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Query: UMLS:C0028754 (obesity)
 124,988 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The metabolic syndrome is discussed in terms of insulin resistance linked to an increased regulation of metabolism by cortisol and fatty acids. This change in hormonal balance is associated with diabetes, android (visceral) obesity, hypertension, hypertriglyceridemia, hyperapobetalipoproteinemia and low concentrations of HDL; a cluster of risk-factors that predisposes to the development of premature atherosclerosis. It is proposed that the metabolic syndrome is accompanied by a derangement in the hypothalamic-pituitary-adrenal-axis such that the effects of cortisol are exaggerated relative to those of CRF. Excessive action of fatty acids and cortisol causes insulin resistance and increase the hepatic secretion of glucose and VLDL. Furthermore, cortisol can decrease the uptake of LDL by the liver. Cortisol in the presence of relatively high insulin concentrations can promote the deposition of energy and lead to obesity. Chronic treatment of rats with D-fenfluramine has been shown to decrease the release of cortisol and fatty acids in response to stress, and to improve insulin sensitivity. The effects of D-fenfluramine were also tested in male JCR:LA corpulent rats which are prone to develop atherosclerosis and myocardial lesions. D-fenfluramine improved insulin sensitivity, decreased the hypertriglyceridemia, and prevented the development of necrotic myocardial lesions caused by ischemia. The data presented demonstrates a link between excessive action of cortisol and fatty acids in predisposing to insulin resistance and the pathologies that are associated with the metabolic syndrome.
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PMID:Role of glucocorticoids and fatty acids in the impairment of lipid metabolism observed in the metabolic syndrome. 755 May 41

The relationships of cigarette smoking, age, relative weight, and dietary intake to serum dehydroepiandrosterone (DHEA), dehydroepiandrosterone sulfate (DHEAS), androstenedione, cortisol, 3-alpha-androstanediol, 3-alpha-androstanediol-glucuronide, testosterone, albumin-bound testosterone, free testosterone, dihydrotestosterone (DHT), and sex hormone-binding globulin (SHBG) were examined cross-sectionally in 1241 randomly sampled middle-aged U.S. men. Compared with nonsmokers and independent of relative weight (body mass index) and age, cigarette smokers had increased serum levels of DHEA (18% higher, P = 0.0002), DHEAS (13% higher, P = 0.0007), cortisol (5% higher, P = 0.01), androstenedione (33% higher, P = 0.0001), testosterone (9% higher, P = 0.009), DHT (14% higher, P = 0.004), and SHBG (8% higher, P = 0.004). Androstenedione, total plasma testosterone, albumin-bound testosterone, DHT, and SHBG decreased with increasing relative weight. Age was positively associated with serum SHBG and negatively associated with albumin-bound testosterone, DHEA, and DHEAS. An association was found between alcohol intake and DHEA (r = 0.15; P = 0.0001), cortisol (r = 0.10; P = 0.0007), and 3-alpha-androstanediol-glucuronide (r = 0.08; P = 0.0004). Cortisol was the only hormone that was associated with carbohydrate intake (r = -0.09; P = 0.002). The only hormones associated with dietary lipids were DHT (for vegetable fat, r = 0.07; P = 0.02), cortisol (for total fat, r = 0.08; P = 0.007), and SHBG (for animal fat, r = -0.06; P = 0.05). In addition, SHBG was positively associated with dietary (r = 0.07; P = 0.008) and crude (r = 0.08; P = 0.007) fiber. These data suggest that serum adrenal steroid and sex hormone concentrations in middle-aged men are more influenced by cigarette smoking, age, and obesity than by dietary intake; however, serum adrenal steroids were influenced by alcohol intake.
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PMID:The relation of smoking, age, relative weight, and dietary intake to serum adrenal steroids, sex hormones, and sex hormone-binding globulin in middle-aged men. 796 22

Obesity, the most frequent nutritional problem throughout the rich nations, can have a vast and significant influence on different aspects of endocrinology, in particular on ovulation disfunction, on hyperandrogenemia, on hormone-sensitive carcinomas. Our study proposes to value the response to adrenal cortex to stimulation with adrenocorticotropin (ACTH) hormone in obese patients, with particular attention to the behavior of adrenocortical androgens and their precursor. We recruited 30 female patients so divided: 12 obese, nonhirsute, eumenorrheic patients (group A); 10 normal weight, hirsute patients in situation of secondary amenorrhea (group B); 8 normal weight, nonhirsute, eumenorrheic patients (group C). Cortisol, progesterone, 17 OH progesterone, dehydroepiandrosterone sulfate, androstenedione, testosterone were measured at 60, 120, 180, 240, 300 min during continual infusion i.v., for 5 h, of ACTH 1-17 at 100 mcg dose, in physiological sodium chloride solution. All the women with monthly menstruation were studied between the IV and VIII day of their cycle. In the patients with secondary amenorrhea the value of basic progesterone was used to completely exclude an eventual luteal phase and the relationship LH/FSH was so as to logically exclude a diagnosis of polycystic ovary. This exclusion was also confirmed from the report of the ultrasonography. The basic concentration of hormone dosage is not significantly different between the patients of the three groups, except for T. This hormone is different because it is found to be significantly (p < 0.01) increase in the hirsute patients, in respect of the patients in group A and group C. Also P and 17OHP have been found to be higher, if only in insignificant measure, in hirsute patients.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Probable role of obesity on the adrenal response to acute stimulation with adrenocorticotrophic hormone in eumenorrheic and hirsute, non-eumenorrheic women]. 823 17

Smoking exerts influences on the secretion of several hormones which are abnormal in obesity. Previous studies have mainly been performed in non-obese men, and data from non-obese and obese women are scarce. The aim of the present study was therefore to identify the effect of smoking on hormone secretions in obese and lean female smokers. The study was performed in 10 obese and 8 lean, premenopausal, healthy smokers. All subjects were tested once under experimental and once under control conditions (not smoking) in randomized order. The women smoked two non-filtered cigarettes during 4 minutes each. Blood pressure and heart rate were measured 30 minutes before smoking, at the start of smoking (time 0) and then after 5, 10, 20, 30, 45 and 60 minutes. Blood samples were taken for determination of serum concentrations of adrenocorticotropic hormone (ACTH), cortisol, prolactin (PRL), growth hormone (GH) and thyroid stimulating hormone (TSH) at the same time points except at 5 minutes. Heart rate rose in both groups during smoking. Systolic and diastolic blood pressure was increased only in the obese subjects. Cortisol and ACTH increased in both groups, while TSH, PRL and GH were unchanged in both groups. We conclude that lean and obese smoking women seem to respond rather similarly to smoking in the hemodynamic and endocrine variables measured in this report with the possible exception of blood pressure where the obese women tended to show more pronounced increases.
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PMID:Influence of smoking on hormone secretion in obese and lean female smokers. 882 56

The case of a woman of 27 affected by the Prader-Willi syndrome who underwent general anaesthesia for dental surgery is reported. The patient presented severe mental retardation, small stature, moderate muscular hypotonia, hyperphagia, obesity, and diabetes mellitus. Premedication consisted of diazepam and atropine; anaesthesia was induced with propofol and maintained with propofol, fentanyl and N2O; muscle paralysis was obtained with atracurium. A small glottis was observed at laryngoscopy so that a 6 mm cuffed tube was inserted. Surgery lasted 75 minutes; the patient recovered promptly a few minutes following the end of propofol infusion; no postoperative complication was recorded. As hypoglycemia can occur during and after surgery in the Prader-Willi syndrome, plasma samples for glucose, NEFA, insulin, cortisol, and growth hormone (GH) were collected prior to the induction of anaesthesia (A), 20 minutes after starting surgery (B), at the end of surgery (C), and 3 hours later (D). In spite of the infusion of glucose, hyperglycemia was observed just in C and D samples (A:77; B:88; C:245; D:279 mg/dl). Stable NEFA values, within the normal range, were observed (A:77; B:88; C:245; D:279 mg/dl) suggesting poor or absent lipolysis. Insulin decreased progressively during surgery (A:10.5; B:8.8; C:5.4; D:7.0 mU/L). Cortisol peaked in B (A:9.5; B:20.9; C:13.4; D:4.8 micrograms/dl), suggesting normal hypothalamic reactivity to the surgical stimulus. Finally very low GH levels were observed (A:0.04; B:0.07; C:0.06; D:0.09 ng/ml) suggesting GH deficiency, which had possibly affected the size of patient's glottis. Our data support the hypothesis that hypoglycemia in the Prader-Willi syndrome originates from inadequate lipolysis during starvation.
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PMID:[General anesthesia in Prader-Willi syndrome]. 910 80

Little is known about the effects of intentional weight loss on the function of the hypothalamic-pituitary-adrenal (HPA) axis of obese individuals. We studied the HPA axis of 34 healthy obese women (body mass index, 40.2 +/- 7.9 kg/m2) before and after a 21.0 +/- 7.9-kg weight loss induced by a 26-week weight loss program that included 12 weeks of a 3350 kJ/day (800 Cal/day) liquid formula diet, 6 weeks of gradual refeeding, and 6 weeks of caloric stabilization at 5020-6280 kJ/day (1200-1500 Cal/day). Obese subjects were evaluated twice: before caloric restriction and during the last 3 weeks of caloric stabilization with a 3-h evening 1 microg/kg ovine CRH (oCRH) stimulation test. CRH-stimulated ACTH and cortisol values were compared to those of a control group of 12 normal weight women. Before caloric restriction, both ACTH and cortisol responses to oCRH were similar in obese women and normal weight controls. Weight loss did not significantly alter the ACTH response to oCRH; however, the total plasma cortisol response to oCRH decreased significantly with weight loss (area under the curve, 96,320 +/- 21,040 nmol/L x min before weight loss; 82,450 +/- 22,460 nmol/L x min after weight loss; P < 0.001). Cortisol-binding globulin also decreased significantly after weight loss (2,270 +/- 1,050 nmol/L) compared either to values obtained before weight loss (3,590 +/- 1,360 nmol/L; P < 0.001) or to those of normal weight controls (3,910 +/- 1,400 nmol/L; P < 0.001). Assay for plasma free cortisol, either before or 180 min after oCRH treatment, showed no significant changes in cortisol responses resulting from weight loss. As plasma free cortisol was not altered by weight reduction, the decrease in the total cortisol response to oCRH after weight loss appears to be secondary to significant decreases in cortisol-binding globulin. We conclude that when obese women lose large amounts of weight with a 3350 kJ/day, very low energy diet, such weight reduction does not significantly affect the HPA axis.
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PMID:Differences in corticotropin-releasing hormone-stimulated adrenocorticotropin and cortisol before and after weight loss. 917 99

In obesity, urinary cortisol excretion is enhanced but plasma cortisol levels are not elevated, suggesting that metabolic clearance of cortisol is increased. Cortisol is metabolised in liver and fat by A-ring reductases but also regenerated from inactive cortisone in liver, fat, and skeletal muscle by 11 beta-reductase. These enzymes are regulated by estrogen. This study addressed whether there are differences in cortisol metabolism in obesity, and whether these differences are estrogen dependent. 31 men and 37 post-menopausal women (9 on estrogen replacement therapy) aged 47-53 y supplied 24 h urine for gas chromatography/mass spectrometry. Total cortisol metabolite excretion was higher in men than women, but weakly related to indices of obesity. By contrast, metabolism of cortisol favoured 5 alpha-rather than 5 beta-reduction in obese men and obese women, and favoured cortisol rather than cortisone in obese men. In women compared with men ratios of 5 alpha-/5 beta-reduced and cortisol/cortisone metabolites were also higher but these variables were not affected by estrogen replacement therapy. We conclude that in obesity, inactivation of cortisol by 5 alpha-reductase is enhanced but this is offset by impaired metabolism of cortisol by 5 beta-reductase in women and enhanced conversion of cortisone to cortisol by 11 beta-reductase in men. These observations suggest that cortisol clearance is altered in obesity, and this may account for activation of the hypothalamic-pituitary-adrenal axis. Moreover, these data predict that obese subjects will have higher concentrations of cortisol in key target tissues including liver and visceral fat. This may contribute to the adverse metabolic consequences of obesity.
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PMID:Obesity and gender influence cortisol secretion and metabolism in man. 1037 45

Abdominal obesity has been suggested to be associated with perturbations of the regulation of the hypothalamic-pituitary-adrenal (HPA) axis. In a population of 51-yr-old men (n = 284) salivary cortisol concentrations were determined on repeated (n = 7) occasions over a random working day, and perceived stress was reported in parallel. Cortisol values were then related to reported stress (stress-related cortisol). A standardized lunch was used as a physiological challenge. A low dose (0.5 mg) dexamethasone suppression test was also performed as well as determinations of testosterone and insulin-like growth factor I (IGF-I). Body mass index [weight (kilograms)/height (meters)2]; waist/hip circumference ratio (WHR); sagittal trunk recumbent diameter (D); fasting insulin; blood glucose; triglycerides; and total, low density (LDL), and high density (HDL) lipoprotein cholesterol were also determined. Cortisol concentrations were highest in the morning, and lunch was followed by a peak (P = 0.044). Two types of diurnal cortisol curves were identified, one characterized by a high variability with high morning values, and another with low variability and low morning values. Both correlated strongly with suppression of salivary cortisol by dexamethasone (P < 0.001). Stress-related cortisol secretion was associated with D (P = 0.051), low IGF-I (P = 0.006), and diastolic blood pressure (P = 0.078). When the type of diurnal cortisol curve was taken into consideration by statistical weighting, stress-related cortisol secretion in subjects with high variability showed associations with testosterone (P < 0.001), D, total and LDL cholesterol, diastolic blood pressure (P < 0.001), fasting insulin (P = 0.039), and glucose (P = 0.030) as well as, negatively, triglycerides (P < 0.001). When weighted for a low variability of diurnal cortisol secretion, stress-related cortisol secretion showed strong negative relationships with IGF-I, testosterone, and HDL. Furthermore, strong, consistent relationships (all P < 0.001) were found with obesity factors (body mass index, WHR, and D), and with metabolic (insulin, glucose, triglycerides, and total and LDL cholesterol) as well as hemodynamic variables (systolic and diastolic blood pressure and heart rate). These results clearly show interactions between diurnal cortisol secretion related to perceived stress and anthropometric, endocrine, metabolic, and hemodynamic variables. This seems to occur with apparently normal regulation of the HPA axis (high morning peaks and variability as well as dexamethasone suppression of cortisol), where other endocrine variables are not affected. With a low diurnal cortisol variation and blunted dexamethasone suppression, indicating abnormal regulation of the HPA axis, perceived stress-dependent cortisol values were strongly related to perturbations of other endocrine axes as well as abdominal obesity with metabolic and hemodynamic abnormalities. Perturbations of the regulations of the HPA axis such as those described in combination with low dexamethasone suppressibility are known to follow long term overactivation of the axis by factors such as environmental stress.
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PMID:Stress-related cortisol secretion in men: relationships with abdominal obesity and endocrine, metabolic and hemodynamic abnormalities. 962 6

Plasminogen activator inhibitor 1 (PAI-1) is likely to play a role in vascular disease, primarily in subjects with android obesity. It has been demonstrated that PAI-1 is overexpressed in adipose tissue from obese subjects and that visceral adipose tissue produced more PAI-1 than subcutaneous fat. In the present study, the effect of insulin and glucocorticoids, which are key mediators of adipose tissue metabolism, was examined in relation to PAI-1 synthesis by human adipose tissue explants (HAT), collagenase isolated human adipocytes (IHA), cultured human stromal cells (cSC), and differentiated adipocytes from the murine clonal cell line 3T3-F442A. A significant increase in PAI-1 antigen release (1.5-fold) from HAT was detectable after 16 h of treatment with insulin concentrations of at least 10(-8) mol/l. This was associated with a PAI-1 mRNA increase. Concomitant addition of insulin (10(-8) mol/l) to forskolin (5 x 10(-5) mol/l) reversed the decrease in PAI-1 antigen caused by forskolin alone. No effect on PAI-1 antigen was observed when insulin was incubated with IHA or cSC. 3T3 F442A cells were sensitive to insulin with a four- and twofold increase in PAI-1 antigen and mRNA levels, respectively, after 16 h of stimulation with 10(-8) mol/l. Dexamethasone (DXM) significantly enhanced PAI-1 antigen and mRNA expression by HAT (1.5- and 2.5-fold increase, respectively) at concentrations of at least 10(-8) mol/l. A higher stimulation was observed with IHA (sevenfold increase) and with the differentiated 3T3 F442 cell line. Cortisol was found to be less potent than DXM. No effect was observed when glucocorticoids were incubated with cSC. Coincubation of HAT with insulin (10(-7) mol/l) and DXM (10(-7) mol/l) led to an additive effect on PAI-1 synthesis. These results support the hypothesis that PAI-1 expression in human adipose tissue is controlled by insulin and glucocorticoids and may help to explain the increase in plasma PAI-1 levels observed in patients with android obesity.
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PMID:Glucocorticoids and insulin promote plasminogen activator inhibitor 1 production by human adipose tissue. 1010 8

Insulin resistance is followed by several prevalent diseases. The most common condition with insulin resistance is obesity, particularly when localized to abdominal, visceral regions. A summary of recent reviews on the pathogenesis of systemic insulin resistance indicates that major factors are decreased insulin effects on muscular glycogen synthase or preceding steps in the insulin signalling cascade, on endogenous glucose production and on circulating free fatty acids (FFA) from adipose tissue lipolysis. Contributions of morphologic changes in muscle and other factors are considered more uncertain. Newly developed methodology has made it possible to determine more precisely the neuroendocrine abnormalities in abdominal obesity including increased cortisol and adrenal androgen secretions. This is probably due to a hyperactivity of the hypothalamic-pituitary-adrenal (HPA) axis, amplified by inefficient feedback inhibition by central glucocorticoid receptors, associated with molecular genetic defects. Secondly, secretion of gender-specific sex steroid hormones becomes inhibited and the sympathetic nervous system activated. At this stage the HPA axis shows signs of a 'burned-out' condition, and cortisol secretion is no longer elevated. Cortisol counteracts the insulin activation of glycogen synthase in muscle, the insulin inhibition of hepatic glucose production and the insulin inhibition of lipolysis in adipose tissue, leading to the well-established systemic insulin resistance caused by excess cortisol. This is exaggerated by increased free fatty acid mobilization, particularly with a concomitant elevation of the activity of the sympathetic nervous system. Furthermore, capillarization and fiber composition in muscle are changed. These are the identical perturbations responsible for insulin resistance in recent reviews. The diminished sex steroid secretion in abdominal obesity has the same consequences. It is thus clear that insulin resistance may be induced by neuroendocrine abnormalities, such as those seen in abdominal obesity. These endocrine perturbations also direct excess fat to visceral fat depots via mechanisms that are largely known, indicating why abdominal obesity is commonly associated with insulin resistance. This possible background to the most prevalent condition of insulin resistance has been revealed by development of methodology that allows sufficiently sensitive measurements of HPA axis activity. These findings demonstrate the power of neuroendocrine regulations for somatic health.
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PMID:Neuroendocrine perturbations as a cause of insulin resistance. 1063 68


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