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

To examine hormonal status in obese, gynecologically normal women we studied 25 regularly menstruating, massively obese (mean weight, 120 kg) women participating in a weight reduction program and 25 age-matched normal weight (mean weight, 60 kg) women. Serum 17 beta-estradiol (E2), estrone (E1), androstenedione (A), dehydroepiandrosterone sulfate, testosterone, LH, FSH, PRL, and cortisol concentrations were measured during the follicular phase of the menstrual cycle. Waist to hip ratio and abdominal fat cell size were measured at the beginning of the study. The serum levels of E2 (P less than 0.04) as well as those of A, SHBG, and LH (P less than 0.002) were lower in the obese group. Consequently, the testosterone to SHBG ratio and the E1 to A ratio were higher and the LH to FSH ratio was lower in this group. Waist to hip ratio did not correlate with the levels of circulating hormones or SHBG, but an inverse correlation was found between abdominal fat cell size and A as well as the LH to FSH ratio in the nonhirsute women of the obese group. Subsequent to moderate weight reduction (13.2 kg), serum A and E1 levels (P less than 0.01) increased, and serum cortisol levels decreased (P less than 0.001). Thus, massive obesity is associated with abnormalities in hormonal balance in gynecologically symptomless women, there being an association between E1, E2, A, LH, cortisol, and relative weight and/or abdominal fat cell size.
 ...
PMID:Sex steroid, gonadotropin, cortisol, and prolactin levels in healthy, massively obese women: correlation with abdominal fat cell size and effect of weight reduction. 309 52

To determine whether endogenous opiates mediate hyperactivity in food restricted hamsters and serotonergic fibers innervating the hippocampus mediate hypoactivity in obese hamsters, food restriction and high-fat diet supplementation were used to produce significant body fat changes (8 vs. 21%). The levels and pattern of spontaneous running were examined after IP saline or naloxone HCl (20 mg/kg) and following the infusion of vehicle and 5,7-dihydroxytryptamine creatine sulfate (4 micrograms/2 microliters) into rostromedial septum of mature female hamsters. Septum-medial preoptic area (POA), hippocampus, hypothalamus, and cortex were dissected from the three groups as well as from two additional groups of hamsters receiving vehicle or neurotoxin. Concentrations of serotonin, norepinephrine, and dopamine were measured in these tissues by HPLC method. Fat-fed hamsters were hypoactive relative to food-restricted hamsters. Naloxone had no significant effect on running behavior. Serotonin neurotoxin increased the running activity of fat-fed hamsters to the level displayed by control hamsters by increasing the number of runs, the total activity level, the speed of running and by decreasing the duration of pauses. Neurotoxin led to selective deletion of serotonin in the hippocampus (77%) and parietal cortex (50%). Serotonergic fibers innervating the hippocampus thus appear to mediate the hypoactivity that is induced by dietary obesity in mature hamsters. Since serotonin mediates some other manifestations of aging, and slow weight increases characterize mid-portion of hamster life span, we hypothesize that serotonergic mediation of hypoactivity is another manifestation of aging.
 ...
PMID:Hippocampal serotonin mediates hypoactivity in dietarily obese hamsters: a possible manifestation of aging? 325 81

A summary of the lipoprotein and carbohydrate risk factors for coronary heart disease associated with use of oral contraceptives is followed by a discussion of the methodological difficulties in measuring them, and then by a description of the properties of commonly used oral steroids. Impaired glucose tolerance, high insulin levels, reduced HDL cholesterol and increased LDL cholesterol and VLDL triglycerides are features of coronary heart disease, diabetes, obesity and use of oral contraceptives. A more accurate assessment of glucose tolerance may be measurement of the plasma C-peptide of insulin. Lipid risk factors are subject to wide individual variation as well as special difficulties for pill users. For example, the convenient dextran sulfate method of precipitating HDL, from which the LDL value is calculated, may not be accurate for pill takers because of elevated triglycerides. Even assay of apolipoprotein B is subject to this distortion. If apolipoprotein methods can be standardized, assay of apolipoprotein A1, corresponding to the HDL2 subclass, may be appropriate. Progestins of the gonane class, such as levonorgestrel, because of their androgenic activity, induce changes in lipid risk factors in women similar to those of men. The net effect of the combination of estrogen and progestin is what matters, however. Although progestin-only pills have no effect on carbohydrate metabolism, combined pills decrease glucose tolerance with time, induce hypertriglyceridemia, and oppose the tendency of the estrogen to increase HDL. Norethindrone or other estrane compounds have less impact. Data on triphasics are sparse, but suggest a lesser effect also. New progestins with lower androgenic effects are being developed, although they may confer the added risk of increased triglycerides. Parenteral steroid administration or use of natural hormones are potential solutions.
 ...
PMID:Oral contraceptives and coronary heart disease: modulation of glucose tolerance and plasma lipid risk factors by progestins. 328 33

This study examined the prevalence of both basal and glucose-stimulated hyperinsulinemia and acanthosis nigricans (AN) as well as the relationship between insulin and androgen levels in hyperandrogenic women. Sixty-two women who had an elevation of 1 or more plasma androgen levels were studied. The results in these women, grouped for analysis on the basis of obesity and ovulatory status, were compared to those in 36 control women of similar ages and weights. The anovulatory hyperandrogenic women had the clinical and biochemical features of the polycystic ovary syndrome (PCO). Oral glucose tolerance tests were performed with measurement of glucose, insulin, sex hormone-binding globulin (SHBG), and total and non-SHBG-bound sex steroid levels. AN was present in 29% of the hyperandrogenic women, the majority of them obese. Fifty percent of obese PCO women had AN, but they did not otherwise differ from PCO women lacking this dermatological change. Only women with PCO had significant hyperinsulinemia independent of obesity, and obese PCO women with AN had the highest serum insulin levels. Plasma glucose values during the oral glucose tolerance test were significantly increased in obese PCO women independent of the presence of AN, and 20% of these women had frank impairment of glucose tolerance. Ovulatory hyperandrogenic women had normal insulin levels and glucose tolerance. Obese and nonobese women had different relationships between sex steroid and insulin levels; obese women had significant correlations between insulin and non-SHBG testosterone levels (r = 0.30; P less than 0.05), whereas nonobese women had significant correlations between insulin and FSH (r = 0.40; P less than 0.01), dehydroepiandrosterone sulfate (r = 0.33; P less than 0.05), and SHBG (r = 0.37; P less than 0.05) levels, suggesting that the mechanisms underlying the association between sex steroid and insulin levels are complex. These findings suggest that 1) only women with PCO have hyperinsulinemia independent of obesity; hyperinsulinemia is not a feature of hyperandrogenic states in general; 2) AN is a common finding in obese hyperandrogenic women, particularly those with PCO; 3) only obese PCO women are at risk for impairment of glucose tolerance, independent of the presence of AN, suggesting that the negative impact of PCO and obesity on insulin action is additive; and 4) PCO women with AN can be considered as a subgroup of PCO and do not appear to have a distinct endocrine disorder.
 ...
PMID:Characterization of groups of hyperandrogenic women with acanthosis nigricans, impaired glucose tolerance, and/or hyperinsulinemia. 330 51

To evaluate the effect of weight loss and diet therapy on plasma sex hormone behavior in male obesity, 9 men with a BMI of 43.4 +/- 6.3 participated in an 8-week semistarvation program [whose energy content ranged from 320 to 500 k calorie/day (proteins 44 to 60 g and carbohydrates 54 to 81 g per day)] followed by a two-week hypocaloric (1000 k calorie/day) refeeding. In basal conditions, obese patients presented higher estrogen and lower dehydroepiandrosterone sulphate, testosterone (total and free) and sex-hormone binding globulin concentrations with respect to a group of control normal-weight subjects. Cumulative weight loss was 23.9 +/- 3.6 kg after semistarvation and 24.4 +/- 4.8 kg after refeeding (p = NS). A significant increase in testosterone, free testosterone and dehydroepiandrosterone sulfate was observed throughout the study, irrespective of dietary intake. A transient increase occurred in estrone levels while 17B-estradiol did not change. Gonadotropins and sex-hormone binding globulin values remained unaltered. No relationship was found between sex hormones and dietary energy content or composition. Daily urine free cortisol, which was used as a parameter of adrenal function, fell approximately 50% during semistarvation but returned to baseline values after refeeding. These results show that in massively obese patients weight loss per se may partially reverse sex hormone abnormalities but not sex-hormone binding globulin concentrations. It remains to be determined whether the return to "normal weight" can normalize steroid metabolic derangements in the obese man.
 ...
PMID:Weight loss and sex steroid metabolism in massively obese man. 337 60

Altered thyroid hormone metabolism is known to be an important factor contributing to the defective expression of thermogenesis in the obese mouse, and the action of zinc on thyroid hormone conversion may be an important factor in the energy metabolism of obesity. The effects of zinc and thyroxine treatment on dietary-obese mice were examined. The dietary-obese mice were successfully induced by high-fat diet (80% fat), and every mouse was administered daily 1.25 mg zinc sulfate and/or 5 micrograms thyroxine. After 8 weeks of treatment, serum zinc, serum triacylglycerols and body fat composition were determined. On high-fat diets, fat deposition was found in male mice treated with zinc sulfate. However, when mice were treated with zinc and thyroxine at the same time, serum triacylglycerols and body fat composition decreased significantly on both basal and high-fat diets. When mice were treated with thyroxine alone, body fat composition decreased significantly, but there was no significant effect on serum triacylglycerols on either diet. Obesity was significantly correlated with dietary fat, zinc and thyroid hormone. It is suggested that zinc may play an important role, through its action on thyroid hormone conversion and via insulin action, in the energy metabolism of dietary-obese mice.
 ...
PMID:Effects of zinc and thyroxine treatment on dietary-obese mice. 344 18

The effect of cholinomimetic stimulation by infusion of edrophonium chloride or muscarinic blockade by infusion of atropine sulfate on insulin and GIP secretion was studied in normal lean subjects during eu- and hyperglycemia. Cholinomimetic stimulation led to a slight non-significant increase and muscarinic blockade to a slight, non-significant suppression of both GIP and insulin. No modification of the insulin secretion pattern was observed under either condition during hyperglycemia. The effect of atropine infusion on fasting plasma insulin and GIP was subsequently studied in 11 obese patients and 10 lean subjects. Muscarinic antagonism by atropine led to a transient non-significant suppression of GIP and insulin in lean subjects, but to a significant, sustained suppression of these hormones in obese patients. Insulin and GIP levels were however, not suppressed to control values after atropine administration in obese patients. A positive correlation was found between fasting plasma insulin and maximal suppression of insulin attained during the 30 min following administration of atropine. It is concluded that part of the hyperinsulinemia observed in human obesity is under the control of the parasympathetic nervous system. An abnormal balance between sympathetic inhibitory and parasympathetic stimulatory tones on insulin secretion, as observed in the VMH lesioned rat, might be present in human obesity.
 ...
PMID:Effects of cholinergic stimulation and antagonism on plasma insulin concentration in lean and obese human subjects. 354 47

The overfed rat served as the animal model for examining the influence of obesity on the hepatotoxic and nephrotoxic potential of metabolically activated drugs, and acetaminophen served as the prototype drug. Weanling Sprague-Dawley rats were given a standard pellet diet or semisynthetic, energy-dense diet designed to produce obesity. After 24 weeks, when overfed rats outweighed controls by more than 50%, animals received 710 mg/kg of acetaminophen i.p., based on total body weight. Toxicity evaluation included biochemical signs of organ injury over the first 24 hr and histopathologic changes in tissue morphology at 48 hr. Both enzyme release (alanine aminotransferase into plasma, alkaline phosphatase into urine) and frank cellular necrosis in liver and kidney of obese rats greatly exceeded that in pellet-fed controls. Contributing to the potentiation of injury were higher peak plasma concentrations of acetaminophen in obese animals resulting from total body weight dosing. However, liver and kidney injury and mortality remained elevated when peak plasma concentrations were matched by fat-free mass dosing, indicating that increased toxicity also was related to obesity. Incomplete recovery of acetaminophen and metabolites from obese animals (45 vs. 71% in control rats) caused by a functional renal impairment made it impossible to determine the metabolic fate of acetaminophen in overfed animals from the analysis of urine collections. Drug products measured in urine were summed with amounts remaining in carcass at sacrifice, computed as terminal plasma concentrations times respective distribution volumes. These results showed obese rats to form more glucuronide and less sulfate conjugate than did pellet-fed controls, coinciding with clinical evidence for enhanced glucuronidation in obese humans.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Obesity as a risk factor in drug-induced organ injury: increased liver and kidney damage by acetaminophen in the obese overfed rat. 359 8

The current studies examine acetaminophen pharmacokinetics and biotransformation in obese animals for possible shifts in metabolic conjugation reactions. Obesity was produced in Sprague-Dawley rats with an energy-dense cafeteria feeding regimen. Acetaminophen half-life remained unchanged and apparent volume of distribution increased slightly in obese versus pellet-fed control rats following an ip dose of 287 mg/kg. However, obese animals exhibited lower plasma concentrations of acetaminophen sulfate and excreted less sulfate conjugate but more glucuronide conjugate in urine. Absolute clearance of acetaminophen from plasma was similar for both groups of rats but formation clearance of acetaminophen sulfate was lower and formation clearance of acetaminophen glucuronide and was higher than control in obese rats. Renal clearance of unchanged drug and both conjugated metabolites appeared to rise with the degree of obesity. The many parallels in acetaminophen disposition shared with the obese human show the overfed rat to be a promising model for metabolic and physiologic changes associated with human obesity.
 ...
PMID:Acetaminophen sulfation deficit in obese rats overfed an energy-dense cafeteria diet. 362 4

This review of the epidemiologic and endocrinologic literature aims to improve understanding of the etiology of premalignant breast disease. Although there are inconsistencies regarding the clinical symptoms defined as benign breast disease, there are 2 major clinical categories: cysts treated by aspiration and solid lesions treated by excision or incision biopsy. A necessary research approach is to determine which patients with benign breast disease have an increased risk of breast cancer and study them to determine whether they carry any endocrine or biologic stigmata. Epithelial hyperplasia is the lesion with greatest premalignant potential. Both population and case-control studies have examined the association between benign breast disease and the risk factors of age, reproductive history, family history of breast cancer, obesity, socioeconomic status, race, oral contraceptive use, and methylxanthines. No clear or consistent endocrine or hormonal abnormalities have been detected in women with benign breast disease. On the other hand, cyst fluid studies have revealed high amounts of androsterone sulfate and DHA-sulfate compared with serum levels. Carcinoembryonic antigen levels are highest in women with fibrocystic disease. At this point, it is unclear whther the progression from normal epithelium through atypia and hyperplasia and then in in situ carcinoma or invasive carcinoma is under hormonal control. Inconsistencies within the research literature may reflect the heterogeneity of conditions encompassed within the benign breast disease category. Since epithelial hyperplasia is likely a forerunner of breast cancer, such patients should be monitored to determine whether they exhibit a consistently abnormal pattern of hormonal production, e.g., subnormal androgen levels or elevation of free estradiol.
 ...
PMID:Epidemiology and endocrinology of benign breast disease. 390 25


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>