Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0028754 (obesity)
 124,988 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The symptoms of severe early-onset obesity, adrenal insufficiency, and red hair define the proopiomelanocortin (POMC) deficiency syndrome as described so far in two children with complete loss-of-function mutations of the human POMC gene. In POMC deficiency, obesity reflects the lack of POMC-derived peptides as ligands at the melanocortin (MC) MC4 and MC3 receptors, which are expressed in the hypothalamic leptin-melanocortin pathway of body weight regulation. Hypocortisolism and alteration of pigmentation are caused by the lack of POMC-derived peptides at the adrenal MC2 receptor and the skin MC1 receptor, respectively. Here we describe three new cases of complete loss-of-function mutations of the POMC gene. Patients were diagnosed based on the clinical trials of red hair, adrenal insufficiency, and early-onset severe obesity. One previously described translation initiation mutation (C3804A) as well as one new nonsense (A6851T) and two new frame-shift mutations (6996del and 7100 + 2G) were found in homozygosity or compound heterozygosity. The heterozygous parents were found to have high normal or mildly elevated body weight, suggesting a dosage effect of the POMC gene product on weight regulation. To compensate for the lack of hypothalamic melanocortin function, we initiated a trial in the two previously published patients with intranasal ACTH4-10, a melanocortin fragment for which an anorexic effect has been described recently. During 3 months with increasing doses of ACTH4-10, no change of body weight or metabolic rate was observed, suggesting that at least in these two POMC-deficient patients ACTH4-10 is without any compensatory effect. In the same two patients, further investigation revealed a mildly elevated TSH. However, a 1-yr treatment with thyroid hormone did not result in a significant reduction of body weight.
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PMID:Obesity due to proopiomelanocortin deficiency: three new cases and treatment trials with thyroid hormone and ACTH4-10. 1455 33

Sleep loss due to voluntary bedtime curtailment has become a hallmark of modern society. Even though sleep deprivation in rodents has been shown to result in death, it was until a few years ago thought that sleep loss results in increased sleepiness and decreased cognitive performance but has little or no adverse effects on human health. We measured sleep and 24-hour hormonal profiles in 11 healthy young males after 6 days of sleep restriction (4-hour bedtime) and after 6 days of sleep recovery (12-hour bedtime). At the end of sleep restriction, we observed reduced amounts of slow wave sleep (SWS) and rapid eye movement (REM) sleep and an alteration in the temporal distribution of these sleep stages, i.e. an increased pressure for REM sleep at the beginning of the sleep period and a decrease in the amount of slow wave activity (SWA) during the first sleep cycle. These later abnormalities are usually observed in depression. In addition, numerous alterations in the 24-hour hormonal profiles were observed in the state of sleep debt. The amount of melatonin secreted was reduced because of a delay in the onset of the nocturnal secretion and a reduction in the value of the acrophase. If the overall 24-hour cortisol profile was preserved, sleep restriction was associated with increased cortisol levels in late afternoon and evening hours and the duration of the quiescent period was reduced. The 24-hour mean TSH levels were reduced and the nocturnal TSH elevation was markedly dampened, most likely as a result of elevated levels of thyroid hormones. The acrophase of the 24-hour leptin profile occurred earlier, the amplitude of the rhythm and the overall mean levels were reduced. The nocturnal elevation of prolactin levels was abrupt but of short duration and the 24-hour mean levels were decreased. A pulse of growth hormone occurred prior to sleep onset, therefore affecting SWA distribution at the beginning of the sleep period. Since these alterations are qualitatively and quantitatively similar to those observed during aging and sometimes during depression, a state of sleep debt, as is experienced by a substantial fragment of the population in modern societies, is likely to increase the severity of depression and widespread age-related chronic conditions such as obesity, diabetes and hypertension.
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PMID:[Impact of sleep debt on physiological rhythms]. 1464 94

Obesity is considered a primary risk factor for cardiovascular disease and related mortality. The current study aimed to investigate the efficacy of minimal invasive gastric banding (GB) surgery for reducing caloric intake in morbid obesity, and to analyze the effects of weight loss on body composition and metabolic and psychosocial outcomes. Twenty-six adult severely obese patients (mean body mass index [BMI], 48.1 kg/m(2); range, 42 to 56) underwent adjustable silicone laparoscopic GB. Nine additional obese patients who declined surgery were treated with metformin (2 g daily) and served as a small additional group (BMI, 50.5 kg/m(2); range, 41 to 68). Presurgery and 17 +/- 2.2 months postoperatively, body composition (fat mass [FM], lean body mass [LBM], body water) and serum parameters (lipids, glucose, thyrotropin-stimulating hormone [TSH]) were determined. Quality of life (QoL) was evaluated by a standardized self-rating questionnaire (Short Form-36 [SF-36]), and supplemented by measures of physical complaints and psychological distress. After GB, weight loss was 21 +/- 14.9 kg (14%, P <.001). It was associated with a decrease in FM by 14 +/- 8.6 kg (18%, P <.001), LBM by 4 +/- 2.7 kg (5%, P <.001), body water by 4 +/- 3.4 L (7%, P <.01), systolic blood pressure by 16 +/- 26.3 mm Hg (10%, P <.05), total cholesterol by 0.69 +/- 1.29 mmol/L (12%, P <.05), and low-density lipoprotein cholesterol (LDL-C) by 0.38 +/- 0.39 mmol/L (10%, P <.05). Highly significant interactions between surgery and time were noted for weight (P <.005), BMI (P <.005), and FM (P <.007, analysis of variance [ANOVA]). Preoperatively, 14 of 26 patients (54%) had high fasting blood sugar levels (type 2 diabetics) and 11 (42%) had impaired glucose tolerance, whereas postoperatively, for baseline glucose levels a trend to decrease was noted. Neither malabsorption nor anemia was observed. QoL improved after GB; in particular, physical functioning and well being increased (P <.01), and somatic complaints (eg, dyspnea and heart complaints, pain in legs and arms) markedly decreased (P =.008). In the metformin group, neither relevant weight loss nor a significant decrease of biochemical values was observed. Minimal invasive GB is a successful therapeutic tool for reducing FM in morbidly obese patients. Weight loss resulted in improved metabolic parameters, suggesting a lowered atherogenic risk.
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PMID:Metabolic and psychosocial effects of minimal invasive gastric banding for morbid obesity. 1466 54

Dyslipidemia and obesity are common in adult patients with hypopituitarism. Possible contributions of age, sex and hormone deficiencies to hypercholesterolemia and obesity in adult hypopituitary patients were analyzed in 1, 272 Japanese cases based on a database of a national survey on adult hypopituitarism. In patients on routine hormone replacement therapy, 30.5% of male and 40.7% of female subjects were considered hypercholesterolemic. In univariate analysis, hypercholesterolemia was more prevalent in female, aged, untreated Gn-deficient and TSH-deficient groups. In multivariate analysis, sex of female, age older than 40 yr and TSH deficiency were the independent contributing factors to hypercholesterolemia. Obesity (body mass index (BMI) > or = 25 kg/m2) was more prevalent in male, TSH-deficient and ADH-deficient groups. Severe obesity (BMI > or = 30) was observed in high prevalence in the youngest group. These findings suggest that hypercholesterolemia and obesity were prevalent in different age and gender groups in Japanese adult patients with hypopituitarism. Insufficient replacement of thyroid hormone and possibly gonadotropin deficiency might contribute to hypercholesterolemia. In contrast, hypothalamic dysfunction as well as hormone deficiencies might play roles in obesity in these patients.
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PMID:Hypercholesterolemia and obesity in adult patients with hypopituitarism: a report of a nation-wide survey in Japan. 1470 49

We report a 45-year-old woman with Cushing's syndrome showing reversible pituitary dysfunction. Left adrenal tumor was incidentally discovered by a screening examination of abdominal computed tomography. Although this patient lacked typical Cushingoid features except hypertension and leg edema, endocrine examinations revealed moderate suppression of plasma ACTH (~6.3 pg/ml) with relatively high levels of serum cortisol (~22.9 microg/dl) without normal circadian rhythm. Plasma ACTH failed to respond to either CRH or metyrapone, and dexamethasone failed to suppress her daily steroid production. Surgical removal of left adrenocortical adenoma and 6-month replacement of hydrocortisone have ameliorated both ACTH and cortisol responses to CRH loading test. Postoperative responses of TSH and GH to TRH and GRH, respectively, were two fold higher than the preoperative levels. In contrast, basal and TRH-induced levels of serum PRL were decreased after surgery although both the basal and stimulated PRL levels were markedly high before surgery. In addition, gonadotropin response to GnRH examined in the same ovarian cycle was decreased in accordance with an increase in serum estradiol and progesterone levels after surgery. Improvement of hypercortisolemia even in a moderate case of Cushing's syndrome not only ameliorates hypertension, obesity and glucose intolerance, but also restores the accompanying dysfunctions of anterior pituitary, suggesting the clinical importance of early discovery and treatment of functioning adrenocortical incidentalomas.
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PMID:Reversible pituitary dysfunction in a patient with Cushing's syndrome discovered as adrenal incidentaloma. 1511 71

Total body weight is usually employed to calculate the amount of l-T(4) to be administered in patients with thyroid diseases. The aim of this study was to evaluate the effect of body composition on l-T(4) requirements. Body composition was assessed by dual energy x-ray absorptiometry in 75 patients on TSH-suppressive l-T(4) therapy after conventional thyroid ablation for differentiated cancer. The mean daily dose of l-T(4) was lower in normal-weight (127.5 +/- 21.3 mug/d) vs. overweight (139.4 +/- 24.5) and obese (151.3 +/- 29.1) subjects. There was a much stronger association between the l-T(4) dosage and lean body mass (P < 0.001, r = 0.667) compared with fat mass (P = 0.023, r = 0.26). Measurement of regional tissue composition showed peripheral lean mass as the best correlate with the dose of l-T(4) (r = 0.679, P < 0.001) whereas no correlation was observed with peripheral fat mass. In conclusion, individual l-T(4) requirements are dependent on lean body mass. Age- and gender-related differences in l-T(4) needs reflect different proportions of lean mass over the total body weight. An estimate of lean mass may be helpful to shorten the time required to attain a stable dose of l-T(4), particularly in subjects with high body mass index values that may be due either to increased muscular mass or to obesity.
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PMID:Lean body mass is a major determinant of levothyroxine dosage in the treatment of thyroid diseases. 1548 74

By screening 204 diabetes patients, a male with age 38 was found to have increased C-peptide levels in plasma (over 6 ng/ml) and urine (430 microg/day), both of which were the highest among the screened subjects. He developed type 2 diabetes at age 31, without history of obesity (weight was 52 kg and height 170 cm). He had bilateral testicular atrophy. Fasting plasma glucose level was 160 mg/dl and HbA1c was 8% at age 38. There was hypertriglycemia (290-662 mg/dl). There were no abnormal peaks of IRI or CPR in the serum fractionated by gel filtration (Biogel P 30). Molar ratio of p-CPR/s-IRI was 10.8. Islet cell antibody, anti-insulin binding antibody and anti-insulin receptor antibody were negative. LSH and FSH were both elevated, and free testosterone was decreased. TSH and Leptin levels were elevated. Other laboratory data were within normal range. CT scan revealed fatty liver and horse-shoe kidney. These clinical pictures do not match the criteria to known syndromes associated with diabetes. Although the single case report is insufficient to discuss the C-peptide mechanism of action, this case may give us a hint to understand an aspect of the pathophysiology of C-peptide's bioactivity dysfunction.
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PMID:A case of type 2 diabetes with high levels of plasma and urinary C-peptide. 1556 62

The hypothalamus has long been recognized as a major site in the central nervous system (CNS) where a spectrum of internal and external environmental information is integrated for energy homeostasis. The isolation and sequencing of leptin in the mid 90 s, together with the demonstration of leptin administration's ability to correct the obesity syndrome in leptin-deficient ob/ob mice and humans by suppressing food intake and weight gain in laboratory rodents, confirmed the hypothesized existence of a direct humoral signal from adipose tissue to the hypothalamus, thus integrating the energy-related signals. In the 80 s, neuropeptide Y (NPY) was identified as a potent appetite-stimulating neuropeptide produced, released and acting locally within the hypothalamus. This is recognized as a major physiological appetite transducer and central neurochemical substrate receiving, interpreting and processing incoming information on energy status. More recently, ghrelin, produced in the stomach and released into the general circulation, has drawn attention as the other limb of the feedback circuit that stimulates appetite at NPY network level. Prolonged fasting suppresses serum leptin, while suppressing TSH secretion. Intervention with leptin replacement can prevent fasting-induced changes in TSH, suggesting that leptin regulates TSH. Low leptin levels in sportsmen and sportswomen as well as in recreational runners are consistent with reduction in body fat, but are also influenced by the presence of low insulin, hypothyroxemia, and elevated cortisol levels. These metabolic adaptations to chronic energy deficits indicate a role in leptin regulation. A study within the general population found that activity levels and leptin were significantly negatively associated in both sexes. Circulating ghrelin levels, however, do not change during energy expenditure.
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PMID:Leptin TRH and ghrelin: influence on energy homeostasis at rest and during exercise. 1617 89

In adult patients weight gain is a frequent complaint of hyperprolactinaemia and it has been associated with a high prevalence of obesity. Normalization of prolactin (PRL) levels result in weight loss. The nature of this link is poorly defined. In this report we describe a 14 year-old female with primary amenorrhea and persistent progressive weight gain. The patient's height, weight and BMI were 152 cm, 70 kg, and 30.3 kg/m2, respectively. Basal hormonal investigation showed normal free thyroxin, TSH, IGF-I, cortisol and ACTH values. Serum PRL level was very high (16,278 mIU/l; normal range 63-426 mIU/l). Magnetic resonance imaging scan showed the presence of a pituitary microadenoma. Treatment with the non-selective dopamine agonist pergolide caused a significant reduction of serum PRL concentration with a remarkable decrease of body weight. During follow-up, repeat MRI scan revealed disappearance of the microadenoma. The reduction of the daily dose of pergolide was associated with an increase of serum PRL with significant weight gain. A further reduction of body weight was subsequently observed with an increase of pergolide dosage. Serum PRL measurement may be useful as part of the endocrine work-up of obese children with a history of unexplained recent weight gain, especially if associated with pituitary-gonadal axis dysfunction. The relationship between PRL secretion and weight change needs to be examined in prospective larger studies.
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PMID:Reversible weight gain and prolactin levels--long-term follow-up in childhood. 1627 71

Serum thyroid parameters show substantial inter-individual variability, in which genetic variation is a major factor. Findings in patients with subclinical hyper- and hypothyroidism illustrate that even minor alterations in serum thyroid function tests can have important consequences for a variety of thyroid hormone-related clinical endpoints, such as atherosclerosis, bone mineral density, obesity, and heart rate. In the last few years, several studies described polymorphisms in thyroid hormone pathway genes that alter serum thyroid function tests. In this review, we discuss the genetic variation in the TSH receptor and iodothyronine deiodinases. We discuss the possible consequences of these studies for the individual patient and also the new insights in thyroid hormone action that can be obtained from these data.
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PMID:Genetic variation in thyroid hormone pathway genes; polymorphisms in the TSH receptor and the iodothyronine deiodinases. 1706 80


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