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T W Castonguay

Publications and source records attributed to T W Castonguay.

17 recordsLinked to original sources

Effect of adrenalectomy and high-fat diet on the fatty Zucker rat.

Lean and obese Zucker fatty rats were adrenalectomized or sham operated at 10 wk of age. At 15 wk one-half of each group was placed on a high-fat diet. At 32 wk of age the experiment was ended. Several conclusions can be drawn about the effects of adrenalectomy, high-fat diets, and their interaction in the Zucker fatty rat. First, adrenalectomy slowed the weight gain in both obese fatty rats and in the lean animals, although the effect was greater in the fatty rats. Second, weight gain was accelerated in intact lean and fatty rats eating a high-fat diet. Third, adrenalectomy attenuated the weight gain associated with a high-fat diet and reduced the body content of fat and protein in the lean animals and fatty rats fed the low-fat diet. Fifth, adrenalectomy significantly affected the retroperitoneal and subcutaneous fat depots but not the epididymal fat depot. Sixth, adrenalectomy decreased fat cell number in retroperitoneal and subcutaneous fat depots, but this was much less evident in the epididymal fat depot. Seventh, lipoprotein lipase activity expressed per milligram protein increased after adrenalectomy in the fatty rat but was reduced on the same basis in lean animals regardless of diet. Finally, the increase in retroperitoneal lipoprotein lipase activity expressed per fat cell observed in lean animals fed the high-fat diet was not observed in the fatty rat. These studies show that a high-fat diet and adrenalectomy interact in the development of obesity in both lean and fatty Zucker rats.

Adipose Tissue

Effects of increasing brain GABA on the meal patterns of genetically obese vs. lean Zucker rats.

To explore recent suggestions that genetically obese Zucker rats show less anorexia when brain gamma-aminobutyric acid (GABA) is elevated, obese vs. lean littermates received 100, 50 and 0 micrograms of the GABA-transaminase inhibitor, ethanolamine-O-sulfate (EOS), intra-cisternally in a longitudinal design where their feeding patterns were monitored 24 h daily. Obese rats were refractory to EOS-induced anorexia as evidenced by less suppression of daily food intake and fewer alterations to both meal size and meal frequency, particularly in the night. This effect was not due to an inability of EOS to increase brain GABA since equivalent, specific dose-dependent increments were seen in the brains of separate obese vs. lean rats after analysis of endogenous GABA and seven other amino acids. An unexpected finding was elevated levels of brain taurine for obese rats regardless of EOS dosage, implying a hitherto unknown neurochemical trait whose potential significance is unclear. The primary data obtained provide further support for recent hypotheses that obese Zucker rats possess altered brain GABAergic mechanisms that may serve as one contributor to their over-eating.

Animals

Effect of chronic insulin administration on food intake and body weight in rats.

Insulin was chronically administered to rats to determine its effect on the daily changes in food intake and body weight. Animals received regular insulin via 14-day osmotic minipumps in doses of 0.0, 0.5, 1.0, 3.0, and 5.0 IU/day treated either with (+GLU) or without glutamic acid (-GLU). Previous studies have shown that glutamic acid prevents insulin aggregation in the minipumps to provide a more stable flow rate. Food intake and body weights were measured each day of treatment. Chronic insulin treatment was ineffective in promoting changes in animals receiving any dose of insulin except the highest dose. Animals receiving 5.0 IU/day insulin + GLU experienced a transient hyperphagia and weight gain followed by a suppression in food intake and body weight by Day 4 of treatment. Effects were attenuated in animals receiving insulin -GLU. Plasma insulin concentrations on Day 14 were similar for all doses, suggesting a compensation took place either in insulin degradation or endogenous insulin production. Results indicate that glutamic acid treatment enhances the effects of chronic insulin administration via osmotic minipumps.

Animals

Dietary fat, hypothalamic glutamate decarboxylase, and food intake of streptozotocin-diabetic rats.

The association among changes in glucose status, glutamate decarboxylase (GAD) activity, and food intake was evaluated in several hypothalamic areas of streptozotocin-diabetic rats fed a low- (12% of calories as fat) or high-fat diet (59% of calories as fat). Control rats consumed approximately 90 kcal/24 h of either diet, whereas diabetic rats consumed approximately 150 kcal/24 h of the low-fat diet and approximately 100 kcal/24 h of the high-fat diet. At the end of the study, diabetic rats fed the high-fat diet weighed more and had higher retroperitoneal fat depot weights (P less than 0.05) than diabetic rats fed the low-fat diet. In diabetic rats, GAD activity was 15-20% higher in the ventromedial nucleus (P less than 0.01) but similar to controls in the lateral hypothalamus, paraventricular nucleus, and area postrema. Diet did not affect GAD activity in the brain areas studied. The increase in ventromedial nucleus GAD activity was not associated with the level of food intake and was the likely result of altered glucose homeostasis in diabetic rats.

Animals

Adrenal modulation of the enhanced fat intake subsequent to fasting.

Elevations in corticosterone have been linked with the enhanced fat appetite of genetically obese Zucker rats. The present study set out to describe the effects of elevations in corticosterone in adult male Sprague-Dawley rats. Previous studies have shown that food deprivation leads to a time-dependent increase in basal corticosterone concentrations. It was predicted that rats would select a high fat diet during initial refeeding subsequent to a 24-hour fast and more severe food deprivation (48 hours) would promote greater fat consumption. Dependence upon adrenal hormones for this enhanced fat intake was examined with adrenalectomized animals. It was hypothesized that adrenalectomy would prevent the increase in fat intake seen in intact animals. Two experiments were performed. In the first, rats were given access to three separate macronutrient sources and allowed to self-select a diet for 7 days. They were then divided into groups and deprived of food for 0, 24, or 48 hours. At the end of the restriction period each rat was tail bled and macronutrient access was restored. Intakes were measured and blood samples taken at 1, 3, 6, 12, and 24 hours following restored access. During the first hour of refeeding, food-deprived animals ate significantly more fat than nondeprived animals. The enhanced fat intake was positively correlated with the elevations in corticosterone observed at the start of the refeeding period (r = .72). In the second experiment, rats were allowed to self-select a diet for 9 days. On Day 10 the rats received either bilateral adrenalectomies or sham operations.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenal Glands

Circadian rhythm of corticosterone in diabetic rats.

We proposed that the circadian rhythm of corticosterone in diabetic rats would have a different pattern than that in non-diabetic control rats. To test this hypothesis, 20 male Sprague-Dawley rats were given ad libitum access to a stock diet and housed individually in a light and temperature controlled room. Ten rats were made diabetic by two subcutaneous injections of streptozotocin. Ten rats which were not injected served as controls. Thirteen days after induction of the diabetes, tail blood samples were taken every 4 h for 24 h. Plasma corticosterone levels were significantly higher in diabetic rats than in control rats at 3 time points during the light cycle; however, concentrations were similar during the dark cycle. We speculate that diabetes may cause alterations in the steroid feedback mechanism to the hypothalamus and/or pituitary, resulting in an abnormal circadian rhythm of plasma corticosterone.

Animals

Aldosterone reverses potassium-induced food aversions in adrenalectomized rats.

Young adult male rats were individually housed and given a standard ration (66 ml) of a liquid diet (Nutrament) each day. The animals were divided into 7 groups: five groups were bilaterally adrenalectomized (ADX) and given one of 5 doses of aldosterone and/or dexamethasone by continuous, osmotic minipump infusions. The remaining two groups served as intact and sham operated controls. Each of the seven groups were subdivided into 3 dietary groups: a basal potassium dietary group, a moderately potassium-supplemented dietary group, and a highly potassium-supplemented dietary group. All rats with intact adrenals as well as those ADX rats given basal or 10 X basal aldosterone treatment consumed all of their allotted 66 ml of diet each day, independent of the level of potassium supplementation. ADX rats given little or no aldosterone treatment that were given access to the moderately or highly supplemented diets became anorexic, eating little or none of the diet. These data are discussed with reference to the factors controlling the intake of ADX rats.

Adrenal Glands

Capsaicin and its effects upon meal patterns, and glucagon and epinephrine suppression of food intake.

The neurotoxin capsaicin has been shown to selectively interfere with unmyelinated sensory fibers, as well as leading to depletions of substance P and other peptides. Meal pattern analysis was performed both before and after treatment with capsaicin in twelve adult male Sprague-Dawley rats. Capsaicin treatment only briefly altered feeding patterns. No long term effect on body weight was noted. These same animals were then tested for the appetite suppressing effects of IP injections of glucagon (125 micrograms/kg) and epinephrine (30 micrograms/kg). Capsaicin treated rats decreased their intake of sweetened condensed milk during a 30 minute test in response to glucagon and epinephrine. Controls failed to suppress intake in response to glucagon, but drank less milk after epinephrine than did capsaicin treated rats. Efficacy of capsaicin treatment was obtained using similarly treated animals subject to histological evaluation within 2 days of capsaicin treatment. These results suggest that peripherally generated information relayed to the CNS via small-diameter sensory neurons is not a necessary component of the normal hunger/satiety sequence, nor body weight regulation.

Animals

Meal patterns of rats with dorsomedial hypothalamic nuclei lesions or sham operations.

Rats with bilateral dorsomedial hypothalamic electrolytic lesions (DMNL rats) are hypophagic, hypodipsic and have reduced linear and ponderal growth when compared to sham operated controls (SCON). Nevertheless, previous studies have shown that DMNL rats eat and drink adequate amounts for their size and have normal body composition. In the present study we investigated meal parameters: meal size, and frequency (both light and dark period), total intake and meal size per metabolic size (body weight 0.75). Compared to SCON, DMNL rats at twelve days post surgery weighed less, were shorter, but had a normal body composition as determined by the Lee Index, and were hypophagic (grams eaten/day). The animals were placed into individual, self-contained feeding modules and given powdered chow. After familiarization to the modules, meal parameters were recorded continuously by a computer for an eight day period. While dark phase meal frequency did not differ significantly between groups, the lesioned rats took more meals during the light period. Over the eight-day measurement period DMNL rats were hypophagic compared to SCON in absolute terms. However, when total intake and meal size were normalized to metabolic size, these two parameters did not differ significantly between groups. Upon refeeding, after a one-day fast, the initial meal size of the normally hypophagic DMNL rats exceeded that of SCON. Rats with DMNL have previously been shown to have deficits in some hypothesized short-term food intake control mechanism (e.g., cholecystokinin, glucose sensing). Thus overeating by the lesioned rats after a fast could possibly result from a specific short term control deficit.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals

Age, sex and reproductive status alter the severity of anorexia in zinc deficient rats.

Food intake and body weight gain in rats fed a zinc-deficient diet are reported. The severity of zinc deficiency-induced anorexia was observed to be dependent upon the age, sex and reproductive status of the animal. Rapidly growing rats such as weanlings, adult males, or ovariectomized females demonstrated more rapid induction of anorexia and more severe effects on cumulative food intake and body weight gain when fed zinc-deficient diets than did slowly growing (nonpregnant female adult) rats given the same diet. These results suggest that feeding in zinc-deficient animals is not regulated by dietary zinc concentration alone, but rather is mediated by one or several as yet undefined factors.

Age Factors

Meal pattern analysis: artifacts, assumptions and implications.

The meal patterns of 12 male Sprague-Dawley rats were monitored continuously for eight consecutive days. During that time, food intake was measured every second, accurate to 0.01 gram. Results from this procedure demonstrated that the correlation between meal size and meal duration was, at best, weak. Further, the correlation between meal size and either the pre or post meal interval was also weak (approximately 0.20). Subsequent re-evaluation of the patterns using different end-of-the-meal criteria resulted in a significant interaction between the end-of-the-meal definition and the strength of the correlation between meal size and post meal interval, with more robust correlations being observed with the use of longer end-of-the-meal definitions. In an attempt to resolve the question of which definition to use, log survivorship analysis was applied to the interval data. Results from that procedure suggest that a 10 minute end-of-the-meal definition is appropriate in most cases in the analysis of daytime patterns, and a 5 minute definition should be used when quantifying nighttime patterns. Under these "data determined" conditions, the correlation between meal size and post meal interval was not statistically significant. The implications of these results with respect to a homeostatic model of feeding behavior are discussed.

Animals

Some metabolic and behavioral effects of adrenalectomy on obese Zucker rats.

Ten-week-old female obese and lean Zucker rats were given access to three separate macronutrient sources (casein, starch, and lard) for 7 days. They were then either adrenalectomized (ADX) or given a sham operation. Rats were assigned to one of three groups and given a daily injection of either 0, 2, or 10 mg of corticosterone. They continued to select a diet for another 17 days, after which they were killed, and their blood was assayed for corticosterone, adrenocorticotropin hormone (ACTH), insulin, glucose, and triglyceride. Retroperitoneal and parametrial fat depots were excised and sampled for lipoprotein lipase activity, fat cell size, and number. Body composition was also determined. Selection patterns of lean and obese rats were markedly affected by both ADX and corticosterone replacement. All three groups of sham-operated obese rats ate significantly more fat than did sham-operated lean rats. Adrenalectomy significantly reduced fat intakes in both obese and lean rats. Corticosterone therapy restored fat appetites of lean and obese rats in a dose-dependent fashion. In comparison to ADX lean rats, ADX obese rats reduced their normally elevated levels of blood glucose, plasma triglycerides, and insulin to within normal limits. Similarly, adipose cellularity of the ADX obese rats was reduced to that of sham-operated lean rats. Carcass fat was significantly reduced after adrenalectomy. Corticosterone therapy prevented the reduction in a dose-dependent way.

Adipose Tissue

Flavor, forced choice and deprivation affect corticosterone selection by the adrenalectomized rat.

Adrenalectomized rats were given access to corticosterone-supplemented (20 micrograms/ml) and -unsupplemented saline (0.9% NaCl) in two separate bottles and preferences were measured for each. Half of the rats received corticosterone in maple-flavored saline (MAPLE group), while the other half received corticosterone in anise-flavored saline (ANISE group). Each rat also received unsupplemented saline in the alternate flavor. After an initial preference test, preferences were measured again following a period of forced choice (where rats were given the supplemented saline only) and again following a period of deprivation (where rats were given the unsupplemented saline only). All three independent variables (flavor, forced-choice and deprivation) played roles in determining self-administration of corticosterone. Results from the initial preference test demonstrated that both groups preferred the maple-flavored saline whether it contained corticosterone or not. However, consumption of corticosterone-supplemented saline regardless of flavor increased following both forced-choice and deprivation suggesting that the adrenalectomized rats were controlling their corticosterone levels. Strong negative correlations were found between intake of corticosterone-supplemented saline and body weight suggesting that the adrenalectomized rat may be controlling corticosterone levels based on some correlate of body weight.

Adrenal Glands

Nutritional influences on dietary selection patterns of obese and lean Zucker rats.

Little is known about the behavioral, nutritional, and metabolic events that control dietary intake quality. Two experiments are described that manipulate nutritional conditions that have been hypothesized to affect dietary item choice so as to assess what effect, if any, the added factor of genetic obesity has in modifying the response to these manipulations. In the first experiment, 5 week old male obese and lean Zucker rats were fed a diet that varied in protein content (10%, 20%, or 60% casein by weight) for ten weeks. They were then allowed to select a diet from three separate macronutrient sources (casein, starch, or corn oil). Although body weights at the end of the 10 week maintenance period were markedly different, selection patterns were not influenced by pre-feeding different levels of protein. Obese rats selected a diet that was higher in fat and lower in protein than the diets composed by lean rats. In the second experiment, four groups of 7 month old obese and lean Zucker rats were given access to one of four diets that varied in protein content (5%, 10%, 15%, or 20% casein by weight). In addition, each rat was periodically given access to a 32% sucrose solution. Access to sucrose promoted increases in total caloric intake, independent of the protein content of the diet. Obese rats typically ate more calories per day than did their lean littermates. Results from these experiments suggest that food item selection is determined more by factors associated with obesity than by factors associated with dietary history.

Animal Nutritional Physiological Phenomena

Effect of adrenalectomy and corticosterone replacement on meal patterns of Zucker rats.

Male obese and lean Zucker rats were adrenalectomized (ADX) or sham-operated at 10 wk of age. Approximately 16 wk later, patterns of food intake were monitored by computer-interfaced top loading balances. Data were collected from ADX rats before, during, and after access to a corticosterone-supplemented saline solution (20 micrograms/ml). Although total food intake during the precorticosterone treatment period was not different between ADX and sham controls, ADX resulted in attenuation of light cycle food intake, primarily via decreased meal frequency. With steroid replacement, light cycle meal frequency and food intake increased. Despite comparable self-administered dose (20.33 +/- 0.89 vs. 17.05 +/- 1.2 mg corticosterone/period, obese vs. lean), obese ADX rats were more responsive to steroid than were lean ADX rats. This increased responsiveness was reflected by a 30% increase in food intake and 60% increase in body weight gain of obese ADX rats during replacement. Lean ADX rats exhibited no change in total food intake or weight gain with replacement. Further, during corticosterone treatment, obese ADX rats increased meal frequency, total food intake, and consumption of large meals (greater than or equal to 4 g) during the dark cycle. Significant postprandial correlations were found only in obese ADX rats, both with and without replacement during the dark cycle. These results suggest adrenal glucocorticoids have a minimal effect on food intake and meal patterns in lean Zucker rats but significantly alter intake and meal patterns in obese rats.

Adrenalectomy

Glucocorticoids as modulators in the control of feeding.

Three sets of experiments have been conducted that suggest that adrenal glucocorticoids play a role in the long-term control of intake and in dietary preferences. First, obesity is dependent upon glucocorticoid-modulated metabolic pathways. Surgical or pharmacological manipulations in obese animals that eliminate or diminish corticosterone activity result in levels of intake, meal patterns, macronutrient self-selection and weight gain that revert to levels seen in lean controls. Glucocorticoid replacement of adrenalectomized genetically obese Zucker rats restores the phenotypic expression of the obese rat's genetic heritage: increased weight gain, increased fat and total daily caloric intake and adiposity are restored in a dose-dependent fashion. Second, the increased fat intake observed subsequent to fasting in Sprague-Dawley rats is correlated with an increase in circulating corticosterone. Adrenalectomy blocks the fat specific refeeding response, and corticosterone treatment of adrenalectomized rats restores the increase in fat, carbohydrate and protein observed during refeeding. Third, humans suffering from Cushing's Disease have an increased preference for dietary fat. Weight-matched but disease-free obese controls show only slight increases in fat preference when compared to normal weight controls.

Animal Feed

A reexamination of the effects of intracerebroventricular glucocorticoids in adrenalectomized rats.

Several investigators have reported that many of the behavioral and metabolic effects of ADX can be reversed by appropriate levels of glucocorticoids administered either peripherally or centrally. The present studies were conducted to offer a comparison of the effects of orally administered corticosterone (CORT) with ICV glucocorticoids [CORT, CORT acetate, or dexamethasone (DEX)]. Of particular interest were the effects of glucocorticoid treatment on body weight gain and on macronutrient self-selection. Adult male Sprague-Dawley rats were fitted with ICV cannulae and either bilaterally ADX or given sham operations. In the first experiment, ADX animals were initially treated systematically with CORT (20 micrograms/ml in their drinking water). After a wash-out period during which no steroids were administered, ADX rats were given daily ICV CORT injections (100 micrograms/day in 10 microliters). Systemic CORT treatment promotes weight gain and normal food choice patterns in ADX rats. ICV injections failed to promote weight gain in ADX rats, and daily injection of the vehicle promoted a weight loss in sham-operated controls. Four additional experiments were conducted. ADX, glucocorticoid-treated animals and ADX, vehicle-treated controls as well as sham-operated, vehicle-treated controls were used to assess the effects of both steroid and vehicle on body weight gain and dietary selection patterns. ADX ICV-glucocorticoid-treated animals typically failed to gain weight at the rate observed when ADX rats are treated with CORT systematically. Under one condition, ADX-CORT-treated animals gained weight at a rate comparable to untreated controls, but their ICV-injected control group failed to gain weight.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenalectomy