Purging behavior modulates the relationships of hormonal and behavioral parameters in women with eating disorders.

BACKGROUND/AIMS: There is ample consensus that there is a neurophysiological basis for eating disorders (ED). Traits of personality translate into behavioral traits, purging being a well-defined transversal example. The direct implication of steroid hormones on ED has seldom been studied, despite their effects on behavior. METHODS: After psychological interview analysis, 57 ED female patients (31 purgative and 26 nonpurgative) and 17 female controls were studied. Metabolic parameters and analysis of androgen, estrogen and glucocorticoid hormones were determined in parallel to the psychopathological profile (EDI-2 and SCL-90-R) and anthropometric measurements. RESULTS: Psychometric tests showed clear differences between ED and controls, but there were few hormonal-metabolic significant differences. In purgative ED there were repeated (significant) positive correlations with corticosteroid-binding globulin (CBG) and negative correlations with sex hormone-binding globulin (SHBG) versus eating and general psychopathology. In nonpurging ED there were positive correlations for deoxycortisol, free fatty acids and albumin and negative for aspartate aminotransferase and psychopathological traits. CONCLUSION: The data suggest that CBG/corticosteroids and sexual hormones/SHBG are involved in purging behavior and its psychopathology and severity scores. Correlations of selected psychometric data and the CBG/SHBG levels in purging may eventually result in clinical markers. This approach may provide additional clues for understanding the pathogenesis of ED.

Oleoyl-estrone is a precursor of an estrone-derived ponderostat signal.

Oleoyl-estrone (OE) is a powerful anti-obesity compound that decreases food intake, decreases insulin resistance and circulating cholesterol. OE stimulates a severe loss of body fat by decreasing adipose tissue lipid synthesis and maintaining lipolysis. Therefore, the body economy loses lipid energy because energy expenditure is maintained. This study analyses the discrepancy between OE effects and the distribution of labelled OE in plasma. Estrone radioimmunoassay of organic solvent plasma extracts of rats treated with OE showed the massive presence of acyl-estrone, but saponification did not release estrone, but containing similar unknown compound. Analysis of label distribution in plasma after oral gavages of (3)H-OE showed the presence of a more hydrophilic compound than OE or any estrogen as well as (3)H(2)O, formed from (3)H-OE in the acidic stomach medium. OE was not attached to a specific transporter in plasma. Through serum HPLC analysis we found W, a labelled derivative more hydrophilic than OE or estrone. The results were confirmed using (14)C-OE. HPLC-MS/MS studies showed that plasma OE levels were one order of magnitude lower than those of W. When liver cell cytosols from rats laden with (3)H-OE were incubated with nuclei from untreated rats, the OE-derived label (i.e., Ws) was found attached to nuclear DNA. Neither estradiol nor estrone interfered with its binding. W is a fairly hydrophilic compound of low molecular weight containing the estrone nucleus, but it is not an ester because saponification or esterases do not yield estrone as OE does. It is concluded that OE acts through its conversion to W, its active form; which binds to a nuclear receptor different from that of estrogen. The estimated W serum levels are proportional to the pharmacological OE effects in vivo. We postulate W as a new type of hormone that exerts the full range of in vivo effects thus far attributed to OE. The full identification of W is anticipated to open the way for the development of new OE-like anti-obesity drugs.

Oleoyl-estrone increases adrenal corticosteroid synthesis gene expression in overweight male rats.

Oleoyl-estrone (OE) induces a marked loss of body fat in rats by maintaining energy expenditure, body protein and blood glucose despite decreasing food intake. OE increases glucocorticoids, but they arrest OE lipid-mobilization. We studied here whether OE induces a direct effect on adrenal glands function as part of this feedback regulation. Dietary overweight male rats were given oral 10nmol/g OE gavages for ten days. A group (PF) of pair-fed to OE rats, and controls received vehicle-only gavages. OE rats lost slightly more body than PF, but had larger adrenal glands. Tissue corticosterone levels, and gene expressions for glucocorticoid-synthesizing enzymes were increased in OE versus controls and PF; thus, we assumed that adrenal growth affected essentially its cortex since OE also lowered the expression of the medullar catecholamine synthesis enzyme genes. Serum corticosterone was higher in PF than in OE and controls, but liver expression of corticosteroid-disposing steroid 5alpha-reductase was 3x larger in OE than PF and controls. Circulating glucocorticoids changed little under OE, in spite of higher adrenal gland and liver content, hinting at modulation of glucocorticoid turnover as instrumental in their purported increased activity. In conclusion, we have observed that OE considerable enhanced the expression of the genes controlling the synthesis of glucocorticoids from cholesterol in the rat and increasing the adrenal glands' corticosterone, size and cellularity, but also the liver disposal of corticosteroids, suggesting that OE increases corticosterone synthesis and degradation (i.e. serum turnover), a process not driven by limited energy availability but directly related to the administration of OE.

Maternal treatment with oleoyl-estrone induces resistance to lipid accrual in their descendants.

OBJECTIVE: To determine whether treatment of rat dams with oleoyl-estrone (OE) has an effect on the offspring's long-term response to diet restriction during lactation. METHODS AND PROCEDURES: Control, OE-treated, and diet-restricted dams were treated up to day 15 of lactation. Changes in food intake and body weight were recorded for dams and their pups. After weaning, pups received a 4-week standard diet followed by a 4-week period of high-fat diet. Lipid, protein, and energy content of pups plus energy intake and efficiency. Serum metabolites (glucose, urea, and cholesterol) and serum hormones (adiponectin, leptin, insulin, and sexual hormones). RESULTS: Neither pups from dams in the OE-treated nor in the diet-restricted group showed significant changes in weight, though these two groups ingested 79% of food ingested by controls. At weaning, the pups from OE-treated rats were smaller than those of the control or diet-restricted groups. These pups maintained the differences in size and lipid content during the 4-week standard-diet period, whereas pups from diet-restricted dams showed a sharp decrease in their lipid content. During the 4 weeks of high-fat diet, the male offspring from OE-treated dams increased the difference in lipid content in relation to the pups from control dams whereas in females the differences decreased. Female offspring from diet-restricted dams showed the most marked changes in metabolite and hormone levels in relation to controls. DISCUSSION: Treatment of lactating dams with OE programs the metabolic response of their offspring to resist the challenge of a high-fat diet that would lead to obesity in adulthood.

Treatment of pregnant rats with oleoyl-estrone slows down pup fat deposition after weaning.

BACKGROUND: In rats, oral oleoyl-estrone (OE) decreases food intake and body lipid content. The aim of this study was to determine whether OE treatment affects the energy metabolism of pregnant rats and eventually, of their pups; i.e. changes in normal growth patterns and the onset of obesity after weaning. METHODS: Pregnant Wistar rats were treated with daily intragastric gavages of OE in 0.2 ml sunflower oil from days 11 to 21 of pregnancy (i.e. 10 nmol oleoyl-estrone/g/day). Control animals received only the vehicle. Plasma and hormone metabolites were determined together with variations in cellularity of adipose tissue. RESULTS: Treatment decreased food intake and lowered weight gain during late pregnancy, mainly because of reduced adipose tissue accumulation in different sites. OE-treated pregnant rats' metabolic pattern after delivery was similar to that of controls. Neonates from OE-treated rats weighed the same as those from controls. They also maintained the same growth rate up to weaning, but pups from OE-treated rats slowed their growth rate afterwards, despite only limited differences in metabolite concentrations. CONCLUSION: The OE influences on pup growth can be partially buffered by maternal lipid mobilization during the second half of pregnancy. This maternal metabolic "imprinting" may condition the eventual accumulation of adipose tissue after weaning, and its effects can affect the regulation of body weight up to adulthood.

Oleoyl-estrone treatment to late pregnant and mid-lactating rats affects the expression of lipid metabolism genes.

The purpose of this study was to determine whether OE treatment affects the expression of genes related to lipid metabolism under two physiological conditions: late pregnancy and mid-lactation, both characterized by lipid mobilization. Samples of periovarian and retroperitoneal adipose tissue from 21-day pregnant or 15-day lactating dams were used. The expression of LPL, FATP1, FABP4, HSL, ACC1, FAS, PEPCK, GLUT4, PDK4, SREBP1c, adiponutrin and leptin, were compared with their expression in virgin rats. In pregnant rats, FABP4, HSL, PEPCK and PDK4 were over expressed in the periovarian site compared to virgin rats, whereas adiponutrin, FAS, GLUT4 and SREBP1c were underexpressed; the retroperitoneal fat depot showed a similar pattern but ACC1 and leptin were also underexpressed. OE treatment caused a generalized decrease in gene expression in both adipose depots. In lactating dams, the gene expression profile at the periovarian depot was similar to that observed in pregnant rats. OE treatment mimicked the trend observed in pregnant rats, although the intensity of the gene expression changes was lower. After OE treatment, the retroperitoneal adipose depot showed a completely different pattern since the values were close to those of virgin rats. These results corroborate that OE effects in adipose tissue, lowering lipids and depressing their metabolism, already described under other physiological situations, can be also found in late pregnancy and lactation.

Regulation and biochemistry of mouse molybdo-flavoenzymes. The DBA/2 mouse is selectively deficient in the expression of aldehyde oxidase homologues 1 and 2 and represents a unique source for the purification and characterization of aldehyde oxidase.

Mouse molybdo-flavoenzymes consist of xanthine oxidoreductase, aldehyde oxidase (AOX1), and two recently identified proteins, AOH1 and AOH2 (aldehyde oxidase homologues 1 and 2). Here we demonstrate that CD-1, C57BL/6, 129/Sv, and other mouse strains synthesize high levels of AOH1 in the liver and AOH2 in the skin. By contrast, the DBA/2 and CBA strains are unique, having a selective deficit in the expression of the AOH1 and AOH2 genes. DBA/2 animals synthesize trace amounts of a catalytically active AOH1 protein. However, relative to CD-1 animals, an over 2 log reduction in the steady-state levels of liver AOH1 mRNA, protein, and enzymatic activity is observed in basal conditions and following administration of testosterone. The DBA/2 mouse represents a unique opportunity to purify AOX1 and compare its enzymatic characteristics to those of the AOH1 protein. The spectroscopy and biochemistry of AOX1 are very similar to those of AOH1 except for a differential sensitivity to the non-competitive inhibitory effect of norharmane. AOX1 and AOH1 oxidize an overlapping set of aldehydes and heterocycles. For most compounds, the substrate efficiency (V(max)/K(m)) of AOX1 is superior to that of AOH1. Alkylic alcohols and acetaldehyde, the toxic metabolite of ethanol, are poor substrates of both enzymes. Consistent with this, the levels of acetaldehyde in the livers of ethanol administered CD-1 and DBA/2 mice are similar, indicating that neither enzyme is involved in the in vivo biotransformation of acetaldehyde.

Alteraciones hormonales en mujeres jóvenes con obesidad mórbida / Hormonal alterations on young morbid obese women

FUNDAMENTO: La obesidad humana es una enfermedad de amplia distribución que presenta una considerable variabilidad en su gravedad, manifestaciones metabólicas y endocrinas y etiología. En el presente estudio hemos determinado si en mujeres adultas jóvenes la obesidad mórbida sin complicaciones afecta con diferente intensidad los valores circulantes de hormonas que se ha postulado que intervienen en el desarrollo y mantenimiento de la obesidad. SUJETOS Y MÉTODO: Se estudiaron y determinaron los valores circulantes medios (desviación estándar [DE]) de las hormonas y proteínas relacionadas con el control del peso corporal en 20 mujeres obesas mórbidas (índice de masa corporal, 52,6 [8,3] kg/m2) y 10 controles de peso normal (índice de masa corporal 19,9 [2,1] kg/m2) de edades similares. RESULTADOS: En las mujeres obesas se evidenciaron concentraciones más altas de insulina y leptina, y más bajas de cortisol y de la globulina que se une al cortisol (CBG). No se apreciaron diferencias para la tiroxina libre, hormona estimuladora del tiroides, estrona libre, acilestrona y sulfato de deshidroepiandrosterona. CONCLUSIONES: Los resultados indican que la obesidad mórbida implica la alteración de los principales sistemas hormonales que controlan la disponibilidad de energía y la respuesta a los retos externos, con la notable excepción del tiroides. Hay claras alteraciones en la insulina y leptina mientras que los cambios en el cortisol pueden estar correlacionados con factores distintos a la obesidad. Los valores de acilestrona menores de lo esperado apuntan a un posible déficit de esta señal de ponderostato en las mujeres obesas. La edad relativamente joven de las mujeres del estudio puede ayudar a explicar la relativa suavidad de los cambios hormonales observados (AU)