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)

A variety of recent literature suggests that brain gamma-aminobutyric acid (GABA) plays an important role in the control of feeding. One such line of evidence is that pharmacological inhibition of brain GABA transaminase (GABA-T) produces dose-dependent anorexia in otherwise normal rats. To determine the generality of these findings we tested the ability of the GABA-T inhibitor ethanolamine-O-sulfate (EOS), to produce anorexia in three animal models of obesity: rats with medial hypothalamic lesions, rats exposed to palatable foods or Zucker fatty rats. Following intracisternal injection of 100, 200 or 400 micrograms EOS, all three models of chronic overeating showed dose-dependent anorexia of similar magnitude and duration to that seen in appropriate controls. These observations provide empirical support for previous suggestions that treatments which enhance brain GABA neurotransmission merit investigation for their potential use in treating excess energy consumption.
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PMID:Anorectic potency of inhibiting GABA transaminase in brain: studies of hypothalamic, dietary and genetic obesities. 653 93

Fifteen patients with idiopathic hirsutism, who had no attenuated adrenal hyperplasia, obesity, enlarged ovaries, or amenorrhea, were studied. Excessive androgen secretion by adrenal tissue was suggested by the finding of increased levels of dehydroepiandrosterone sulfate, which decreased after dexamethasone administration but did not change after human chorionic gonadotropin (hCG) injection. Excessive androgen secretion by ovarian tissue was suggested by the finding that testosterone and androstenedione levels were elevated, correlated significantly with the levels of luteinizing hormone, decreased with administration of estrogen-progestagen, and increased after hCG injection. Notably, free testosterone levels, which were significantly increased, were only partially suppressed during dexamethasone or estrogen-progestagen administration. These results provide further evidence that both the adrenals and the ovaries secrete androgens excessively in patients with idiopathic hirsutism.
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PMID:Evidence of excessive androgen secretion by both the ovary and the adrenal in patients with idiopathic hirsutism. 680 96

Virilization in women is associated with increased production of testosterone as well as a variety of androgenic prehormones, including androstenedione, androstenediol, DHEA, DHEA-sulfate, dihydrotestosterone and androstanediol. Of these hormones, it is likely that testosterone is the androgen which initiates a series of androgen-receptor mediated events resulting in stimulation of 5 alpha reductase in the skin and hair follicles, producing dihydrotestosterone locally. The metabolism of testosterone to dihydrotestosterone within the hair follicle results in increased clearance of testosterone, however at the expense of hair follicle stimulation. Increased 5 alpha reductase of the skin and hair allows other prehormones to be metabolized to dihydrotestosterone and androstanediol, further stimulating the hair follicle (multiplier effect). In obese women, androgen production rates are elevated and SHBG levels are depressed, in many cases to the same magnitude as that observed in hirsute women. Increased androgen production rates in obesity, however, are associated with major increases in clearance rates of these androgens. Resultant androgen blood levels are even lower than observed in the non-obese population. It appears likely that adipose tissue is the site of the increased clearance rates and metabolism of prehormones to dihydrotestosterone and androstanediol. A delicate balance likely exists between production and clearance of these biologically active hormones. Minor aberrations in this balance may result in the increased incidence of hirsutism seen in the obese female population.
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PMID:A comparison of androgen production and clearance in hirsute and obese women. 688 88

The study included 191 patients with obesity, atherosclerosis, diabetes mellitus, endometrial cancer, breast cancer and healthy subjects of various age. Somatomedin activity was determined by incorporation of radioactive natrium sulfate in vitro into the cartilage of female rats. The results of the study showed that somatomedin activity was not changed in subjects with normal metabolic parameters and ranged from 0.47 to 0.69 U/ml. In patients with diabetes mellitus, atherosclerosis and obesity accompanied by increased blood concentration of cholesterol and triglycerides, somatomedin activity rose up to 1.36- 1.62 U/ml. In patients with breast and endometrial cancer somatomedin activity was also increased, particularly in those with hypercholesterolemia and hypertriglyceridemia (3.04 U/ml for breast cancer patients and 2.20 U/ml for endometrial cancer patients). Theoretically, this may promote proliferation of somatic cells and thus contribute to tumor processes in oncological patients whose pool of cells is extremely sensitive to mitogenic agents.
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PMID:Interrelation between lipidemia and somatomedin activity in cancer and age-associated pathology. 713 38

Levels of serum androgens and sex hormone binding globulin (SHBG) were measured in 20 obese Pima Indian females aged 19-44 and compared with those of normal-weight Caucasians aged 20-46. The Pima exhibited significantly decreased SHBG compared to Caucasians, but a strong effect of age on androgen levels rendered mean comparisons useless. Androstenedione (A) and dehydroepiandrosterone-sulfate (DHEA-S) decreased significantly, and testosterone (T) declined slightly with age in the Pima, whereas these androgens showed no significant decreases in Caucasians for this age range. A possible relationship of androgens to the Pima female's propensity for android obesity as well as possible effects of obesity on SHBG, and aging is discussed.
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PMID:Serum Androgens and sex hormone binding globulin in obese Pima indian females. 719 23

It has been shown that in vitro calcium channel blockers may regulate insulin secretion, and in vivo studies have demonstrated that they can reduce the degree of hyperinsulinemia and ameliorate the insulin-resistant state in subjects (particularly men) with obesity and hypertension. It is also commonly accepted that hyperinsulinemia may be an important factor responsible for the development of hyperandrogenism in obese women with polycystic ovarian syndrome (PCOS). We, therefore, investigated whether the administration of nitrendipine, a widely used calcium channel blocker, may improve both insulin levels and hyperandrogenism in a group of seven insulin-resistant hyperinsulinemic women with obesity and PCOS. They were treated for 7-8 days with oral nitrendipine (10 mg, twice daily) or placebo using a double blind, cross-over design. Before and after treatment, blood samples were obtained for androgen and sex hormone-binding globulin determinations, and an oral glucose tolerance test was performed, measuring glucose and insulin. Both nitrendipine and placebo failed to decrease basal and stimulated insulin levels. Moreover, no significant variations in testosterone, dehydroepiandrosterone sulfate, or sex hormone-binding globulin concentrations were observed after either treatment. Therefore, these data fail to support previous suggestions that calcium channel blockers may play a role in the treatment of hyperandrogenism and hyperinsulinemia in obese women with PCOS.
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PMID:Nitrendipine treatment in women with polycystic ovarian syndrome: evidence for a lack of effects of calcium channel blockers on insulin, androgens, and sex hormone-binding globulin. 759 49

As so many variables can affect obesity (age, genetics, health status), new directions, other than reducing or altering diet, are being pursued in controlling obesity in our society. Both dehydroepiandrosterone (DHEA) and GH have reported antiobesity effects; thus, the possible interaction of these hormones was investigated in genetically lean, obese, and meat-type cross-bred male pigs (boars) administered implants that released 0, 2, or 4 mg/day recombinant porcine GH (pGH) for 42 days. Subcutaneous fat was determined by measurement of back fat depth at 2-week intervals, and blood samples were obtained 0, 7, 14, 28, and 42 days post-implant. The weight of perinephrenic fat, an index of abdominal fat, was obtained at death. The obese line had higher DHEA/DHEA sulfate (DHEA-SO4) serum concentrations than the lean and cross-bred boars. Treatment with pGH reduced sc and perinephrenic fat in all lines at both doses (P < 0.01). There was no relationship between day 42 concentrations of DHEA/DHEA-SO4 and indexes of obesity. Concentrations of DHEA/DHEA-SO4 were decreased by pGH treatment (P < 0.01) by days 7-14 in all genetic lines. Concentrations of insulin-like growth factor I, insulin-like growth factor II, and insulin were increased with pGH treatment in all lines (P < 0.01). The a priori hypothesis that increases in these peptides would stimulate gonadal steroidal synthesis (as demonstrated in vitro) and result in elevated DHEA/DHEA-SO4 concentrations and reduced obesity was not supported by pGH-induced decreases in DHEA/DHEA-SO4. Insulin concentrations were elevated 7-14 days postimplant in all lines (P < 0.01), then declined in the later stages of the trial. Insulin concentrations and DHEA/DHEA-SO4 concentrations were inversely related (r = -0.59; P < 0.05); this may indicate that with elevated insulin levels, DHEA/DHEA-SO4 is decreased and has a limited opportunity to affect obesity. Although the administration of DHEA may reduce obesity, the lipolytic action of pGH does not appear to be through increased circulating concentrations of DHEA/DHEA-SO4.
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PMID:Obesity and dehydroepiandrosterone/dehydroepiandrosterone sulfate relationships in lean, obese, and meat-type cross-bred boars: responses to porcine growth hormone. 762 65

Polycystic ovary (PCO) syndrome is strongly associated with insulin resistance and the accompanying adverse metabolic profile. To distinguish the mechanisms of this association, we determined the interactions of PCO with obesity and the influence of ameliorating direct androgenic actions via short-term treatment with the antiandrogen flutamide. Insulin sensitivity was determined by the hyperinsulinemic euglycemic clamp in groups of lean and obese PCO women and weight-matched controls. Compared with control values, insulin-mediated glucose utilization in PCO women was significantly lower in lean (1.96 +/- 0.17 v 1.24 +/- 0.10, P < .01) and obese (1.23 +/- 0.18 v 1.03 +/- 0.09 mmol/m2/min, P < .01) subjects. ANOVA indicated that the effects of obesity and androgenicity are independent and additive. In both lean and obese PCO women, treatment with flutamide for 1 or 3 months markedly improved the clinical and biochemical androgenic features, but did not significantly influence the overall insulin sensitivity. A large disparity between individuals in the response to treatment correlated significantly with a simultaneous reduction in plasma levels of dehydroepiandrosterone sulfate (DHEA-S). Thus in women, PCO and obesity exert synergistic effects on insulin resistance. The decreased insulin sensitivity is mediated via indirect androgenic actions or nonandrogenic mechanisms. In some individuals, a direct effect of androgens might have been masked by a decrease in DHEA-S levels.
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PMID:Insulin sensitivity and antiandrogenic therapy in women with polycystic ovary syndrome. 772 77

A radiochemical method for selective measurement of postheparin lipase activities was adapted to analyze lipoprotein lipase and hepatic lipase in preheparin plasma. The assay sensitivity was increased about four-fold by doubling both the volume of plasma used and the volume of lipolytic products taken for liquid scintillation counting, and was further improved by increasing the incubation period by 50% to 90 min. Rabbit antiserum to human hepatic lipase was unsuitable for the selective measurement of lipoprotein lipase because of apparent endogenous lipolytic activity. Preheparin hepatic lipase, however, was sensitive to inactivation by sodium dodecyl sulfate (SDS), the inhibition being greatest (> 90%) for plasma incubated with an equal volume of 40 mmol/L SDS. Intra- and interassay CVs for the two enzymes were 12.5-14.6% and 17.4-19.7%, respectively. In a cross-sectional study of 84 healthy subjects, pre- and postheparin hepatic lipase activities were higher in men than women, were correlated with indices of obesity, and were significantly correlated with one another, which explained the association of the former with plasma concentrations of high-density lipoprotein (HDL), HDL2, and small, dense low-density lipoproteins. There was no significant relationship between pre- and postheparin lipoprotein lipase activities, but the former were correlated with plasma concentrations of free fatty acids (FFA) and very-low-density lipoprotein. Apparently, preheparin activities of hepatic lipase, but not of lipoprotein lipase, may be a useful measure of the physiological function of "whole body" enzyme activity in cross-sectional and metabolic studies, where heparinization is not possible. Preheparin lipoprotein lipase activities, however, may reflect displacement of the enzyme by FFA and subsequent binding to remnants of triglyceride-rich lipoproteins.
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PMID:Measurement and physiological significance of lipoprotein and hepatic lipase activities in preheparin plasma. 788 16

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


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