Effectiveness of estradiol in preventing and reversing obesity induced by ovariectomy and high-caloric diet in female rats.

Four experiments with 77 female Holtzman rats examined the effects of estradiol benzoate (EB) on food intake, body weight (BW), ano-nasal length, and BW/body length ratio in ovariectomized (OVX) and intact Ss maintained on control or high-fat diets and of OVX and intact Ss that had been reduced by deprivation. EB was highly effective in preventing the increase in food intake, BW, and ano-nasal growth after OVX; it was relatively ineffective in reversing BW gain after OVX. However, when ano-nasal length was also considered, BW was effective in returning OVX Ss to an appropriate BW for their increased ano-nasal length. Intact Ss fed a high-caloric diet did not exhibit an increased rate of ano-nasal growth, which indicates that the skeletal growth that occurred after OVX was not simply a result of increased food intake. It is concluded that EB modulates food intake and BW by multiple mechanisms, one of which is by modulating skeletal growth. The nature of the effect of EB on BW of intact Ss suggests that this effect occurs by still another mechanism. (13 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Variation of food intake and body weight with estrous cycle, ovariectomy, and estradiol benzoate treatment in hamsters (Mesocricetus auratus).

In 3 experiments with 46 female hamsters, food intake and body weight fluctuated systematically with the estrous cycle. Food intake and body weight were lowest when elevated endogenous estrogen levels were expected. Ovariectomized Ss gained a significant amount of body weight compared with sham-operated Ss. Replacement therapy with estradiol benzoate reduced the body weight and food intake of ovariectomized Ss relative to oil-injected, ovariectomized controls. Results are compared with similar data from rats; they support the concept that in females of both species estradiol operates to regulate food intake and body weight. (22 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Decrease in food intake following cortical spreading depression in static obese rats with ventromedial hypothalamic lesions.

Subjected 19 male and 23 female rats with ventromedial hypothalamic (VMH) lesions or with sham lesions to cortical spreading depression (CSD) 150 days after lesioning. Lesioned Ss showed a significantly lower food intake (as percentage of intake before CSD) than sham-lesioned Ss in the 14 days after CSD, but water intake did not differ between lesioned and sham-lesioned Ss. Both groups showed a slight decline in body weight, but lesioned Ss lost significantly more weight than sham-lesioned Ss. After 14 days, body weight, food intake, and water intake had returned to pre-CSD levels in both groups. Findings indicate that Ss with VMH damage are more sensitive to the effects of CSD than are normals and suggest that CSD acts to increase the activity of the VMH and to inhibit food intake, and this increase in activity is prolonged in VMH-lesioned Ss. (22 ref.) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Independent effects of estradiol on water and food intake.

Conducted 6 experiments to examine the effects of estradiol on ingestive behaviors of guinea pigs. Estradiol treatment was found to reduce water intake independently of its actions on food intake and body weight. In the 1st experiment, minimum intake and body weight of 17 intact female guinea pigs coincided with rupture of the vaginal membrane, the estimated time of ovulation. In Exp II, injections of 3 μg of estradiol benzoate (EB)/day to 7 ovariectomized females significantly depressed food intake, water intake, and body weight, compared with 7 Ss that received oil injections. Reducing food rations to 30% below ad lib levels in Exp III by itself had no significant effect on drinking in ovariectomized Ss. In Exp IV, therefore, ovariectomized females were first placed on a food ration 30% below ad lib levels and then injected daily with either 3 μg of EB or oil. Compared with oil injections, these EB injections significantly reduced water intake, while food intake did not decline significantly. Findings indicate that estradiol operates through different mechanisms to affect water intake and food intake. (40 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Suckling behavior and intake control in the developing rat pup.

Studied the behavioral development of suckling and intake control in 2 experiments with Charles River CD strain rat pups. Ss were observed at the initiation, during the course, and at the termination of suckling from their anesthetized mothers. Diet was delivered intraorally through a fine tongue cannula which enabled control of timing and volume. The control of diet intake and the behavior at termination of suckling showed correlated changes from 5 to 20 days of age. When deprived of suckling (and food and water) for 8 hr, 5- and 10-day-old Ss consumed large volumes of diet (10% of body weight or greater) and terminated suckling only in the presence of extreme gastrointestinal filling. These Ss were immediately lethargic and slept after intake termination. Five-day-old Ss persisted in reattaching to the nipple when manually stimulated; 10-day-old Ss eventually refused to reattach. In contrast, 20-day-old Ss consumed more moderate volumes of diet (5% of body weight). These Ss also remained awake for a period after feeding and engaged in the exploratory and grooming activities characteristic of adult rats at the termination of feeding. These observations demonstrate major changes in suckling behavior during development. They suggest that intake control processes shift from indirect to direct and become more effective and specifically food intake related in older pups. (20 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Induction of ob gene expression by corticosteroids is accompanied by body weight loss and reduced food intake

Genetic studies in mice have identified the ob gene product as a potential signaling factor regulating body weight homeostasis and energy balance. It is suggested that modulation of ob gene expression results in changes in body weight and food intake. Glucocorticoids are shown to have important metabolic effects and to modulate food intake and body weight. In order to test the hypothesis that these metabolic effects of glucocorticoids are linked to changes in the expression of the ob gene, ob mRNA levels were evaluated in rats treated with different glucocorticosteroids at catabolic doses and correlated to the kinetics of changes in body weight gain and food intake. Results from time course experiments demonstrate that adipose tissue ob gene expression is rapidly induced by glucocorticosteroids. This induction is followed by a concordant decrease in body weight gain and food consumption. These data suggest that the catabolic effects of corticosteroids on body weight mass and food intake might be mediated by changes in ob expression. Modulation of ob expression may therefore constitute a mechanism through which hormonal, pharmacological, or other factors control body weight homeostasis.     

Failure to obtain sex differences in development of obesity following ventromedial hypothalamic lesions in rats.

Gave 24 male and 24 female albino Charles River rats either a high-fat or a ground-food diet following ventromedial hypothalamic or sham lesions. After 63 days on 1 diet, diets were reversed for 27 days. Over 63 days (a) lesioned Ss of both sexes showed a significant increase in weight over their controls, (b) Ss on high fat gained more weight than those on ground food, and (c) there was no difference between the sexes in weight gain. When diets were reversed, lesioned Ss now on ground food maintained about the same weight as before reversal, while Ss switched to the high-fat diet rapidly increased their body weight to a point near that of Ss originally on the high-fat diet. Data indicate that there is no sex difference in weight gain following ventromedial lesions. It is suggested that previously reported differences result from (a) insufficient periods of observation, (b) offering unpalatable diets, or (c) the use of random-bred strains which increases variability of animal size and lesion placement. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Development of obesity in diabetic mice pair-fed with lean siblings.

Investigated the role of hyperphagia in the obesity of the diabetic mouse, C57BL/6J/db/db. Ingestion patterns and the amount of food for 25 diabetic mice were controlled by yoking their food intake to that of 16 nonobese siblings obtaining their food by barpressing. Over a period of 6 wks, young (initial ages were 28 days) pair-fed diabetic Ss accumulated 42% more body weight and approximately 5 times more extractable carcass lipid than did their siblings. Weight gain and absolute levels of carcass fat were reduced in food-restricted diabetic Ss compared with db Ss on unrestricted food intake. However, carcass fat as percentage of wet carcass weight was virtually identical in the restricted and unrestricted db rats (47.6 vs 49.6%). From these results it is concluded that the heightened adiposity of the diabetic mouse does not require hyperphagia for its expression and thus represents a metabolic obesity. (34 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Thyroxine treatment reduces the anorectic effect of estradiol in rats.

Examined a possible interaction between thyroxine and estradiol in the control of feeding in female Sprague-Dawley rats. 14 ovariectomized Ss were given daily injections of 9.8 μg/100 g of body weight of 1-thyroxine (TX). Another 14 Ss received 0.15 ml of saline (SAL) subcutaneously each day, and food intake was measured for both groups daily. After 15 days of treatment, 8 Ss from each group were also given a single injection of 6 μg of estradiol benzoate (EB), and the remaining 6 Ss of each group received peanut oil vehicle. It was found that TX-treated Ss showed a significantly smaller drop in food intake after EB than did SAL-treated Ss. This TX-induced decrease in responsiveness to EB may be related to effects of TX on general metabolism. (29 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Some effects of ovarian hormones on food intake and body weight in female rats.

Conducted 3 experiments with a total of 63 ovariectomized and 41 ovariectomized-adrenalectomized Sprague-Dawley rats in which ovarian steroids affected food intake and body weight. These effects were probably mediated by estradiol and progesterone, since these 2 hormones were more effective than their principal metabolites (estrone 5a-pregnane-3,20-dione, 5ai0regnane-3,20-dione, respectively) in altering the food intake and body weight of ovariectomized Ss. Estradiol seemed to affect food intake by lowering the set point about which body weight is regulated in a dose-dependent fashion. These actions of estradiol could be attenuated or completely blocked by concurrent injections of progesterone. Estradiol-treated ovariectomized Ss were far more responsive to the weight- and appetite-promoting actions of progesterone than were ovariectomized-adrenalectomized Ss, suggesting that the principal action of progesterone on energy balance may be to interfere with the effects of estradiol. (30 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Rats define different body weights depending on palatability and accessibility of their food.

Normal adult Long-Evans rats lived on powdered diets adulterated to contain as much as 1.6% quinine sulfate, on a palatable high-fat diet, or in Skinner boxes with 45-mg Noyes pellets available on FR schedules as high as FR-256. They maintained lower body weights over periods of months in proportion to the percentage of quinine adulteration or the FR. Ss on the high-fat diet overate as much and gained weight as rapidly as Ss recovering from food deprivation, and became moderately obese. Ss having become lean or obese contingent on the palatability or accessibility of their diet defended body weight by eating more in the cold, less when force-fed by gavage, and more to restore weight after food deprivation. Yet on chow they restored and defended body weights typical of Ss whose diet had been confined to commercially prepared chow. Results are inconsistent with motivational models that rigidly distinguish drive from incentive, that treat body weight changes as evidence for failure to regulate energy balance or body weight, or that rely exclusively on deprivation of food or reduction of body weight for definitions of need for calories. Instead, caloric homeostasis in rats may incorporate ecological constraints. (30 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Comparative effects of the selective estrogen receptor modulators (-)-, (+)- and (+/-)-Z bisdehydrodoisynolic acids on metabolic and reproductive parameters in male and female rats

Doisynolic acids are non-steroidal estrogenic compounds originally obtained from alkali fusion of estrone and equilenin. Z-bisdehydrodoisynolic acids (Z-BDDA) exhibit a low binding affinity accompanied by a disproportionately high biologic activity. Two experiments were designed to investigate the chronic effects of (+)-, (-)- and (+/-)-Z-BDDA and (+)-17beta-estradiol (E2) in male and female rats. The (+)-, (-)- and (+/-)-forms Z-BDDA were prepared and injected, daily for four to six weeks into male and female rats and changes in body weight, food intake, metabolic parameters, and reproductive parameters were investigated. Results from both experiments demonstrate that in male and female rats, (+)- and (+/-)-Z-BDDA had similar estrogenic effects on reproductive organ weight. Surprisingly, (-)-Z-BDDA did not induce the increase in uterine weight observed with (+)- and (+/-)-Z-BDDA and E2, demonstrating selective estrogen receptor modulation (SERM). Beneficial metabolic effects, although compound- and gender-specific, included a significant weight repression, reduction in cholesterol, reduction in blood glucose, and positive alterations in body fat distribution. Future research defining the optimal dosages of (-)-Z-BDDA that will maximize beneficial effects and minimize undesirable effects on reproductive tissues will lead to more efficacious treatment options for endocrine-responsive conditions in males and females.     

Effects of desalivation on drinking and air licking induced by water deprivation and hypertonic saline injections.

Previous studies show that desalivate (DS) rats drink more water than controls when maintained on a diet of dry food, but drink less than controls after a period of water deprivation. In the present series of studies, a total of 14 male and 2 female naive hooded rats served as Ss. Results show that DSs ate less food than sham operates (SHs), indicating that DSs' body fluids probably do not become as hyperosmotic as those of the SHs. When Ss were maintained on a moist mash during water deprivation, subsequent water intake and air licking were about the same for DSs and SHs. After combined food and water deprivation, both groups air-licked at greatly reduced rates. After subcutaneous injections of hypertonic saline, DSs air-licked just as much as SHs. It is concluded that DSs drink less after water deprivation because they eat less dry food than SHs during deprivation. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Hyperphagia in rats with experimental diabetes mellitus: A response to a decreased supply of utilizable fuels.

In 2 experiments with male Sprague-Dawley rats, alloxan-diabetic rats were hyperphagic when fed diets containing little fat, but they ate normal amounts of food when given diets rich in fat. Normal Ss increased food intake to the same degree when the caloric density of their diet was decreased by reducing the content of fats or carbohydrates in isocaloric amounts. Diabetic Ss did not respond substantially to changes in caloric density of their diet which were produced by altering the content of dietary carbohydrates, but they systematically increased food intake as the amount of fat in their diet was reduced. Diabetic Ss ate normal amounts of a high-fat diet despite continued loss of nutrients in urine and persisting impairments in glucose utilization, fat storage, and liver glycogen deposition. Findings suggest that hyperphagia in experimental diabetes mellitus is a compensatory response to a lack of utilizable fat fuels rather than the result of a metabolic disturbance per se. (33 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Feeding, activity, and body temperature following 6-hydroxydopamine lesions in diabetes (db/db) mice.

Reductions in central catecholamines produced by intraventricular injections of 6-hydroxydopamine (6-OHDA) cause weight loss and decreased plasma glucose in diabetes (db/db) mice. The present study examined the effects of this treatment in short-term (64-day) and long-term (120-day) survival groups of female diabetes (C57 BL/KsJ-db/db) and lean mice. Phenotypically heterozygotes (db/m) and homozygotes (m/m) were used as controls. Diabetes Ss treated with 6-OHDA decreased food intake, lost weight, and maintained a lower weight than vehicle-treated controls until vehicle-treated Ss began to enter the terminal stages of the syndrome, indicated by a loss of body weight. Diabetes Ss given 6-OHDA lost weight despite reduced body temperatures and activity levels. Blood glucose levels were always lower in 6-OHDA than in ad lib fed vehicle-treated db/db Ss. The 6-OHDA treatment also improved pancreatic islet granulation. Pair feeding vehicle-treated with 6-OHDA-treated db/db Ss did not halt weight gain in the vehicle-treated group. However, measurement of carcass fat indicated similar losses in db/db-6-OHDA Ss and vehicle-treated Ss when the vehicle group was pair-fed with lean controls. Treatment with 6-OHDA produced long-term improvement in the diabetes syndrome, but the decreased body weight of the 6-OHDA-treated diabetes Ss could not be completely accounted for by changes in food intake or energy expenditure. (43 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Endocrine interactions in regulation of body weight by female rats.

Studied food intakes and body weights in 65 overweight female Sprague-Dawley rats that were sham-operated, adrenalectomized, or adrenalectomized and ovariectomized. Before surgery the groups were equivalent. Postoperatively, the adrenalectomized Ss showed diminished food consumption and body weight relative to the ovariectomized and adrenalectomized Ss. Data are discussed in terms of a delicate estrogen-progesterone balance in the control of body weight. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Seasonal weight gain is attenuated in food-restricted ground squirrels with lesions of the suprachiasmatic nuclei.

Assessed the role of seasonal hyperphagia in the genesis of prehibernation fattening 19 female golden-mantled ground squirrels (Spermophilus lateralis). Control Ss (n?=?17) were fed ad lib throughout the weight gain phase of the annual bodyweight cycle (June–October), and neurologically intact Ss (n?=?7) and Ss with brain lesions incorporating the suprachiasmatic nuclei (SCN; n?=?5) were fed amounts of food equivalent to quantities consumed prior to the bodyweight trough (May). Results indicate that part of the seasonal increase of body mass was independent of increases in food consumption; intact Ss and controls underwent similar increases in body mass and possessed equivalent amounts of abdominal white adipose tissue. Food restriction combined with SCN lesions attenuated seasonal weight gain and reduced abdominal fat mass. However, some brain-damaged Ss still evidenced weight gain. It is concluded that SCN are involved in circannual body weight rhythm generation, but their contribution to this process is not essential for continued rhythmicity in most individuals. (19 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Comparison of ovarian and hypothalamic obesity syndromes in the female rat: Effects of diet palability on food intake and body weight.

Results of 2 experiments with 96 CFE female rats show that both ovariectomy and hypothalamic knife cuts produced hyperphagia and obesity in Ss. The ovarian obesity, however, unlike hypothalamic obesity, was virtually independent of diet palatability. Ovariectomized Ss became obese on quinine-adulterated diets which completely blocked hypothalamic obesity, and they displayed little further weight gain when given a high-fat diet which greatly potentiated hypothalamic obesity. Ovarian and hypothalamic obesity were also found to be additive irrespective of diet condition when both surgical treatments were combined in the same S; that is, ovariectomy increased the food intake and body weight of knife-cut Ss given the quinine or high-fat diet. In contrast to their dissimilar feeding effects, ovariectomy, hypothalamic cuts, and the combined surgeries did not differentially alter the aversion to a 0.01% quinine solution. Results indicate that ovarian obesity and hypothalamic obesity represent 2 different feeding disorders and are mediated by separate neural mechanisms. The functional nature of these disorders is discussed in light of recent body weight set point interpretations. (40 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Hyperphagia and obesity produced by parasagittal and coronal hypothalamic knife cuts: Further evidence for a longitudinal feeding inhibitory pathway.

Hyperphagia and obesity are produced by parasagittal knife cuts through the medial hypothalamus and by coronal knife cuts through the posterior hypothalamus. Results of the present series of experiments with 91 female CFE rats indicate that the 2 types of cuts produce their overeating effect by severing the same neural pathway. Exp I demonstrated that unilateral parasagittal knife cuts combined with contralateral coronal cuts in either the posterior hypothalamus or the midbrain significantly increased food intake and body weight. Exp II revealed that bilateral parasagittal cuts and bilateral coronal cuts in the hypothalamus produced qualitatively similar effects on food intake, diurnal ingestive pattern, finickiness, and amphetamine anorexia. The 2 types of cuts differentially altered water intake, however. In Exp III, coronal cuts in the posterior hypothalamus, like parasagittal cuts in the medial hypothalamus, increased the food intake and body weight of Ss previously given bilateral parasagittal transections through the lateral perifornical region. The neuroanatomy and neurochemistry of the longitudinal feeding inhibitory pathway suggested by these results are discussed. (31 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Regulation of energy balance in two models of reversible obesity in the rat.

Reports on 2 experiments with 114 adult male Sprague-Dawley rats. Ss were made obese either by tube feeding varying fractions (34, 47, 68, or 75%) of their normal food intake or by offering them a varied and palatable diet (cafeteria diet). After 17–30 days of these regimens, the treatments were withdrawn, and Ss were allowed free access to the normal stock diet. Tube-fed Ss precisely adjusted voluntary food intake to compensate for the energy delivered by tube but nevertheless became obese as a result of an increased metabolic efficiency. Cafeteria-fed Ss were hyperphagic and became obese without any apparent change in metabolic efficiency. Recovery from obesity was more rapid in cafeteria Ss and was due to a pronounced increase in heat production as well as concomitant hypophagia. Ss previously made obese by tube feeding exhibited hypophagia and returned to normal weight without any change in heat production. The relevance of these results to the concept of lipostasis and the relative roles of energy intake and expenditure in the regulation of energy balance are discussed. (17 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)