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

There exists a growing body of evidence in women that links androgen excess to increases in cardiovascular disease and reproductive site neoplasia. Ten to fifteen percent of women exhibit clinical signs and symptoms of hyperandrogenism wherein more extensive evaluation is warranted. Women with adult acne, android-type obesity, and alopecia often have been treated for cosmetic reasons without regard to the underlying pathophysiology. Adverse changes in insulin resistance, lipids, and apoproteins favor earlier progression of diabetes for some patients and an unfavorable cardiovascular risk profile for most. Patients with polycystic ovarian syndrome (PCOS) often present to different health providers with different complaints that include excessive facial hair, obesity, hypertension, impaired glucose tolerance, dysfunctional uterine bleeding, or infertility. First-line treatment options, after excluding ovarian or adrenal tumors, include use of non-androgenic OCs until pregnancy is desired. Early identification of patients allows for use of risk-reduction strategies, which may affect clinical outcomes.
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PMID:Androgen excess in women. 882 97

Obesity, altered pattern of gonadal hormone secretion, advanced vaginal opening, irregular cycling, altered sexual behavior and infertility are the effects of the neonatal administration of monosodium glutamate (MSG) to rodents. These are the consequences of lesions located mainly in the hypothalamic region. It is believed that the receptors to N-methyl-D-aspartic acid (NMDA) actively participate in the onset and development of such lesions, on the other hand, they may be altered by neuronal dysfunction as well, seriously compromising the glutamatergic pathways that are involved in the neuroendocrine regulation. To clarify the scope of the lesion induced by MSG and its probable effects on the NMDA receptors, we measured them with a very sensitive ligand for autoradiography, (+)-3-[125I]MK-801. Coronal cuts at the level of the arcuate-median eminence of brains from 4-, 8- and 40-day-old rats treated neonatally with MSG (4 mg/g) or saline (controls) were examined. In the normal hypothalamus, NMDA receptor labelling was higher in the young animals than in the 40-day-old animals, and this was observed in both control and treated rats. NMDA receptor labelling of rats at puberty was very low, and no apparent differences were observed between groups. In contrast, in areas where an increase in NMDA binding sites normally occurs with development, a significant impairment of the normal augmentation of MK-801 binding was revealed. In the hippocampal layers, stratum radiatum and stratum oriens and in the cerebral cortex of 40-day-old rats treated with MSG a lower amount of binding was observed, of about 50% fewer sites compared to the untreated controls at the level of CA3 and in the outer layer of the parietal cortex. These results suggest that at an early stage of the MSG lesion the NMDA receptors located in the hypothalamus and other brain areas are apparently expressed normally, but at puberty the effects of the lesion are revealed in the hippocampus and cerebral cortex by a decrease in the density of binding. Thus, the abnormal neuroendocrine and behavioral responses displayed by the MSG-treated rats may be contributed partially by the alteration of the NMDA receptors in these areas.
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PMID:Decrease of (+)-3-[125I]MK-801 binding to NMDA brain receptors revealed at puberty in rats treated neonatally with monosodium glutamate. 887 89

The high prevalence of obesity and its well documented association with the cardiovascular risk factors diabetes mellitus, dyslipidemia and hypertension represents a major problem for the general health status of industrialized societies. Although numerous studies have shown that genetic factors have a major influence on the regulation of energy homeostasis and the susceptibility to obesity, the genes and predisposing mutations involved are insufficiently understood. Among several known rodent models of obesity due to single gene mutations, mice homozygous for the obese (ob) gene exhibit massive early-onset obesity, hyperphagia, non-insulin-dependent diabetes mellitus, defective thermoregulation and infertility. Recently the ob gene was identified by positional cloning and shown to be mutated in ob/ob mice. Leptin, the product of the ob gene, is a 167-amino acid secreted protein that is synthesized exclusively in adipose tissue. With the exception of ob/ob mice, circulating plasma leptin is elevated in obesity. Administration of recombinant leptin to ob/ob mice reduces fat mass, food intake, hyperglycemia and hyperinsulinemia. The various effects of the hormone are mediated by leptin receptors expressed at high levels in the hypothalamus, but also in several other non-neuronal tissues. A mutation in the leptin receptor gene is responsible for the obese phenotype of db/db mice. Plasma leptin in humans is positively correlated with body fat mass, suggesting that leptin resistance rather than leptin deficiency is a common feature of human obesity. This review briefly summarizes the current status of the rapidly growing evidence that leptin plays an important role in the regulation of body weight and fat deposition.
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PMID:Regulation of energy balance by leptin. 888 45

This study was designed to investigate the effects of weight loss in obese, infertile women with special interest in changes of blood hormones, menstrual function and pregnancy rate. Blood glucose, insulin, C-peptide and different steroid and pituitary hormones during oral glucose loading were determined in a group of 58 obese women with menstrual irregularities. Of the 58 women, 35 took part in a weight-reducing programme lasting 32 +/- 14 weeks (mean +/- SD) with a weight loss of 10.2 +/- 7.9 kg (therapy group). At the time of first oral glucose tolerance testing, insulin resistance was a feature in 85% of the women in the therapy group, and 22% were hyperandrogenaemic. Weight loss resulted in a significant reduction in blood glucose, insulin, androstenedione, dihydrotestosterone and oestradiol concentrations. The pregnancy rate was 29% in this group and of them, 80% showed an improvement of their menstrual function. Thus, weight reduction is the appropriate treatment for women with obesity-related endocrine derangement, menstrual irregularity and infertility.
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PMID:Effects of weight loss on the hormonal profile in obese, infertile women. 892 Oct 59

Recent data in the mouse demonstrate that leptin, a protein hormone produced by fat cells, is required for fertility. In the absence of leptin the mice become obese, diabetic and infertile. Polycystic ovary syndrome (PCOS), a common cause of infertility in women, is associated with obesity and insulin resistance. Because of the increased frequency of PCOS in obese women we tested the hypothesis that alterations in serum leptin concentrations might be associated with PCOS. Immunoreactive leptin concentrations were measured in 58 women with PCOS and 70 regularly menstruating (control) women. As has previously been shown there was a positive correlation between leptin levels and body mass index (BMI). Although the leptin levels in the majority of women with PCOS fell within the control range, 29% of PCOS women had leptin levels above the 99% prediction interval for their BMI and none had low leptin levels. There were also positive correlations of leptin levels with free testosterone and insulin sensitivity in control women. In women with PCOS, 13% and 9.5% exhibited higher than expected leptin concentrations with respect to free testosterone and insulin sensitivity, respectively. Insulin resistant PCOS women had higher leptin levels than controls. The data demonstrate that a substantial proportion of women with PCOS have leptin levels that are higher than expected for their BMI, free testosterone and insulin sensitivity. These results suggest that abnormalities in leptin signaling to the reproductive system may be involved in certain cases of PCOS.
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PMID:Serum immunoreactive leptin concentrations in women with polycystic ovary syndrome. 892 78

Obese Zucker female rats are infertile. The present study was designed to assess estrous cyclicity in adult, ovary-intact, lean and obese Zucker rats and to compare reproductive behaviors induced by exogenous steroid hormones in ovariectomized (ovx) lean and obese Zucker rats. The majority (90%) of obese rats had incomplete cycles in comparison with the normal, 4-day cycles displayed by lean Zucker rats. After ovariectomy, all rats were treated with estradiol benzoate (EB, 15-100 micrograms/kg) or EB plus progesterone (P, 2-20 mg/kg), and tested for sexual receptivity and proceptivity (PRO). At the highest EB dose, obese Zucker females displayed lordosis less frequently than lean rats (lordosis quotient, LQ, 8 +/- 6% vs. 32 +/- 13%, respectively). At the lowest doses of EB plus P, lean females were extremely receptive and proceptive (LQ = 93 +/- 4%, PRO = 6.2 +/- 2 bouts/min). Zucker obese females, in contrast, were only slightly receptive (LQ = 26 +/- 11%) and showed less PRO than lean rats (PRO = 2.4 +/- 0.6 bouts/min). Increasing the dose of either EB or P, administered in combination with the lowest dose of the other hormone, produced receptivity and PRO in obese Zucker females that were comparable with those observed in lean rats. Serum estradiol and P levels in ovx obese rats were either equivalent to or higher than those in the ovx lean rats when both were given the same doses of hormones. These data suggest that considerably higher doses and serum concentrations of EB and/or P are required to elicit robust lordosis and PRO in ovx obese Zucker than in lean rats. This behavioral hyporesponsiveness to sex steroid hormones may contribute to infertility in the obese Zucker female rat.
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PMID:Abnormal estrous cyclicity and behavioral hyporesponsiveness to ovarian hormones in genetically obese Zucker female rats. 897 97

We present the case of an 11 year-old boy, who asked for medical attention due to obesity and assumed underdeveloped external genitalia. He did not have genital anomalies, penile length was 5.3 cm, testicular volume 2 ml and pubic hair Tanner stage 1. His bone age was normal for chronological age. Endocrinological study showed normal results for his age. Karyotype revealed a 46 XX pattern. MRI of external genitalia showed bilateral scrotal testes which were normal in diameter for his age. The check of his historical growth chart and follow-up revealed normal growth with spontaneous pubertal development. However, hormonal studies showed progressive increase of FSH levels, indicative of failure of germinal epithelium. The presence of Y sequences, including SRY gene, was demonstrated by PCR. Our observation is in agreement with the view that 46 XX male subjects diagnosed at peripubertal age with the SRY gene in the genome have a good prognosis regarding growth and development, but the principal problem of these patients is infertility.
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PMID:Development in a 46 XX boy with positive SRY gene. 900 79

Cpefat mice carry a mutation in the carboxypeptidase E/H gene which encodes an exopeptidase that removes C-terminal basic residues from endoproteolytically cleaved hormone intermediates. These mice have endocrine disorders including obesity, infertility, and hyperproinsulinemia-diabetes syndrome, but the etiology remains an enigma. Because studies have identified membrane carboxypeptidase E as a sorting receptor for targeting prohormones to the regulated secretory pathway for processing and secretion, the intracellular routing and secretion of pro-opiomelanocortin/adrenocorticotropin and growth hormone from anterior pituitary cells were investigated in Cpefat mice. In Cpefat mice, pro-opiomelanocortin was accumulated 24-fold above normal animals in the pituitary and it was poorly processed to adrenocorticotropin. Furthermore, pro-opiomelanocortin was secreted constitutively at high levels, showing no response to stimulation by corticotropin-releasing hormone. Similarly, growth hormone release was constitutive and did not respond to high K+ stimulation. Both pro-opiomelanocortin and growth hormone levels were elevated in the circulation of Cpefat mice versus normal mice. These data provide evidence that the lack of carboxypeptidase E, the sorting receptor, results in the intracellular misrouting and secretion of pro-opiomelanocortin and growth hormone via the constitutive pathway in the pituitary of Cpefat mice.
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PMID:Intracellular misrouting and abnormal secretion of adrenocorticotropin and growth hormone in cpefat mice associated with a carboxypeptidase E mutation. 914 34

Mutations in the obese gene (OB) or in the gene encoding the OB receptor(OB-R) result in obesity, infertility and diabetes in a variety of mouse phenotypes. The demonstration that OB protein (also known as leptin) can normalize body weight in ob/ob mice has generated enormous interest. Most human obesity does not appear to result from a mutant form of leptin: rather, serum leptin concentrations are increased and there is an apparent inability to transport it to the central nervous system (CNS). Injection of leptin into the CNS of overfed rodents resistant to peripheral administration was found to induce biological activity. Consequently, for the leptin to act as a weight-lowering hormone in human obesity, it appears that appropriate concentrations must be present in the CNS. This places a premium on understanding the structure of the hormone in order to design more potent and selective agonists. Here we report the crystal structure at 2.4A resolution of a human mutant OB protein (leptin-E100) that has comparable biological activity to wild type but which crystallizes more readily. The structure reveals a four-helix bundle similar to that of the long-chain helical cytokine family.
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PMID:Crystal structure of the obese protein leptin-E100. 914 95

Obesity is associated with the development of some of the most prevalent diseases of modern society. The greatest risk is for diabetes mellitus where a body mass index above 35 kg/m2 increases the risk by 93-fold in women and by 42-fold in men. The risk of coronary heart disease is increased 86% by a 20% rise in weight in males, whereas in obese women the risk is increased 3.6-fold. Elevation of blood pressure, hyperlipidaemia and altered haemostatic factors are implicated in this high risk from coronary heart disease. Gallbladder disease is increased 2.7-fold with an enhanced cancer risk especially for colorectal cancer in males and cancer of the endometrium and biliary passages in females. Endocrine changes are associated with metabolic diseases and infertility, and respiratory problems result in sleep apnoea, hypoventilation, arrhythmias and eventual cardiac failure. Obesity is not a social stigma but an actual disease with a major genetic component to its aetiology and a financial cost estimated at $69 billion for the USA alone.
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PMID:Obesity as a disease. 924 38


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