pituitrin and Obesity

The neurohypophysial endocrine system is identified here as a potential target for therapeutic interventions toward improving obesity-related metabolic dysfunction, given its coinciding pleiotropic effects on psychological, neurological and metabolic systems that are disrupted in obesity.. Copeptin, the C-terminal portion of the precursor of arginine-vasopressin, is positively associated with body mass index and risk of type 2 diabetes. Plasma oxytocin is decreased in obesity and several other conditions of abnormal glucose homeostasis. Recent data also show non-classical tissues, such as myocytes, hepatocytes and β-cells, exhibit responses to oxytocin and vasopressin receptor binding that may contribute to alterations in metabolic function. The modulation of anorexigenic and orexigenic pathways appears to be the dominant mechanism underlying the effects of oxytocin and vasopressin on body weight regulation; however, there are apparent limitations associated with their use in direct pharmacological applications. A clearer picture of their wider physiological effects is needed before either system can be considered for therapeutic use.

Topics: Animals; Blood Glucose; Body Mass Index; Body Weight; Diabetes Mellitus, Type 2; Eating; Energy Metabolism; Gastrointestinal Microbiome; Glucose; Hepatocytes; Homeostasis; Humans; Insulin Resistance; Lipid Metabolism; Muscle Cells; Obesity; Oxytocin; Vasopressins

Vasopressin has many physiological actions in addition to its well-defined role in the control of fluid homeostasis and urine concentration. An increasing body of evidence suggests that the vasopressin-hydration axis plays a role in glucose homeostasis. This review summarizes the knowledge accumulated over the last decades about the influence of vasopressin in the short-term regulation of glycaemia. It describes the possible role of this hormone through activation of V1a and V1b receptors on liver and pancreas functions and on the hypothalamic-pituitary-adrenal axis. Moreover, we report recent in vivo studies demonstrating the role of vasopressin in the long-term regulation of glycaemia. Indeed, V1a- or double-V1aV1b-receptor knockout mice display significant changes in the glucose and lipid metabolism. In rats, sustained high V1aR activation increases basal glycaemia and aggravates glucose intolerance in obese rats. Finally, the translation from animal findings to human was evidenced by epidemiological and genetic studies that showed that high vasopressin level is a risk factor for hyperglycaemia, metabolic disorders and diabetes.

Topics: Animals; Blood Glucose; Glucose; Glycopeptides; Homeostasis; Humans; Metabolic Diseases; Obesity; Rats; Receptors, Vasopressin; Vasopressins

Cushing's syndrome is a consequence of primary or, more commonly, secondary oversecretion of cortisol. Cardiovascular disease is the major cause of morbidity and mortality in Cushing's syndrome, and excess risk remains even in effectively treated patients. The cardiovascular consequences of cortisol excess are protean and include, inter alia, elevation of blood pressure, truncal obesity, hyperinsulinemia, hyperglycemia, insulin resistance, and dyslipidemia. This review analyses the relationship of cortisol excess, both locally and at tissue level, to these cardiovascular risk factors, and to putative mechanisms for hypertension. Previous studies have examined correlations between cortisol, blood pressure, and other parameters in the general population and in Cushing's syndrome. This review also details changes induced by short-term cortisol administration in normotensive healthy men.

Topics: Blood Pressure; Cardiac Output; Cardiovascular Diseases; Cushing Syndrome; Female; Humans; Hydrocortisone; Hyperglycemia; Hyperlipidemias; Hypertension; Insulin Resistance; Male; Obesity; Plasma Volume; Renin-Angiotensin System; Risk Factors; Sympathetic Nervous System; Vascular Resistance; Vasodilation; Vasopressins

Dopamine, a neurotransmitter, precursor of noradrenaline, is responsible for cardiovascular and renal actions, such as increase in myocardial contractility and cardiac output, without changes in heart rate, producing passive and active vasodilatation, diuresis and natriuresis. These cardiovascular and renal actions take place through the interaction with dopamine receptors, D(1), D(2), D(3), D(4), and D(5). Recent findings point to the possibility of D(6) and D(7)receptors. Dopamine is known to influence the control of arterial pressure by influencing the central and peripheral nervous system and target organs such as kidneys and adrenal glands, in some types of hypertension. Although dopamine and its derivatives have been shown to have antihypertensive effects, these are still being studied; therefore it is important to explain some physiological and pharmacological aspects of dopamine, its receptors, and the clinical uses it could have in the treatment of arterial hypertension and more recently in obesity, based on evidence proving a clear association between obesity and the decrease in the expression of D(2) receptors in the brain of obese persons.

Topics: Angiotensin II; Animals; Dopamine; Dopamine Agonists; Humans; Hypertension; Nitric Oxide; Obesity; Protein Kinase C; Rats; Receptors, Dopamine; Risk Factors; Sodium-Hydrogen Exchangers; Vasopressins

The association between alcohol intake and blood pressure has been known for nearly 70 years. It was postulated that the alcohol blood pressure association was not causal but linked to common factors such as stress, obesity or salt intake. Recently large population studies have shown that the association is independent of these factors. Alcohol dependent persons have a high incidence of hypertension which is a common clinical problem. It is probably due to alcohol withdrawal and is mediated via increased cortisol and catecholamine production. Alcohol has also a direct effect causing arteriolar vasoconstriction. This direct effect may result from an alcohol associated alteration of intracellular Ca in arteriolar smooth muscle leading to supersensitivity to circulating pressor agents.

Topics: Arteries; Ethanol; Hemodynamics; Humans; Hydrocortisone; Hypertension; Obesity; Renin-Angiotensin System; Sodium; Stress, Psychological; Substance Withdrawal Syndrome; Sympathetic Nervous System; Vasopressins; Water

Topics: Adrenocorticotropic Hormone; Diabetes Mellitus; Dose-Response Relationship, Drug; Drug Resistance; Endocrine System Diseases; Gonadotropins; Hormones; Humans; Insulin Resistance; Neuromuscular Diseases; Obesity; Parathyroid Hormone; Receptor, Insulin; Receptors, Cell Surface; Syndrome; Thyrotropin; Vasopressins

Topics: Angiotensins; Catecholamines; Diabetes Mellitus; Hemorrhage; Hormones; Humans; Liver; Obesity; Phosphorylases; Shock; Vasopressins

Topics: 17-Hydroxycorticosteroids; Adrenal Cortex; Adrenal Glands; Adrenocorticotropic Hormone; Anorexia Nervosa; Blood Glucose; Brain Diseases; Catecholamines; Child; Circadian Rhythm; Cyproterone; Dexamethasone; Growth Hormone; Humans; Hydrocortisone; Hypoglycemia; Hypothalamus; Infant; Insulin; Metyrapone; Nephrotic Syndrome; Obesity; Pituitary Gland; Prednisone; Vasopressins

Topics: Adrenal Gland Diseases; Adrenal Glands; Adrenalectomy; Cushing Syndrome; Dexamethasone; Diagnosis, Differential; Humans; Hydrocortisone; Hyperaldosteronism; Hypertension; Hypokalemia; Kidney; Obesity; Pituitary-Adrenal Function Tests; Pituitary-Adrenal System; Vasopressins

Topics: Abdomen; Aged; Crohn Disease; Duodenal Diseases; Duodenal Ulcer; Esophageal Achalasia; Esophagitis; Follow-Up Studies; Gastrectomy; Gastritis; Gastrointestinal Hemorrhage; Hematoma; Hernia, Diaphragmatic; Humans; Intestine, Small; Methods; Obesity; Peptic Ulcer Hemorrhage; Postoperative Complications; Stomach Neoplasms; Stomach Ulcer; Vagotomy; Vasopressins; Zollinger-Ellison Syndrome

Topics: Bile; Biliary Tract Diseases; Cholelithiasis; Cholesterol; Gastric Juice; Gastrointestinal Diseases; Gastrointestinal Hemorrhage; Humans; Obesity; Peptic Ulcer; Phosphatidylcholines; Pylorus; Research; Stress, Physiological; Urinary Diversion; Vagotomy; Vasopressins; Vitamin A

Topics: Adrenocorticotropic Hormone; Anatomy; Follicle Stimulating Hormone; Gonadotropins, Pituitary; Growth Hormone; Humans; Hypothalamus; Luteinizing Hormone; Obesity; Oxytocin; Physiology; Pituitary Gland; Pituitary Hormones; Pituitary Hormones, Anterior; Pituitary Hormones, Posterior; Prolactin; Thyrotropin; Vasopressins

Topics: Adrenal Glands; Aldosterone; Angiotensins; Arteriosclerosis; Autonomic Nervous System Diseases; Catecholamines; Chromosome Aberrations; Essential Hypertension; Hypertension; Metabolism; Nephrectomy; Obesity; Sodium; Thyroid Gland; Vasopressins; Water-Electrolyte Balance

Arginine vasopressin (AVP) and prolactin (PRL) concentrations were measured in the plasma of grossly obese subjects to determine if abnormalities in salt and water homeostasis could be related to these hormones. Acute oral water loads and hypertonic saline infusions were administered during baseline obesity, after prolonged fasting, and after hypocaloric refeeding. Only 64.7%, 46.1%, and 70.1% of a water load was excreted during the respective three stages. Pre-water load plasma AVP levels were normal, but after the water load the obese failed to suppress AVP secretion in a normal fashion; this defect was corrected after fasting and with refeeding. Salt loading resulted in appropriate osmolality and AVP responses. Serum prolactin levels, normal at baseline during all phases, rose slightly after water loading during fasting. Hypertonic.saline produced no changes in prolactin levels in the obese or in the normal controls. In the disordered salt and water metabolism of the obese, persistently high AVP values during water loading appeared to be a factor in the delay of water excretion. In the observed water retentionduring dietary restriction and refeeding, secretion of AVP and PRL did not appear to have a major regulatory function.

Topics: Adult; Clinical Trials as Topic; Eating; Fasting; Humans; Male; Obesity; Prolactin; Sodium Chloride; Vasopressins; Water; Water-Electrolyte Balance

No clear association between standard vasopressin doses and body mass index exists, despite potential pharmacokinetic and pharmacodynamic variability among patients with septic shock. It is unknown if higher doses may alter hemodynamic response.. The purpose of this study was to evaluate the effect of vasopressin dose on hemodynamic response in obese patients with septic shock.. A single-center, retrospective cohort study was conducted in adult, obese patients with septic shock receiving catecholamine vasopressors and vasopressin. Patients were analyzed according to vasopressin dose received: standard dose (≤0.04 U/min) and high dose (>0.04 U/min). The primary outcome was percentage change in norepinephrine equivalent (NEQ) dose.. A total of 182 patients were included in the analysis, with 136 in the standard-dose vasopressin group and 46 in the high-dose vasopressin group. There was no difference in percentage change in NEQ dose at 6 hours after standard- or high-dose vasopressin attainment (-28.6% vs -19.1%;. This represents the first analysis comparing standard and higher doses of vasopressin in obese patients with septic shock. Receipt of high-dose vasopressin was not associated with a difference in catecholamine requirement or improved outcomes. Further studies are warranted to provide guidance on the use of high-dose vasopressin in septic shock.

Topics: Adult; Hemodynamics; Humans; Norepinephrine; Obesity; Retrospective Studies; Shock, Septic; Vasoconstrictor Agents; Vasopressins

Nesfatin-1, processed from nucleobindin-2 (NUCB2), is a potent anorexigenic peptide being expressed in rodent hypothalamic nuclei and involved in the regulation of feeding behavior and body weight in animals. The present study aimed to investigate NUCB2/nesfatin-1 protein expression in the human hypothalamus as well as its correlation with body weight.. Sections of hypothalamus and adjacent cholinergic basal forebrain nuclei, including the nucleus basalis of Meynert (NBM) and the diagonal band of Broca (DBB), from 25 autopsy cases (17 males, 8 females; 8 lean, 9 overweight, 8 obese) were examined using immunohistochemistry and double immunofluorescence labeling.. Prominent NUCB2/nesfatin-1 immunoexpression was detected in supraoptic, paraventricular, and infundibular nuclei, lateral hypothalamic area (LHA)/perifornical region, and NBM/DBB. NUCB2/nesfatin-1 was found to extensively colocalize with (a) oxytocin and vasopressin in paraventricular and supraoptic nuclei, (b) melanin-concentrating hormone in the LHA, and (c) cocaine- and amphetamine-regulated transcript in infundibular and paraventricular nuclei and LHA. Interestingly, in the LHA, NUCB2/nesfatin-1 protein expression was significantly decreased in obese, compared with lean (p < 0.01) and overweight (p < 0.05) subjects.. The findings of the present study are suggestive of a potential role for NUCB2/nesfatin-1 as an integral regulator of food intake and energy homeostasis in the human hypothalamus. In the LHA, an appetite- and reward-related brain area, reduced NUCB2/nesfatin-1 immunoexpression may contribute to dysregulation of homeostatic and/or hedonic feeding behavior and obesity. NUCB2/nesfatin-1 localization in NBM/DBB might imply its participation in the neuronal circuitry controlling cognitive influences on food intake and give impetus towards unraveling additional biological actions of NUCB2/nesfatin-1 in human neuronal networks.

Topics: Adult; Aged; Aged, 80 and over; Body Weight; Case-Control Studies; Female; Humans; Hypothalamic Hormones; Hypothalamus; Male; Melanins; Middle Aged; Nerve Tissue Proteins; Nucleobindins; Obesity; Oxytocin; Pituitary Hormones; Vasopressins

The oxytocin (OT) and vasopressin (VP) neurons of the supraoptic nucleus (SON) demonstrate characteristics of "metabolic sensors". They express insulin receptors and glucokinase (GK). They respond to an increase in glucose and insulin with an increase in intracellular [Ca(2+)] and increased OT and VP release that is GK dependent. Although this is consistent with the established role of OT as an anorectic agent, how these molecules function relative to the important role of OT during lactation and whether deficits in this metabolic sensor function contribute to obesity remain to be examined. Thus, we evaluated whether insulin and glucose-induced OT and VP secretion from perifused explants of the hypothalamo-neurohypophyseal system are altered during lactation and by diet-induced obesity (DIO). In explants from female day 8 lactating rats, increasing glucose (Glu, 5 mM) did not alter OT or VP release. However, insulin (Ins; 3 ng/ml) increased OT release, and increasing the glucose concentration in the presence of insulin (Ins+Glu) resulted in a sustained elevation in both OT and VP release that was not prevented by alloxan, a GK inhibitor. Explants from male DIO rats also responded to Ins+Glu with an increase in OT and VP regardless of whether obesity had been induced by feeding a high-fat diet (HFD). The HFD-DIO rats had elevated body weight, plasma Ins, Glu, leptin, and triglycerides. These findings suggest that the role of SON neurons as metabolic sensors is diminished during lactation, but not in this animal model of obesity.

Topics: Alloxan; Animals; Dehydration; Diet, High-Fat; Dietary Fats; Enzyme Inhibitors; Female; Glucokinase; Glucose; In Vitro Techniques; Insulin; Lactation; Neurons; Obesity; Oxytocin; Rats; Rats, Sprague-Dawley; Receptor, Insulin; Supraoptic Nucleus; Vasopressins

Fixed-dose vasopressin is an adjunctive therapy to norepinephrine (NE) to raise mean arterial pressure (MAP) and decrease NE requirements in patients with septic shock. It is unknown if weight affects hemodynamic response to vasopressin or if a weight-based vasopressin strategy is superior to fixed dosing.. The primary objective was to evaluate effect of body weight on response to vasopressin as measured by change in MAP 1 hour post-vasopressin initiation.. A single-center, retrospective study was performed in patients with septic shock. Baseline characteristics, catecholamine and vasopressin requirement, response to therapy, and adverse events were collected.. Forty patients were included who received a fixed-dose vasopressin in addition to catecholamine infusions. No correlation was found in the primary outcome of change in MAP at 1 hour after vasopressin initiation compared with vasopressin dose relative to patient weight or body mass index (BMI). Change in MAP at 6 and 12 hours was not significant. In the obese population (n = 9), there was a significant negative correlation between BMI and change in MAP at 6 hours (correlation coefficient r = -0.951; P = 0.0009). Linear regression analysis confirmed that vasopressin dose relative toweight was independently associated with change in MAP at 1, 6, and 12 hours, whereas changes in NE dosing were not.. Increasing weight-based dosing of vasopressin did not correlate with change in MAP when used with catecholamine vasopressors in septic shock. However, fixed-dose vasopressin may not be sufficient in obese septic shock patients with a BMI ≥30 kg/m(2).

Topics: Arterial Pressure; Body Mass Index; Body Weight; Dose-Response Relationship, Drug; Female; Hemodynamics; Humans; Infusions, Intravenous; Male; Middle Aged; Norepinephrine; Obesity; Regression Analysis; Retrospective Studies; Shock, Septic; Vasoconstrictor Agents; Vasopressins

High plasma copeptin, a marker of vasopressin (VP) secretion, has been shown to be associated with the metabolic syndrome and development of type 2 diabetes in humans. The present study was designed to determine the long-term influence of plasma VP concentration in a rodent model prone to metabolic dysfunction.. Obese Zucker rats and their lean counterparts were submitted for 4 weeks to one of three protocols inducing different levels of VP. Circulating VP was either reduced by increasing the daily water intake (low-VP), or increased by a chronic i.p. infusion of VP (high-VP). The control rats had normal VP levels that depended on their own regulation of water intake and VP secretion.. Compared with controls with normal VP, lean rats with high-VP had a higher fasting glycaemia after 4 weeks. In obese rats, high-VP promoted hyperinsulinaemia, glucose intolerance, assessed by glucose and insulin tolerance tests, and an impaired response to a pyruvate challenge. Conversely, treatment with a selective arginine vasopressin receptor 1A (V1aR) antagonist reduced glucose intolerance. Low-VP obese rats had unchanged glucose tolerance but exhibited a drastic decrease in liver steatosis compared with control obese rats, associated with low hepatic triacylglycerol and cholesterol content, and reduced expression of hepatic lipogenic genes. These effects were independent of changes in body adiposity, and plasma sodium and osmolality did not differ among groups.. These findings show a causal relationship between the VP-hydration axis and the metabolic risk. Therapeutic perspectives include diet recommendations regarding hydration, but also potential pharmacological interventions targeting the VP V1aR.

Topics: Animals; Antidiuretic Hormone Receptor Antagonists; Blood Glucose; Drinking; Fatty Liver; Glucose Intolerance; Glucose Tolerance Test; Indoles; Male; Obesity; Pyrrolidines; Rats, Zucker; Vasopressins

Behavioral modifications for the treatment of obesity, including caloric restriction, have notoriously low long-term success rates relative to bariatric weight-loss surgery. The reasons for the difference in sustained weight loss are not clear. One possibility is that caloric restriction alone activates the stress-responsive hypothalamo-pituitary-adrenocortical (HPA) axis, undermining the long-term maintenance of weight loss, and that this is abrogated after bariatric surgery. Accordingly, we compared the HPA response to weight loss in five groups of male rats: (1) high-fat diet-induced obese (DIO) rats treated with Roux-en-Y gastric bypass surgery (RYGB, n = 7), (2) DIO rats treated with vertical sleeve gastrectomy (VSG, n = 11), (3) DIO rats given sham surgery and subsequently restricted to the food intake of the VSG/RYGB groups (Pair-fed, n = 11), (4) ad libitum-fed DIO rats given sham surgery (Obese, n = 11) and (5) ad libitum chow-fed rats given sham surgery (Lean, n = 12). Compared with Lean controls, food-restricted rats exhibited elevated morning (nadir) non-stress plasma corticosterone concentration and increased hypothalamic corticotropin-releasing hormone and vasopressin mRNA expression, indicative of basal HPA activation. This was largely prevented when weight loss was achieved by bariatric surgery. DIO increased HPA activation by acute (novel environment) stress and this was diminished by bariatric surgery-, but not pair-feeding-, induced weight loss. These results indicate that the HPA axis is differentially affected by weight loss from caloric restriction versus bariatric surgery, and this may contribute to the differing long-term effectiveness of these two weight-loss approaches.

Topics: Animals; Caloric Restriction; Corticosterone; Corticotropin-Releasing Hormone; Diet, High-Fat; Disease Models, Animal; Gastrectomy; Gastric Bypass; Hypothalamo-Hypophyseal System; Male; Obesity; Pituitary-Adrenal System; Rats, Long-Evans; RNA, Messenger; Stress, Physiological; Time Factors; Vasopressins; Weight Loss

Topics: Animals; Basic Helix-Loop-Helix Transcription Factors; Eating; Hypothalamus; Mice; Mice, Transgenic; Neural Pathways; Neurons; Neurosecretory Systems; Obesity; Oxytocin; Paraventricular Hypothalamic Nucleus; Repressor Proteins; RNA, Messenger; Vasopressins

Adult patients with hypopituitarism are treated by the replacement of deficient hormones, although GH has not been substituted until March 2006 in Japan except for clinical trial. This study examines which hormonal status influences the prevalence of vascular risk disorders in hypopituitary adults. A sample of 263 adult patients with hypopituitarism was studied, among whom there were various hormonal status such as no deficiency, treated or untreated deficiency of each pituitary hormone. Analysis of adult patients with hypopituitarism showed that hypertension was more prevalent in the older than in younger patients and in male than in female patients. Hypercholesterolemia and hypertriglyceridemia were more prevalent in patients with TSH deficiency even with thyroxine substitution than those without TSH deficiency. Both obesity and hypertension were less prevalent in patients with treated ACTH deficiency than those without ACTH deficiency. Obesity was more prevalent in patients with treated vasopressin deficiency than those without vasopressin deficiency. These results provide evidence that glucocorticoid substitution in ACTH deficient adults was favorable to prevent obesity and hypertension but that the thyroxine substitution in TSH deficient adults appeared rather insufficient to prevent hyperlipidemia.

Topics: Adolescent; Adrenocorticotropic Hormone; Adult; Age Distribution; Aged; Aged, 80 and over; Female; Hormone Replacement Therapy; Humans; Hypercholesterolemia; Hypertension; Hypertriglyceridemia; Hypopituitarism; Male; Middle Aged; Obesity; Prevalence; Risk Factors; Sex Distribution; Thyrotropin; Thyroxine; Vascular Diseases; Vasopressins

The dynamic of natural antibodies against angiotensin II, bradykinin and vasopressin in blood serum was studied in 75 patients with hypertension and obesity. Universal normalizing effect of the diet consists in decrease of levels of natural antibodies was found.

Topics: Adult; Angiotensin II; Arteriosclerosis; Bradykinin; Diet, Sodium-Restricted; Female; Humans; Hypertension; Immunoenzyme Techniques; Male; Middle Aged; Obesity; Vasopressins

Co-localization of chemical messengers in the same neuron is linked to neurochemical plasticity and has been studied extensively [B. Meister, M.J. Villar, S. Ceccatelli, T. Hökfelt, Localization of chemical messengers in magnocellular neurons of the hypothalamic supraoptic and paraventricular nuclei: an immunohistochemical study using experimental manipulation, Neuroscience 37 (1990) 603-633; B. Meister, R. Cortés, M.J. Villar, M. Schalling, T. Hökfelt, Peptides and transmitter enzymes in hypothalamic magnocellular neurons after administration of hyperosmotic stimuli: comparison between messenger RNA and peptide/protein levels, Cell Tissue Res. 260 (1990) 279-297]. Obese Zucker rats display an example of such a phenomenon expressing an enzyme of catecholamine synthesis-tyrosine hydroxylase (TH)-in magnocellular neurons (MCN) of supraoptic and paraventricular nuclei of hypothalamus [S. Fetissov, F. Marsais, S. Nicolaïdis, A. Calas, Expression of tyrosine hydroxylase in magnocellular hypothalamic neurons of obese (fa/fa) and lean heterozygous (Fa/fa) Zucker rats, Mol. Brain Res. 50 (1997) 314-318]. To understand the biological role of TH in MCN of obese Zucker rat, we studied TH expression in relation to the vasopressinergic and oxytocinergic neurons. We present a protocol of double labelling including immunohistochemical for TH and in situ hybridization for OT and VP mRNA. The described protocol can be applied for detection of co-localized expressions of a broad range of chemical brain messengers and proteins.

Topics: Animals; Hypothalamus; Immunohistochemistry; In Situ Hybridization; Neurons; Obesity; Oxytocin; Pituitary Gland, Posterior; Rats; Rats, Zucker; RNA, Messenger; Tyrosine 3-Monooxygenase; Vasopressins

To study the regulation of antidiuretic hormone (ADH) and atrial natriuretic peptide (ANP) in obese and lean women with a swelling syndrome.. Thirty-four obese women and 12 lean women with a swelling syndrome and an abnormal isotopic test of capillary permeability to albumin were investigated.. After 10 nocturnal hours of fluid restriction, subjects were asked at 8am to ingest a tap water load of 20 ml/kg within 10 min and to remain strictly recumbent until twelve noon on the first day, and to remain standing and to walk around until twelve noon on the second day. Free water clearance and the cGMP/creatinine and albumin/creatinine ratios were determined hourly in the morning.. The total 4 h-urinary volume/ingested water volume ratio was significantly lower on the second day both in the lean and the obese patients, the differences being slightly larger in the obese patients. The increase in free water clearance was significantly less on the second day in the obese patients. The increase in cGMP/creatinine ratio was also significantly lower on the second day in the obese patients. The maximum level of the urinary albumin/creatinine ratio was significantly higher on the second day in the obese patients.. In obese women with a swelling syndrome: (1) The higher increase in the urinary albumin excretion rate after water loading followed by a sustained upright position suggests a widespread alteration in capillary function, which is also indicated by the isotopic test of capillary permeability to albumin. (2) The water load-induced inhibition of ADH secretion and stimulation of ANP secretion or ANP activity, more defective in the upright position than in the recumbent one, is probably another major contributing factor to orthostatic oedema.

Topics: Adult; Albumins; Atrial Natriuretic Factor; Capillary Permeability; Case-Control Studies; Creatinine; Drinking; Edema; Female; Guanosine Monophosphate; Humans; Middle Aged; Obesity; Posture; Statistics, Nonparametric; Vasopressins

Studies in our laboratory and elsewhere have demonstrated numerous abnormalities of steroid and polypeptide hormone secretion in obesity: hyperestrogenemia and hypogonadotropic hypogonadism in obese men; diminished SHBG levels in both sexes; elevated free testosterone and free estradiol in obese women; PCOS-like gonadotropin and sex-hormone abnormalities in obese women; elevated serum insulin in both sexes; blunted stimulability of prolactin, growth hormone, and vasopressin in both sexes; and elevated basal levels and blunted stimulability and suppressibility of beta-endorphin in both sexes. All of these abnormalities have been clearly shown to be partly or completely reversible with weight loss, with the exception of the endorphin abnormalities. In that area, four out of the five studies reported show no reversibility with weight loss. Reversibility of nearly all the hormonal abnormalities of obesity (i.e., all but the hyperendorphinemia) by weight loss suggests that none of them is causative of obesity. Nevertheless, some of the reversible abnormalities may secondarily amplify the morbidity associated with obesity: the hyperinsulinemia may be related to the increased risk of hypertension, hyperlipidemia, coronary disease, and Type II diabetes; the elevated levels of free estradiol in obese women may be related to their increased risk of breast and endometrial cancer. The role of hyperendorphinemia in obesity clearly requires further investigation, since it is the only observed hormonal abnormality that appears to be non-reversible by weight loss, and also since there seems to be increased sensitivity to beta-endorphin in obesity. The possibility that endorphin abnormalities may be causal in obesity cannot be ruled out.

Topics: Adolescent; Adult; beta-Endorphin; Estradiol; Estrone; Female; Gonadotropins; Hormones; Human Growth Hormone; Humans; Insulin; Male; Middle Aged; Obesity; Prolactin; Sex Hormone-Binding Globulin; Testosterone; Vasopressins

Topics: Animals; Body Weight; Lung; Male; Obesity; Organ Size; Physical Exertion; Radioimmunoassay; Rats; Rats, Sprague-Dawley; Rats, Zucker; Vasopressins

The hormonal control of glycogen synthase and phosphorylase interconversion was investigated in hepatocytes isolated from lean and genetically obese (fa/fa) rats. In cells from obese animals, the inactivation of synthase by 4 beta-phorbol 12 beta-myristate 13 alpha-acetate (PMA), phospholipase C, vasopressin and the alpha 1-adrenergic agonist phenylephrine was markedly impaired, and the property of PMA to counteract phosphorylase activation by phenylephrine was attenuated. The maximal response of phosphorylase activation to phenylephrine and vasopressin was increased in obese-rat hepatocytes, but the sensitivity to these hormones was similar to that in lean-rat hepatocytes. These observations indicate that the defect in protein kinase C that we reported previously in heart of insulin-resistant fa/fa rats [van de Werve, Zaninetti, Lang, Vallotton & Jeanrenaud (1987) Diabetes 36, 310-319] is probably also expressed in liver.

Topics: Animals; Enzyme Activation; Female; Glycogen Synthase; Insulin Resistance; Liver Glycogen; Obesity; Phenylephrine; Phorbol Esters; Phosphorylases; Protein Kinase C; Rats; Stimulation, Chemical; Type C Phospholipases; Vasopressins

We have characterized a plasma membrane phosphatidylinositol 4,5-bisphosphate (PIP2)-specific phospholipase C (PLC) and a cytosolic phosphatidylinositol (PI)-specific PLC in human liver. Epinephrine, 1 x 10(-5) M, and vasopressin, 1 x 10(-8) M, stimulated PIP2-PLC which was enhanced by guanosine 5'-O-(3-thiotriphosphate) (GTP gamma S). PI-PLC stimulation was not observed by these agents. Insulin and insulin-like growth factors (IGF-I and IGF-II) in the presence and absence of GTP gamma S did not stimulate PIP2-PLC or PI-PLC in plasma membranes and cytosol preparations nor phosphoinositide breakdown in isolated human hepatocytes. Furthermore, serendipitly we found that PIP2-PLC activity was increased in liver membranes from obese patients with type II diabetes when compared to obese and lean controls. We conclude that in human liver, insulin and IGFs are not members of the family of hormones generating inositol trisphosphate (IP3) as a second messenger. Furthermore, the increased PIP2-PLC in diabetic liver may result in: (a) increased intracellular concentrations of IP3 and thus increased Ca2+, which has been postulated to induce insulin resistance; and (b) increased diacylglycerol and thus increased protein kinase C which phosphorylates the insulin receptor at serine residues inactivating the insulin receptor kinase. While the mechanism of increased PIP2-PLC activity in diabetes is unknown, it may initiate a cascade of events that result in insulin resistance.

Topics: Calcium; Cell Membrane; Cytosol; Diabetes Mellitus, Type 2; Epinephrine; Guanine Nucleotides; Hydrogen-Ion Concentration; Insulin; Insulin-Like Growth Factor I; Insulin-Like Growth Factor II; Liver; Obesity; Phosphatidylinositol 4,5-Diphosphate; Phosphatidylinositols; Somatomedins; Time Factors; Type C Phospholipases; Vasopressins

Topics: Aldosterone; Blood Proteins; Edema; Edema, Cardiac; Extracellular Space; Glomerular Filtration Rate; Humans; Liver Cirrhosis; Natriuretic Agents; Nephritis; Obesity; Proteins; Vasopressins; Water-Electrolyte Balance

Topics: Adrenocorticotropic Hormone; Adult; Aldosterone; Humans; Hypertension; Obesity; Renin; Secretory Rate; Vasopressins

Topics: Animals; Aurothioglucose; Dietary Fats; Fatty Acids; Female; Liver; Mice; Mice, Obese; Obesity; Vasopressins

Topics: Adolescent; Adrenocorticotropic Hormone; Adult; Female; Humans; Hypothalamo-Hypophyseal System; Insulin; Male; Middle Aged; Obesity; Pituitary-Adrenal System; Vasopressins

Topics: Animals; Arginine Vasopressin; Hypothalamus; Hypothalamus, Anterior; Male; Obesity; Oxytocin; Pituitary Gland; Rats; Vasopressins

Topics: Angiotensin II; Animals; Diabetes Mellitus; Epinephrine; Fatty Acids, Nonesterified; Glucagon; Glucose; Glycerides; Hormones; Insulin; Liver; Liver Glycogen; Nucleotides, Cyclic; Obesity; Oxytocin; Parathyroid Hormone; Protein Kinases; Starvation; Stress, Physiological; Vasopressins

Topics: Adult; Humans; Hydrocortisone; Insulin; Levodopa; Lypressin; Obesity; Pituitary-Adrenal System; Vasopressins

1. Fatty acid synthesis, measured in the perfused liver of genetically obese (ob/ob) mice with 3H2O or [14C]actate, did not show the inhibition by [8-arginine]vasopressin (antidiuretic hormone) that is observed in livers from normal mice. 2. Hepatic glycogen breakdown in obese mice was stimuulated by vasopressin, but not as extensively as in lean mice. 3. If obese mice received a restricted amount of food, then fatty acid synthesis still did not respond to vasopressin, but glycogen breakdown was fully stimulated. 4. Cholesterol synthesis was not inhibited by vasopressin in livers from obese mice. 5. Vasopressin inhibited fatty acid synthesis in intact lean mice, but not in obese animals. 6. These results suggest that genetic obesity could be due to an inborn error within the mechanisms (other than adenylate cyclase) which mediate responses to extracellular effectors.

Topics: Animals; Cholesterol; Diet; Fatty Acids; Female; Glucose; Liver; Liver Glycogen; Mice; Mice, Obese; Obesity; Vasopressins

Topics: Adipose Tissue; Amino Acids; Animals; Epinephrine; Fatty Acids, Nonesterified; Female; Growth Hormone; Humans; Hypopituitarism; Neurophysins; Obesity; Oxytocin; Species Specificity; Vasopressins

The renal tubular responsiveness to antidiuretic hormone was assessed in seven obese patients during starvation and feeding by an overnight dehydration test followed by exogenous vasopressin. All seven subjects showed a mean reduction of one-third in their maximum urinary osmolality on day 4 of starvation. Thes- data show that the renal tubule is partially insensitive to antidiuretic hormone at a time when it is also insensitive to mineralocorticoids.?Author

Topics: Adult; Body Weight; Dehydration; Diet; Fasting; Humans; Kidney Tubules; Middle Aged; Mineralocorticoids; Nutritional Physiological Phenomena; Obesity; Osmolar Concentration; Time Factors; Urination; Urine; Vasopressins

Topics: Adrenocorticotropic Hormone; Arginine; Diethylstilbestrol; Dihydroxyphenylalanine; Endotoxins; Female; Glucagon; Glucocorticoids; Glucose; Gonadal Steroid Hormones; Growth Hormone; Humans; Hypoglycemia; Hypothyroidism; Insulin; Male; Obesity; Physical Exertion; Pituitary Function Tests; Pseudomonas; Puberty; Sleep; Vasopressins

Topics: Adult; Aldosterone; Blood Pressure; Blood Vessels; Catecholamines; Female; Humans; Hydrocortisone; Hypertension; Male; Norepinephrine; Obesity; Pulse; Vasopressins

Topics: Adrenal Cortex; Adrenal Glands; Adult; Diencephalon; Female; Humans; Lypressin; Male; Obesity; Pituitary Gland; Vasopressins

Topics: Adolescent; Carbohydrate Metabolism, Inborn Errors; Chorionic Gonadotropin; Deficiency Diseases; Gonadotropin-Releasing Hormone; Growth Hormone; Humans; Hydroxysteroids; Hypogonadism; Intellectual Disability; Luteinizing Hormone; Male; Obesity; Pituitary Diseases; Syndrome; Testosterone; Thyrotropin; Vasopressins

Topics: Adolescent; Aminosalicylic Acids; Blood Glucose; Body Height; Calcinosis; Child; Child, Preschool; Diabetes Insipidus; Female; Growth Hormone; Hemiplegia; Humans; Hypopituitarism; Isoniazid; Obesity; Prednisone; Pyrazinamide; Streptomycin; Tuberculosis, Meningeal; Vasopressins

Topics: Adolescent; Albumins; Body Water; Chronic Disease; Circadian Rhythm; Dehydration; Diabetes Insipidus; Glucose Tolerance Test; Humans; Hypernatremia; Hypogonadism; Hypothalamus; Intellectual Disability; Kidney Diseases; Male; Obesity; Polyuria; Renin; Sodium; Thirst; Vasopressins

Topics: 11-Hydroxycorticosteroids; 17-Hydroxycorticosteroids; Adolescent; Adrenal Glands; Adrenal Insufficiency; Blood Glucose; Child; Child, Preschool; Dwarfism; Evaluation Studies as Topic; Female; Humans; Hypoglycemia; Hypopituitarism; Hypothalamus; Insulin; Lysine; Male; Metyrapone; Obesity; Pituitary Gland; Pituitary-Adrenal Function Tests; Time Factors; Vasopressins

Topics: Adrenocorticotropic Hormone; Estrogens; Female; Glucocorticoids; Humans; Hypogonadism; Hypopituitarism; Hypothalamo-Hypophyseal System; Injections, Intramuscular; Injections, Intravenous; Lysine; Male; Menstruation Disturbances; Obesity; Pituitary Function Tests; Prednisolone; Turner Syndrome; Vasopressins

Topics: Brain Neoplasms; Child; Chlorpropamide; Craniopharyngioma; Cysts; Dehydration; Diabetes Insipidus; Drinking Behavior; Female; Humans; Kidney Concentrating Ability; Male; Obesity; Osmolar Concentration; Sodium; Thirst; Vasopressins; Water-Electrolyte Balance

Topics: Adult; Female; Humans; Middle Aged; Obesity; Vasopressins

Topics: Animals; Diuresis; Feeding Behavior; Hypothalamo-Hypophyseal System; Hypothalamus; Kidney Concentrating Ability; Obesity; Proteinuria; Rats; Species Specificity; Vasopressins; Water-Electrolyte Balance

Topics: Adolescent; Adult; Aged; Anesthesia, Inhalation; Blood Urea Nitrogen; Creatinine; Diuresis; Female; Humans; Kidney; Kidney Function Tests; Male; Methoxyflurane; Middle Aged; Obesity; Osmolar Concentration; Postoperative Complications; Sodium; Succinylcholine; Thiopental; Urine; Vasopressins; Water-Electrolyte Balance

Topics: 17-Hydroxycorticosteroids; 17-Ketosteroids; Adolescent; Adult; Carbon Isotopes; Circadian Rhythm; Cushing Syndrome; Diagnosis, Differential; Fasting; Female; Humans; Hydrocortisone; Hypothalamo-Hypophyseal System; Male; Middle Aged; Obesity; Pituitary-Adrenal System; Secretory Rate; Steroids; Vasopressins

Topics: 17-Hydroxycorticosteroids; Adolescent; Adrenal Cortex Hormones; Adrenocorticotropic Hormone; Blood Glucose; Child; Child, Preschool; Female; Growth Disorders; Growth Hormone; Humans; Hypoglycemia; Infant; Insulin; Male; Metyrapone; Obesity; Pituitary Diseases; Pituitary-Adrenal Function Tests; Psychosexual Development; Puberty; Puberty, Precocious; Urine; Vasopressins; Virilism

Topics: Adolescent; Adrenal Glands; Child; Child, Preschool; Fatty Acids, Nonesterified; Female; Humans; Hydrocortisone; Hypothalamo-Hypophyseal System; Lysine; Male; Metyrapone; Obesity; Pituitary Function Tests; Pituitary Gland; Vasopressins

Topics: Bloodletting; Humans; Obesity; Osmolar Concentration; Vasopressins

Topics: Adolescent; Adrenocorticotropic Hormone; Blood Glucose; Body Height; Body Weight; Brain Neoplasms; Child; Craniopharyngioma; Exercise Test; Feeding and Eating Disorders; Female; Glucose Tolerance Test; Gonadotropins; Growth; Growth Hormone; Humans; Hypothalamus; Insulin; Male; Obesity; Pituitary Neoplasms; Postoperative Complications; Radioimmunoassay; Thirst; Thyrotropin; Vasopressins; Vision Disorders

Topics: Biopsy; Body Temperature; Body Weight; Brain Diseases; Calcium; Child; Child, Preschool; Chlorides; Creatine; Dehydration; Diabetes Insipidus; Diagnosis, Differential; Diet; Diuresis; Feeding and Eating Disorders; Female; Humans; Hydrochlorothiazide; Hypothalamus; Infant; Kidney; Male; Mineralocorticoid Receptor Antagonists; Obesity; Osmolar Concentration; Osmosis; Piperidines; Potassium; Sodium; Urography; Vasopressins

Topics: Adult; Chlorothiazide; Diuresis; Female; Humans; Obesity; Vasopressins

Topics: Adult; Aged; Body Weight; Extracellular Space; Female; Humans; Middle Aged; Obesity; Urination; Urine; Vasopressins; Water; Water-Electrolyte Balance

Topics: Adrenocorticotropic Hormone; Cushing Syndrome; Female; Humans; Hydrocortisone; Insulin; Liver Diseases; Metyrapone; Myxedema; Obesity; Pituitary-Adrenal Function Tests; Pregnancy; Vasopressins

Topics: Adult; Diagnosis, Differential; Female; Heart Diseases; Humans; Hyponatremia; Kidney Diseases; Male; Middle Aged; Obesity; Potassium; Potassium Isotopes; Radioisotope Dilution Technique; Sodium; Sodium Isotopes; Vasopressins

Topics: Arginine Vasopressin; Diabetes Insipidus; Diabetes Insipidus, Neurogenic; Humans; Hypertension; Lysine; Obesity; Vasopressins

Topics: Adrenocortical Hyperfunction; Amenorrhea; Anorexia Nervosa; Diabetes Insipidus; Endocrine System Diseases; Female; Goiter; Graves Disease; Humans; Hypopituitarism; Metabolism; Obesity; Psychology; Psychosomatic Medicine; Psychotherapy; Syndrome; Vasopressins; Water-Electrolyte Balance

Topics: Arginine Vasopressin; Blood Chemical Analysis; Edema; Heart Failure; Humans; Obesity; Vasopressins

Topics: Arginine Vasopressin; Humans; Obesity; Plasma; Vasopressins

Topics: Aldosterone; Arginine Vasopressin; Humans; Obesity; Research; Triiodothyronine; Vasopressins; Water-Electrolyte Balance

Topics: Adiposity; Arginine Vasopressin; Humans; Obesity; Osmolar Concentration; Vasopressins

Topics: Anuria; Arginine Vasopressin; Humans; Obesity; Oliguria; Vasopressins