactivity. Greatest leptin concentrations were seen after 28 days of methimazole. Seven days after withdrawal of the methimazole, leptin concentrations no longer differed from those observed in control animals. In hypothyroid animals, expression of leptin mRNA was increased in both retroperitoneal and epididymal adipose tissue, whereas no difference was seen for subcutaneous or mesenteric fat. Incubation of rat leptin with plasma of eu- or hypothyroid rats and subsequent HPLC analysis of leptin plasma peaks gave no indication of an altered hormone stability. We conclude that, in hypothyroid rats, leptin concentrations may be increased as a result of stimulated leptin synthesis in retroperitoneal and epididymal adipose tissue.

Topics: Adipose Tissue; Analysis of Variance; Animals; Antithyroid Agents; Chromatography, Gel; Chromatography, High Pressure Liquid; Hyperthyroidism; Hypothyroidism; Leptin; Male; Methimazole; Radioimmunoassay; Rats; Rats, Wistar; RNA, Messenger; Thyroidectomy; Thyrotropin-Releasing Hormone; Thyroxine

Leptin, the obese gene product, is secreted exclusively by adipocytes and is thought to act as a lipostatic signal that regulates body weight homeostasis. We previously reported that thyroid hormone is one of the up-regulating factors of leptin in vitro. T3, at physiological concentrations, stimulates leptin mRNA expression and leptin secretion by 3T3-L1 adipocytes. The aim of this study was to explore the role of thyroid hormone in the regulation of leptin in humans.. A total of 59 non-obese women aged 38.4 +/- 1.8 years (mean +/- SEM) were studied: 19 patients with hyperthyroidism, 17 patients with hypothyroidism, and 23 normal control subjects. The correlation between serum leptin concentrations and body mass index (BMI) was analyzed, and serum leptin levels were compared among the three groups.. Serum leptin concentrations were measured by radioimmunoassay.. Serum leptin concentrations after logarithmic transformation were correlated significantly (P < 0.05) with BMI in the hyperthyroid (r = 0.46), the hypothyroid (r = 0.84), and normal (r = 0.63) groups. Even though age, body weight, and BMI were similar in all groups, serum leptin levels in the hypothyroid patients (5.30 +/- 1.12 micrograms/l) were significantly (P < 0.05) lower than in the hyperthyroid and normal groups (6.87 +/- 0.66 and 6.58 +/- 0.68 micrograms/l, respectively).. These results indicate that thyroid hormone may play an important role in the appropriate secretion of leptin in humans.

Topics: Adult; Analysis of Variance; Body Mass Index; Female; Humans; Hyperthyroidism; Hypothyroidism; Leptin; Proteins; Regression Analysis

Leptin, the product of the ob gene, is an important circulating signal for the regulation of body weight. In the present study the role of immunoreactive leptin (leptin-IR) was investigated in functional thyroid disease. Serum leptin-IR levels of 23 hypothyroid and 19 hyperthyroid patients were compared with 21 controls. Leptin-IR was quantified by a specific RIA. In hyperthyroid patients, leptin-IR was not different from controls. Serum leptin-IR levels were significantly increased in hypothyroid patients (21.0 +/- 2.7 micrograms/l vs controls 10.8 +/- 2.1 micrograms/l, P = 0.0044). When serum leptin of hypothyroid patients was compared with euthyroid controls of the same body mass index the difference was still significant (P = 0.0333 by paired Student's t-test). This might indicate that elevation of the serum leptin level does not merely reflect changes in body weight secondary to hypothyroidism, but might be increased to overcome the gain of body weight caused by hypothyroidism.

Topics: Body Mass Index; Female; Humans; Hyperthyroidism; Hypothyroidism; Leptin; Male; Middle Aged; Proteins; Radioimmunoassay

Leptin, the product of the adipose specific ob gene, regulates food intake and energy expenditure. However, little is known about the effects of thyroid status on plasma leptin levels in women. We determined fasting plasma leptin levels before and 1 month after restoration of euthyroidism in 20 female patients with hypothyroidism, 20 female patients with hyperthyroidism and 20 age and BMI-matched female controls. To restore the normal thyroid function patients with hypothyroidism were treated with levothyroxine, whereas patients with hyperthyroidism were treated with propylthiouracil. Plasma leptin levels were measured by a RIA method with a sensitivity of 0.5 microgram/l. Leptin levels were significantly lower in patients with hypothyroidism before treatment (4.17 +/- 2.58 micrograms/l) than in patients with hyperthyroidism (6.80 +/- 4.3 micrograms/l; z = -2.06, p = 0.037). Leptin levels were significantly higher in hyperthyroid patients than in the control group (3.71 +/- 1.69 micrograms/l, z = -2.44, p = 0.014) whereas leptin levels in the hypothyroid patients were not significantly different from those in control subjects (z = -0.16, p = 0.87). Restoration of euthyroid state was not associated with a significant change in leptin levels either in the hypothyroid (from 4.17 +/- 2.58 to 5.22 +/- 3.4 micrograms/l; z = -1.74, p = 0.08) or in the hyperthyroid group (from 6.80 +/- 4.37 micrograms/l to 7.93 +/- 6.25 micrograms/l z = -0.89, p = 0.37), although a tendency for leptin to increase was observed in both groups. There was no correlation between plasma leptin and FT3, FT4, TSH, or BMI either before or after therapy in both groups. Leptin levels were significantly correlated with BMI in the control group (r = -0.53, p = 0.018). We conclude that plasma leptin levels are increased in hyperthyroidism and unchanged in hypothyroidism. Furthermore, our study demonstrates that mean plasma leptin levels are not influenced by short term restoration of euthyroidism in both hypothyroidism and hyperthyroidism, although an effect of long-term treatment may not be excluded.

Topics: Adult; Body Mass Index; Fasting; Female; Humans; Hyperthyroidism; Hypothyroidism; Leptin; Propylthiouracil; Proteins; Thyroid Hormones; Thyroxine

Leptin is an adipose tissue hormone whose plasma levels reflect energy stores. Although pathological thyroid function is related to changes in energy expenditure and body composition, its possible influence on leptin levels remains to be determined. The objective of the study was to provide new data on the relationship between plasma leptin levels and thyroid function. Sixteen patients with primary autoimmune hypothyroidism, and seventeen patients with primary autoimmune hyperthyroidism were prospectively studied from the time of clinical diagnosis and then every 6-8 weeks until thyroid function was completely restored (plasma tri-iodothyronine, free thyroxine and TSH within normal ranges). Fasting immunoreactive plasma leptin levels and body composition (bioelectrical impedance) were assessed at every visit. Plasma leptin levels were correlated with percentage body fat, as previously described, both at the time of diagnosis (r=0.60, P<0.001) and after normalisation of thyroid function (r=0.63, P< 0.001). There was no correlation between serum leptin and thyroid hormone levels at any time during the study. Plasma leptin levels as well as percentage body fat (BF) did not change significantly from the beginning until the end of the study, either in the hypothyroid (leptin: 14.54+/-2.61 vs 16.92+/-2.61 ng/ml, BF: 25.25+/-2.47 vs 25.90+/-3.22%) or in the hyperthyroid (leptin: 10.69+/-1.81 vs 12.36+/-2.19 ng/ml, BF: 22.01+/-2.31 vs 25.39+/-1.13%) group of patients. In conclusion, these results suggest that thyroid function per se is not a major determinant of plasma leptin levels.

Topics: Aged; Autoimmune Diseases; Body Mass Index; Female; Humans; Hyperthyroidism; Hypothyroidism; Leptin; Male; Proteins; Regression Analysis; Thyroid Hormones; Thyrotropin; Thyroxine; Triiodothyronine

To study interactions between leptin and the pituitary-thyroid axis, both in euthyroid and dysthyroid states.. We investigated the relationships of plasma leptin to levels of free thyroid hormones and TSH in 18 patients with newly diagnosed hyperthyroidism, 22 with newly diagnosed primary hypothyroidism, and 32 lean (body mass index [BMI] < 30) and 37 obese (BMI > 30 kg/m2) euthyroid subjects. Hypothyroid patients were restudied during thyroxine replacement treatment.. Median [interquartile range] plasma leptin concentrations were highest in obese euthyroid subjects (31.5 [19.0-48.0] and in untreated hypothyroid patients (19.2 [11.5-31.5]), and lowest levels in untreated hyperthyroid patients (8.9 [5.5-11.1]) and lean euthyroid control subjects (6.6 [3.9-14.4] micrograms/l (Kruskall-Wallis one-way analysis of variance; P < 0.0001). In euthyroid subjects, plasma leptin levels were higher in obese than in lean subjects (P < 0.00001). In obese subjects plasma levels of TSH correlated with percentage body fat (r = 0.67; P < 0.001) and plasma leptin (r = 0.61; P < 0.001). In untreated hyperthyroid subjects plasma leptin was unrelated to free T3, and in untreated hypothyroidism plasma leptin was unrelated to either free T3 or TSH concentrations (all P = NS). In untreated hyperthyroid, but not hypothyroid, patients plasma leptin concentrations correlated with BMI (r = 0.57; P = 0.02). Treatment of hypothyroidism with thyroxine resulted in a significant reduction in plasma leptin concentrations from 20.8 (11.8 to 31.6) to 12.9 (4.6-21.2) micrograms/l (P = 0.005), but BMI did not change significantly in the hypothyroid subjects being studied prospectively.. (i) In euthyroid subjects, plasma leptin and TSH levels correlate, and both are positively correlated with adiposity. (ii) Plasma leptin was significantly elevated in hypothyroid subjects, to levels similar to those seen in obese euthyroid subjects. (iii) Treatment of hypothyroidism resulted in a reduction in the raised plasma leptin levels. The data are consistent with the hypothesis that leptin and the pituitary-thyroid axis interact in the euthyroid state, and that hypothyroidism reversibly increases leptin concentrations.

Topics: Adult; Analysis of Variance; Body Mass Index; Female; Humans; Hyperthyroidism; Hypothyroidism; Leptin; Male; Middle Aged; Obesity; Pituitary Gland; Proteins; Thyroid Diseases; Thyroid Gland; Thyrotropin; Thyroxine; Triiodothyronine

Leptin, a 16-kDa adipocyte-derived protein whose circulating levels reflect energy stores, increases the resting metabolic rate and thermogenesis in rodents. Thyroid hormones also increase the basal metabolic rate, but nothing is known about possible interactions between leptin and thyroid hormone. Activation of beta-adrenergic receptors decreases leptin levels in rodents. To test the hypothesis that thyroid hormones, by causing a "functional hyperadrenergic" state, result in decreased leptin concentrations in humans, we studied 22 normal healthy men before and after the administration of T3 for 1 week to induce moderate hyperthyroidism. Short term thyroid hormone excess does not alter circulating leptin concentrations despite a demonstrated effect on heart rate, systolic blood pressure, cholesterol levels, and metabolic indexes of bone turnover. Elucidation of the apparently separate pathways by which thyroid hormones, beta-agonists, and leptin regulate energy expenditure and food intake may have important implications for our understanding of the mechanisms for regulating energy homeostasis in health and disease.

Topics: Adolescent; Adult; Blood Pressure; Bone and Bones; Cholesterol; Heart Rate; Humans; Hyperthyroidism; Leptin; Male; Proteins; Thyroid Hormones; Triiodothyronine

Leptin, the product of the ob gene, is a recently discovered hormone secreted by adipocytes. Serum leptin concentrations increase in correlation with the percentage of body fat, but besides that, little is known about the physiological actions of leptin in humans. The aim of this study was to assess the influence of hypo- and hyperthyroidism on serum leptin levels. Thirty-two patients (16 with hypothyroidism and 16 with hyperthyroidism) were studied before and after treatment with replacement doses of T4 (hypothyroid patients) or methimazole (hyperthyroid), when thyroid function was normal. Control serum for each group was obtained from healthy age-, sex-, and body mass index-matched subjects. Plasma leptin levels were measured by specific RIA. The mean leptin level in the hypothyroid patients was lower before treatment (4.7 +/- 0.7 microg/L) than that in the controls (8.6 +/- 1.4 microg/L; P < 0.02) and was lower than that during treatment with T4 and normalization of thyroid function in the same group of patients (6.3 +/- 0.8 microg/L; P < 0.05). Leptin levels in the hyperthyroid patients were similar before (7.2 +.0 1.1 microg/L) and after normalization of thyroid function following treatment with methimazole (6.2 +/- 1.1 microg/L) and were similar to the control value (8.8 +/- 1.4 microg/L). In conclusion, leptin levels are decreased in the hypothyroid patients and unchanged in hyperthyroidism. Whether decreased leptin levels may contribute to the decreased energy expenditure in patients with hypothyroidism merits further investigation.

Topics: Female; Humans; Hyperthyroidism; Hypothyroidism; Leptin; Male; Methimazole; Proteins; Thyroxine

Leptin, the product of the ob gene, is secreted by adipocytes and has been shown to decrease appetite and increase energy expenditure. Leptin mRNA in adipocytes correlates with body wt, and serum leptin levels correlate with body fat. Alterations in thyroid status are frequently associated with changes in body wt. To evaluate the possible influence of thyroid status on the leptin system, we have measured serum leptin concentrations in thyroidectomized rats infused either with placebo, or with different doses of T4 (0.8 to 8.0 microg/100 g body wt per day) or T3 (0.25 to 2.0 microg/100 g body wt per day), covering a wide range of thyroid hormone concentrations, from overt hypothyroidism to hyperthyroidism. Intact animals infused with placebo were used as euthyroid controls. Infusion of T4 or T3 into thyroidectomized rats resulted in a decrease in serum leptin levels with respect to the thyroidectomized animals infused with placebo. When compared to the control group, serum leptin levels were decreased in the groups infused with the higher T4 and T3 doses, and tended to be elevated in the thyroidectomized animals infused with placebo. The leptin/body wt ratio was markedly increased in thyroidectomized rats infused with placebo, and decreased in the animals infused with the higher thyroid hormone doses. In conclusion, thyroid hormones exert a negative influence on serum leptin concentrations, which is greater than expected by the changes in body wt The precise mechanism of this influence remains to be elucidated.

Topics: Analysis of Variance; Animals; Body Weight; Dose-Response Relationship, Drug; Female; Hyperthyroidism; Hypothyroidism; Leptin; Proteins; Rats; Rats, Wistar; Thyroid Gland; Thyroid Hormones; Thyroidectomy; Thyrotropin; Thyroxine; Triiodothyronine