neuropeptide-y and Hypothyroidism

To illustrate the role of neuropeptide Y (NPY), agouti-related-peptide (AgRp) and their ratio in patients with primary hypothyroidism (PHT) regarding the effect of levothyroxine (LT4) replacement therapy.. The case-control study was conducted at the Department of Pharmacology, College of Medicine, Mustansiriya University, Baghdad, Iraq, from March to June, 2020 and involved 40 patients with primary hypothyroidism (PHT), including 20 newly diagnosed patients and 20 patients on levothyroxine (LT4) replacement therapy compared to 20 healthy controls. Anthropometric, lipid and pressure profiles were evaluated. Also T3, T4, TSH, NPY and AgRp serum level were estimated in different treated groups. SPSS version 20.00 was used for data analysis.. Body mass index (BMI) was higher in the newly diagnosed patients without thyroxine therapy as compared to patients on thyroxine therapy (P=0.03). Blood pressure profile was higher in patients with PHT compared to the controls (P=0.0001). NPY serum level was lower in patients with PHT without thyroxine therapy (27.32±10.30ng/dL) as compared to patients with PHT on thyroxine therapy (61.10±22.78ng/dL), (P=0.04). AgRP serum level was lower in patients with PHT (9.81±4.86ng/dL) as compared to the patients on the thyroxine therapy (28.99±2.16ng/dL), (P=0.03). Besides, NPY-AgRP ratio (NAR) was higher in patients with PHT (2.78±0.14) as compared to patients with PHT on thyroxine therapy (2.10±0.19), (P=0.0001).. Both of NPY and AgRP serum levels are reduced in the newly diagnosed patients with PHT and ameliorated following LT4 replacement therapy. Also NPY/AgRP ratio is linked with early PHT and regarded as a prognostic value for the outcomes of patients with PHT.

Topics: Agouti Signaling Protein; Case-Control Studies; Humans; Hypothyroidism; Neuropeptide Y; Thyroxine

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

Thyroid hormone and leptin are essential regulators of energy homeostasis. Both hormones stimulate energy expenditure but have opposite effects on appetite. The mechanisms behind food intake regulation in thyroid dysfunctions are poorly understood. It has been shown that hypothyroid rats exhibited impaired leptin anorexigenic effect and signaling in total hypothalamus, even though they were hypophagic. It was hypothesized that hypothyroidism modulates the expression of neuropeptides: orexigenic neuropeptide Y (NPY) and anorexigenic proopiomelanocortin (POMC), independently of inducing nuclei-specific changes in hypothalamic leptin signaling.. Adult male rats were rendered hypothyroid by administration of 0.03% methimazole in the drinking water for 21 days. Protein content of NPY, POMC, and leptin signaling (the signal transducer and activator of transcription 3 [STAT3] pathway) were evaluated by Western blot, and mRNA levels by real time reverse transcription polymerase chain reaction in arcuate (ARC), ventromedial (VMN), and paraventricular (PVN) hypothalamic nuclei isolated from euthyroid (eu) and hypothyroid (hypo) rats. Leptin anorexigenic effect was tested by recording food intake for two hours after intracerebroventricular (i.c.v.) administration of leptin. Statistical differences were considered significant at p ≤ 0.05.. Hypothyroidism was confirmed by decreased serum triiodothyronine, thyroxine, and increased thyrotropin, in addition to increased levels of pro-TRH mRNA in PVN and Dio2 mRNA in the ARC of hypo rats. Hypothyroidism decreased body weight and food intake associated with decreased protein content of NPY and increased content of POMC in the ARC. Conversely, hypothyroidism induced central resistance to the acute anorexigenic effect of leptin, since while euthyroid rats displayed reduced food intake after leptin i.c.v. injection, hypothyroid rats showed no response. Hypothyroid rats exhibited decreased leptin receptor (ObRb) protein content in ARC and VMN but not in PVN nucleus. ObRb protein changes were concomitant with decreased phosphorylated STAT3 in the ARC, and decreased total STAT3 in VMN and PVN. However, hypothyroidism did not affect mRNA levels of Lepr or Stat3 in the hypothalamic nuclei.. Experimental hypothyroidism induced a negative energy balance accompanied by decreased NPY and increased POMC protein content in the ARC, resulting in predominance of anorexigenic pathways, despite central leptin resistance and impairment of the leptin signaling cascade in a nuclei-specific manner.

Topics: Animals; Appetite Regulation; Arcuate Nucleus of Hypothalamus; Disease Models, Animal; Eating; Energy Metabolism; Feeding Behavior; Hypothyroidism; Iodide Peroxidase; Iodothyronine Deiodinase Type II; Leptin; Male; Methimazole; Neuropeptide Y; Paraventricular Hypothalamic Nucleus; Phosphorylation; Pro-Opiomelanocortin; Rats, Wistar; Receptors, Leptin; Signal Transduction; STAT3 Transcription Factor; Thyrotropin-Releasing Hormone; Ventromedial Hypothalamic Nucleus; Weight Loss

Fifteen years ago orexins were identified as central regulators of energy homeostasis. Since then, that concept has evolved considerably and orexins are currently considered, besides orexigenic neuropeptides, key modulators of sleep-wake cycle and neuroendocrine function. Little is known, however, about the effect of the neuroendocrine milieu on orexins' effects on energy balance. We therefore investigated whether hypothalamic-pituitary axes have a role in the central orexigenic action of orexin A (OX-A) by centrally injecting hypophysectomized, adrenalectomized, gonadectomized (male and female), hypothyroid, and GH-deficient dwarf rats with OX-A. Our data showed that the orexigenic effect of OX-A is fully maintained in adrenalectomized and gonadectomized (females and males) rats, slightly reduced in hypothyroid rats, and totally abolished in hypophysectomized and dwarf rats when compared with their respective vehicle-treated controls. Of note, loss of the OX-A effect on feeding was associated with a blunted OX-A-induced increase in the expression of either neuropeptide Y or its putative regulator, the transcription factor cAMP response-element binding protein, as well as its phosphorylated form, in the arcuate nucleus of the hypothalamus of hypophysectomized and dwarf rats. Overall, this evidence suggests that the orexigenic action of OX-A depends on an intact GH axis and that this neuroendocrine feedback loop may be of interest in the understanding of orexins action on energy balance and GH deficiency.

Topics: Adrenalectomy; Animals; Appetite Regulation; Castration; Cyclic AMP Response Element-Binding Protein; Dwarfism, Pituitary; Feeding Behavior; Female; Growth Hormone; Hypophysectomy; Hypothalamus; Hypothyroidism; Injections, Intraventricular; Intracellular Signaling Peptides and Proteins; Male; Neurons; Neuropeptide Y; Neuropeptides; Orexins; Pituitary Gland; Rats; Rats, Inbred Lew; Rats, Sprague-Dawley; Receptors, Somatotropin

It has been postulated that a cold-induced decrease in hypothalamic neuropeptide Y (NPY) might disinhibit the sympathetic outflow that activates brown adipose tissue (BAT) thermogenesis. The present work has assessed the interscapular BAT NPY and norepinephrine (NE) concentrations 7 days after surgical excision of the sympathetic nerves (Sx) of each BAT lobe in rats exposed to 4 degrees C or 24 degrees C during 24 h. In addition, the effects of NPY treatment on BAT oxygen (O2) consumption in normal and T3-treated hypothyroid rats was determined. Sprague-Dawley rats weighing 220-240 g were used. BAT was removed and homogenized in 0.1 M HCl. BAT NPY content at 24 degrees C was 109 +/- 19 pg/mg protein. Sx decreased this value significantly (P < 0.001) and cold increased it by two-fold (P < 0.001). Neither cold nor Sx altered hypothalamic NPY. BAT O2 consumption was depressed by NPY treatment (P < 0.001) and increased by NE (P < 0.001). In euthyroid Sx rats, NPY decreased O2 consumption (P < 0.001). NPY failed to alter O2 consumption in hypothyroid rats and sharply decreased it in T3-treated rats. The results show that NPY blocked the effects of T3 on BAT O2 consumption, and that cold-induced activation of the thermogenic process did not produce measurable changes in hypothalamic NPY.

Topics: Adipose Tissue, Brown; Animals; Cold Temperature; Hypothyroidism; Iodine Radioisotopes; Mitochondria; Neuropeptide Y; Norepinephrine; Oxygen Consumption; Rats; Rats, Sprague-Dawley; Sympathetic Nervous System; Triiodothyronine

We examined whether hypothyroidism-induced increases in the anterior pituitary content of vasoactive intestinal peptide (VIP) and neuropeptide Y (NPY) are mediated by the hypothalamus. Male Sprague-Dawley rats were anesthetized and one of the following surgeries was performed: (1) sham thyroidectomy, (2) thyroidectomy, (3) thyroidectomy plus surgical anterolateral deafferentation of the medial basal hypothalamus, or (4) thyroidectomy and sham deafferentation of the hypothalamus (knife was inserted but not rotated). Two weeks after surgery, animals were killed and tissue samples collected for measurement of the anterior pituitary VIP and NPY and plasma thyroid-stimulating hormone (TSH), thyroxine, and prolactin concentrations (by RIA). Reverse-phase HPLC showed that VIP and NPY immunoreactivities in the anterior pituitary extracts are eluted in the positions identical to synthetic VIP and NPY, respectively. Only data from those animals with complete symmetric cuts located at the posterior border of the optic chiasm were included for analysis. In the thyroidectomized rats the anterior pituitary contents of VIP and NPY were significantly increased. These responses were almost completely prevented by the anterolateral deafferentation of the hypothalamus. Sham hypothalamic deafferentation had no effect on the pituitary neuropeptide responses to hypothyroidism. Anterolateral deafferentation of the hypothalamus also significantly blunted plasma TSH responses to hypothyroidism. These data suggest that some hypothalamic factor is involved in the mediation of the effect of hypothyroidism on the pituitary content of VIP and NPY.

Topics: Afferent Pathways; Animals; Chromatography, High Pressure Liquid; Denervation; Hypothalamic Area, Lateral; Hypothyroidism; Male; Neuropeptide Y; Organ Size; Pituitary Gland, Anterior; Rats; Rats, Sprague-Dawley; Thyroid Gland; Thyrotropin; Vasoactive Intestinal Peptide