Biomedical subjects

T W Castonguay

Publications and source records attributed to T W Castonguay.

At least 19 recordsLinked to original sources

PubMed2001

Effects of adrenalectomy and hormone replacement on B6C3F1 mice fed a high-fat diet.

Bilateral adrenalectomy (ADX) causes decreased circulating leptin in both obese and lean mice. It remains unclear whether the decreased plasma leptin after ADX is due to decreased adipose tissue or is due to decreased circulating glucocorticoids. The present experiment was performed to test the hypothesis that the absence of glucocorticoids from circulation is sufficient to decrease circulating leptin. Sixty-four adult male B6C3F1 mice were individually housed and fed either Purina rat chow or an experimental diet. After 6 weeks, mice fed the experimental diet gained more weight than mice fed the control diet. Each dietary group was then subdivided into four groups: ADX with cholesterol replacement (ADX-CHOL), ADX with corticosterone (CORT) replacement (ADX+CORT), ADX with aldosterone (ALDO) replacement (ADX+ALDO), and sham operation (SHAM). Two days after surgery, mice were killed and exsanguinated and the carcasses were prepared for gravimetric analyses. Blood was collected and centrifuged and the plasma was assayed for leptin, CORT, and ALDO. Blood glucose was determined using whole blood taken before centrifugation. There was no difference in body weight due to ADX after 2 days. Mice fed the experimental diet had higher circulating leptin than those fed the control diet. The ADX+CORT groups (both experimental and control diets) had higher plasma leptin concentrations than the other groups. No differences were observed between ADX-CHOL and SHAM groups. These results suggest that circulating leptin is not directly controlled by glucocorticoids. The effect of ADX on circulating leptin reported by others may be the consequence of decreased adiposity.

Adrenal Cortex Hormones↗

PubMed1999

Adrenalectomy reduces adiposity by decreasing food efficiency, not direct effects on white adipose tissue.

OBJECTIVE: This study was conducted to establish the effects of adrenalectomy (ADX) on adipose tissue metabolism in male Sprague-Dawley rats fed a standard chow diet. RESEARCH METHODS AND PROCEDURES: The effects of adrenalectomy on adipose cell size, lipoprotein lipase activity, and basal and insulin-stimulated glucose conversion to lipid and lipolysis were measured. RESULTS: ADX decreased body weight gain during the post-operative period in the absence of changes in food intake; feed efficiency was decreased significantly. ADX decreased adipocyte size by 30%. ADX increased adipocyte response to the effect of submaximal concentrations of insulin on lipid synthesis and lipolysis. ADX decreased maximally insulin-stimulated lipid synthesis, but this effect was accounted for by decreased adipocyte size. In contrast, ADX had no effect on maximally insulin-inhibited lipolysis. ADX did not affect heparin-releasable LPL. The small effect of ADX on residual extractable adipose tissue LPL activity was accounted for by decreased fat cell size. DISCUSSION: ADX decreased adiposity in the absence of changes in food intake, lipoprotein lipase activity, and adipocyte lipid metabolism. The effect is best attributed to decreased feed efficiency.

Adipocytes↗

PubMed1999

Elevated leptin concentrations in pregnancy and lactation: possible role as a modulator of substrate utilization.

Energy needs are increased during pregnancy and lactation. These increased energy needs may be met through partitioning of nutrients for energy utilization which is under hormonal control. The objective of the present studies was to determine if changes in plasma leptin occurred during pregnancy and lactation and if the changes were related to prolactin. Plasma leptin and prolactin were measured longitudinally in 9 women through pregnancy and lactation. In a second study, leptin and prolactin were measured 4 days and 28 days postpartum in 21 lactating women. Mean plasma leptin during the three trimesters of pregnancy was significantly higher (29.3+/-2.8 ng/ml) when compared to mean leptin during the three time periods of lactation (19.3+/-3.2 ng/ml) and control groups (9.8+/-1.4 ng/ml). Plasma leptin was elevated early in pregnancy and remained elevated throughout pregnancy. In the second study, the mean plasma leptin in the lactating women was significantly higher 4 days postpartum (17.3+/-3.7 ng/ml) and 28 days postpartum (19.2+/-3.9 ng/ml) when compared to controls (11.6+/-1.2 ng/ml). Prolactin in the control subjects (24+/-4 ng/ml) was significantly lower than in the pregnant (202+/-16 ng/ml) and lactating (108+/-26 ng/ml) groups. Similar observations were made in the second study (controls 20+/-2 ng/ml; lactation 28 days 159+/-21 ng/ml). Leptin during lactation was lower than in pregnancy but higher than control subjects. Regression analysis suggested that BMI and prolactin can be used as predictors of leptin in pregnancy and lactation. The increase in leptin and prolactin early in pregnancy suggests an association between the two hormones. Results of the present studies and research done by other investigators presents a strong role for leptin during pregnancy and lactation. Leptin is regulated by factors other than adiposity especially in reproductive women leading to our hypothesis that there are leptin and prolactin mediated effects on substrates used for energy utilization during pregnancy and lactation.

Adolescent↗

PubMed1999

Decreased responsiveness to dietary fat in Otsuka Long-Evans Tokushima fatty rats lacking CCK-A receptors.

Adult Otsuka Long-Evans Tokushima fatty (OLETF) rats lack functional cholecystokinin A (CCK-A) receptors, are diabetic, hyperphagic, and obese, and have patterns of ingestion consistent with a satiety deficit secondary to CCK insensitivity. Because dietary fat potently stimulates CCK release, we examined how dietary fat modulates feeding in adult male OLETF rats and their lean [Long-Evans Tokushima (LETO)] controls. High-fat feeding produced sustained overconsumption of high-fat diet (30% corn oil in powdered chow) over a 3-wk period in OLETF but not LETO rats. We then assessed the ability of gastric gavage (5 ml, 1-2 kcal/ml x 15 s) or duodenal preloads (1 kcal/ml, 0.44 ml/min x 10 min) of liquid carbohydrate (glucose), protein (peptone), or fat (Intralipid) to suppress subsequent 30-min 12.5% glucose intake in both strains. In OLETF rats, gastric and duodenal fat preloads were significantly less effective in suppressing subsequent intake than were equicaloric peptone or glucose. These results demonstrate that OLETF rats fail to compensate for fat calories and suggest that their hyperphagia and obesity may stem from a reduced ability to process nutrient-elicited gastrointestinal satiety signals.

Animals↗

PubMed1995

An evaluation of the use of total body electrical conductivity for the estimation of body composition in adult rats: effect of dietary obesity and adrenalectomy.

Total body electrical conductance (TOBEC) has been recommended for serial measurements of body composition in animals and humans. This study examined the accuracy of the TOBEC technique in predicting body composition of a population of adult male rats that had undergone seven different treatments, including adrenalectomy and blocking of glucocorticoid receptors, in the study of the etiology of obesity. The predicted body composition values of the animals (n = 57, body weight 550 +/- 8 g) obtained by using the manufacturer's and Baer's equations were compared to the actual body composition obtained by direct carcass analysis. Both equations underestimated lean body mass and reciprocally overestimated body fat (manufacturer's 103 +/- 4 g, Baer's 55 +/- 3 g). A new prediction equation was developed based on the conductivity index and the actual lean body mass. This revised equation was able to accurately estimate the lean body mass of the animals used in the same experiment but over-estimated lean body mass of larger animals (n = 10, wt. 647 +/- 13 g). Conclusions based on multiple comparisons (Duncan's) of predicted and actual values resulted in different effects of treatments on body composition. To improve accuracy and reliability of the TOBEC technique, a prediction equation should be developed from the same population as the studied population, and experimental group sizes used for examining treatment effects should be relatively large.

Adipose Tissue↗

PubMed1995

Comparison of effects of adrenalectomy and RU-486 in rats given a choice of maintenance diet and fat supplement.

The effects of adrenalectomy (ADX) and the blockade of glucocorticoid receptors by RU-486 on Sprague-Dawley rats given a choice of a maintenance diet and a fat supplement were studied. Adult male rats were given free access to AIN-76A diet only (CON) or AIN-76A diet and a separate dietary fat option for 4 wk (FAT). They were then assigned to one of the following treatments: ADX, sham operation, ADX with corticosterone (CORT) replacement, RU-486 injections, or vehicle injections. Food intake and body weight were monitored daily for an additional 3 wk. ADX decreased caloric intake and weight gain in the FAT group more than in the CON group. RU-486 also decreased caloric and fat option intakes as well as weight gain. ADX, but not RU-486, reduced body fat content, lowered plasma insulin and triglyceride levels, and decreased glucose intolerance. CORT replacement partially prevented the effects of ADX on weight gain and body fat content. The results of this study indicate that ADX has greater effects on weight gain and body fat accumulation than does RU-486.

Adrenalectomy↗

PubMed1994

Hormone and somatic changes in rats pair-fed to growth retarded dorsomedial hypothalamic nuclei-lesioned rats.

Rats with dorsomedial hypothalamic nuclei lesions (DMNL) are hypophagic and have reduced linear and ponderal growth, but have normal body composition and anabolic hormone concentrations. Previous studies have shown rats pair-fed to levels consumed (70-80% of ad lib) by DMNL rats, using a meal-feeding paradigm, have abnormal body composition and hormone concentrations. Whether the noted changes were due to restriction per se or method of food presentation was uncertain. In the present study, one group of sham-operated rats was pair fed (SHPF) by a computer-operated system that presented 45 mg food pellets in the exact amount and pattern as their DMNL yoked partner; another sham-operated group was ad lib fed (SHAD). At the end of Experiment 1 (11 days) and Experiment 2 (3 weeks) blood was collected for hormone and metabolite analyses; body compositions were also determined. Unlike an earlier report, the DMNL and SHPF groups had normal percentage body fat. Percentage carcass protein was similar in all groups at 11 days, but slightly elevated in DMNL rats at 3 weeks. Also, in contrast to an earlier study, plasma-free fatty acid levels were comparable in DMNL and SHPF rats. Plasma insulin was normal in the DMNL and SHPF rats at 11 days, but was lowered (p < 0.05) in the SHPF group at 3 weeks. Plasma thyroxine was reduced (p < 0.01) in the SHPF group at 11 days but returned to normal by 3 weeks. Thyroxine and triiodothyronine levels were normal in the DMNL groups. Plasma corticosterone levels were similar in all groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1994

Corticosterone-responsive and -unresponsive metabolic characteristics of adrenalectomized rats.

Glucocorticoids are important in influencing substrate flux through the metabolic pathways. This study was designed to answer the question "Does adrenalectomy (ADX) cause a shift toward fat metabolism as measured by a decrease in respiratory quotient (RQ)?" Male Sprague-Dawley rats were divided into four groups, ADX, ADX + 20% corticosterone (Cort) (ADX-20%), ADX + 40% Cort (ADX-40%), or sham-operated controls (Sham). ADX-20% received 50 mg and ADX-40% 100 mg Cort dissolved in 250-mg cholesterol pellets and placed subcutaneously. Each rat was monitored for 90 min four times both during a preoperative period and again after a 1-wk postsurgical recovery period in an indirect calorimeter. Cort prevented ADX-induced suppression of weight gain and food intake. ADX decreased motoric activity in both the light and dark periods. Cort restored activity to Sham levels. ADX decreased RQ only in the dark (0.858 ADX vs. 0.891 Sham) and was reversed only in the ADX-40% group. Energy expenditure (EE) was depressed in both the light and dark by ADX; Cort partially restored EE to Sham values in the light period.

Adrenalectomy↗

PubMed1993

The effects of the acute administration of RU 486 on dietary fat preference in fasted lean and obese men.

The effects of RU 486, a potent glucocorticoid antagonist, on dietary fat preference were explored in obese men and lean controls in a double-blind crossover study. An oral 10 mg/kg dose of RU 486 or placebo was administered at midnight the second night of a 48-h hospital stay. Macronutrient and caloric intakes were calculated each day and a taste test of six commercial dairy products (fat content by weight < 0.5%, 2.0%, 3.3%, 10.5%, 18%, and 36%) was performed. Dairy products were judged for pleasantness, creaminess, and overall preference. Subjects were then asked to consume their favorite dairy product until sated. Urinary free cortisol (UFC) and plasma adrenocorticotropic hormone (ACTH), cortisol, insulin, and glucose were determined. Intake of a self-selected diet was recorded. As expected, in response to RU 486, UFC increased from 120 +/- 25 micrograms/24 h to 297 +/- 73 micrograms/24 h (p < 0.05) in obese men and from 81 +/- 10 micrograms/24 h to 357 +/- 109 micrograms/24 h (p < 0.05) in lean men. Plasma cortisol increased from 26.1 +/- 1.1 microgram/dl to 31.8 +/- 1.0 microgram/dl (p < 0.05) in obese men and from 26.1 +/- 1.7 micrograms/dl to 32.2 +/- 1.7 micrograms/dl (p < 0.05) in lean men. Plasma insulin was significantly higher in obese 24.6 +/- 3.2 microIU/ml than in lean men 12.8 +/- 1.1 microIU/ml (p = 0.0001) but was unaffected by RU 486. RU 486 did not decrease fat intake in either obese or lean men.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenocorticotropic Hormone↗

PubMed1993

The effects of chronic cold exposure on diurnal corticosterone and aldosterone rhythms in Sprague-Dawley rats.

Plasma corticosterone (CORT) and aldosterone (ALDO) exhibit diurnal rhythmicity. Cold exposure increases basal plasma CORT and ALDO levels. This study investigated the effects of cold exposure on CORT and ALDO diurnal rhythms. Twelve male Sprague-Dawley rats were housed at 23 degrees C, adapted to a 12:12 day:night cycle (lights on 0900 h), and provided chow and water ad lib. On day 7, 100 microliters tail blood samples were obtained every 4 h for 24 h beginning at 0900 h. The temperature of the animal room was lowered to 4 degrees C. On days 7 and 14 of cold exposure, blood samples were obtained every 4 h as above. After 7 days at 4 degrees C, CORT levels were elevated at 0900 h, 1300 h, and 0500 h (p < 0.05) as compared to levels observed at 23 degrees C. Peak CORT levels were observed at 2100 h in each 24-h sampling session with mean levels of 181.3 +/- 23.3 ng/ml at 23 degrees C, and 200.5 +/- 16.4 ng/ml and 188.1 +/- 19.9 ng/ml after 7 and 14 days at 4 degrees C. In contrast, ALDO levels were elevated at all time points across the day:night cycle after 7 days at 4 degrees C. After 14 days, ALDO levels were elevated at 0900 h, 1300 h, and 2100 h (p < 0.05) as compared to levels observed at 23 degrees C.(ABSTRACT TRUNCATED AT 250 WORDS)

Acclimatization↗

PubMed1993

Aldosterone diurnal rhythm in the rat: a question of cross-reactivity?

Radioimmunoassay (RIA) of plasma aldosterone (ALDO) can be hampered by cross-reactivity with plasma corticosterone (CORT). The purpose of this study was to determine and adjust for CORT crossreactivity when assaying for ALDO in blood samples taken throughout a 24-h period. Plasma was obtained from 10 adrenalectomized male Sprague-Dawley rats. Corticosterone-free plasma was spiked with 0, 50, 75, 100, 150, 200, and 300 ng/ml CORT. Aldosterone determination was performed by RIA. An equation for ALDO concentration adjusted for plasma CORT concentration was calculated (ALDO = measurable ALDO - 0.377 x CORT - 5.324). Twenty male Sprague-Dawley rats were adapted to a 12/12 light/dark cycle (lights on at 0900 h). They were divided into two groups based on body weight. Blood samples were obtained every 4 h beginning at 0900 h from rats in group 1 and beginning at 1100 h from rats in group 2. Distinct diurnal CORT and ALDO rhythms were observed. Corticosterone levels were highest at 2100 h (131.8 +/- 17.8 ng/ml) and lowest at 1300 h (04.6 +/- 1.8 ng/ml). Aldosterone levels were highest at 1900 h (276.50 +/- 53.60 pg/ml) and lowest at 1500 h (27.53 +/- 6.84 pg/ml). Corticosterone and ALDO levels were often significantly correlated (r > 0.60), but not at times when CORT and ALDO levels were at their highest. These results suggest that ALDO and CORT may be regulated by different mechanisms or may have a regulatory influence upon each other throughout the day/night cycle.

Aldosterone↗

PubMed1993

Corticosterone modulation of dietary selection patterns.

Effects of corticosterone (CORT) supplementation on ad lib macronutrient selection and selection following food deprivation were examined in male adrenalectomized (ADX) Sprague-Dawley rats. The ADX rats self-administered CORT from drinking solutions of 0 microgram/ml, 20 micrograms/ml, or 40 micrograms/ml. Adrenalectomy attenuated weight gain, which CORT failed to completely restore. After 6 days, rats were deprived for 0 or 24 h. Adrenalectomy attenuated weight loss during deprivation; CORT failed to restore weight loss. Adrenalectomy reduced ad lib protein intake, which CORT failed to restore. Carbohydrate and fat intakes were not affected by ADX; CORT (40 micrograms/ml) increased fat intake. During the first hour of refeeding, ADX attenuated protein intake; CORT failed to restore intake. Corticosterone-supplemented rats consumed more fat than unsupplemented ADX rats. Over 24 h, unsupplemented, deprived ADX rats consumed less fat and calories than all other deprived groups. These results suggest that CORT affects weight gain in lean rats and modulates macronutrient selection both ad lib and following food deprivation.

Adrenalectomy↗

PubMed1993

Macronutrient choice following food deprivation: effect of dietary fat dilution.

Under standard laboratory conditions rats given access to three separate macronutrient sources compose a diet yielding 31% of their total daily calories as protein, 34% as carbohydrate, and 34% as fat. This selection pattern is dramatically altered with restored access following a 48 h fast. During the first hour of refeeding, rats composed a diet that was low in protein and high in carbohydrates and fat. By the end of 24 h, no difference in selection pattern was found, though intake of all three macronutrients was higher than baseline. A separate group given access to three macronutrient sources of equal caloric density specifically increased fat intake during the period of restored access. Another group, familiarized with a concentrated fat source, was given access to a diluted fat source during refeeding. Similarly, a fourth group, familiarized with a diluted fat source during the baseline condition was given access to a concentrated fat source during refeeding. Results from these experiments suggest that prior experience with a diluted fat source promotes a significant increase in fat intake and a suppression of carbohydrate intake during initial refeeding following a 48 h fast. In a second experiment, rats that were given a choice of both fat sources preferred the concentrated source; 72% of all fat (g) and 82% of all fat calories were consumed from the concentrated fat source. These results suggest that fat intake increases following deprivation not solely due to its inherent relatively increased caloric density but also possibly due to its role in energy metabolism.

Animals↗

PubMed1993

Characterization of suppression of food intake following acute colon inflammation in the rat.

Experimental colitis was induced in rats by intrarectal infusion of trinitrobenzenesulfonic acid and ethanol. Colitis was accompanied by a large suppression of food intake of 3 days duration. The reduction of food intake was effected through a reduction of meal size, with no change in meal frequency. Those same rats demonstrating approximately 70%-80% suppression of daily food intake showed no reduction of sham feeding. These data indicate that malaise alone is inadequate to explain the suppression of food intake associated with acute colitis. Rather, the data suggest that the suppression of eating results from an exaggerated postprandial satiety signal elaborated during the period of acute inflammation, an interpretation consistent with the demonstration of a slowed rate of gastric emptying in association with the colitis.

Analysis of Variance↗

PubMed1992

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↗

PubMed1992

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↗

PubMed1991

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↗

PubMed1991

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↗