Biomedical subjects

D B West

Publications and source records attributed to D B West.

53 records · Page 3Linked to original sources

PubMed1992

The effects of gonadectomy on glucose tolerance of genetically obese (fa/fa) rats: influence of sex and genetic background.

In both humans and rodents the occurrence and severity of obesity-associated non-insulin dependent diabetes mellitus (NIDDM) may be influenced by both gonadal hormones and genetic background. Early gonadectomy (at 3-5 days of age) of female and male Wistar diabetic fatty (WDF) rats and of male Zucker rats allowed us to examine these effects in genetically obese rats carrying the fatty (fa) gene. Impairment of glucose tolerance and insulin sensitivity by obesity, and amelioration or exacerbation (in the case of female rats) of this impairment by gonadectomy were assessed by intragastric glucose tolerance tests when the rats reached adulthood. Both glucose tolerance and insulin sensitivity were significantly deranged in obese WDF rats of both sexes and in obese male Zucker rats compared to lean controls of the same sex and strain. Obese male WDF rats were less glucose tolerant and insulin sensitive than were obese male Zucker rats. Glucose intolerance was not ameliorated by castration in lean or obese male WDF or Zucker rats. Insulin sensitivity was significantly improved by castration in obese male rats of both strains, as fasting plasma insulin levels and total areas under the insulin curves were significantly reduced compared to obese sham-operated controls. This effect was greater in the Zucker than in the WDF male rats. Castration significantly decreased the insulin response areas in obese male Zucker rats, but did not alter those of the obese male WDF rats. Ovariectomy did not alter glucose homeostasis of obese female WDF rats.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1990

Baroreflex sensitivity in the canine model of obesity-induced hypertension.

Studies have demonstrated abnormalities in baroreflex function in various models of hypertension. The purpose of this study was to examine baroreflex sensitivity in the canine model of obesity-induced hypertension. Baroreflex sensitivity was determined by the relative changes in heart rate (HR) in response to changes in mean arterial pressure (MAP) induced by sodium nitroprusside (Nitro) and phenylephrine (Pe). Studies were performed in conscious lean dogs (n = 10) and obese dogs fed a high-fat diet for 6 wk (n = 8). Body weight averaged 18.1 +/- 0.3 kg in the lean dogs and 26.5 +/- 0.5 kg in the obese dogs. Associated with the 46% increase in body weight in the obese dog group were significant increases in MAP (120.7 +/- 3.0 vs. 102.8 +/- 1.5 mmHg) and HR (132.7 +/- 8.5 vs. 96.4 +/- 3.3 beats/min). Administration of Nitro (0.5, 1.0, 5.0 micrograms.kg-1.min-1) resulted in comparable reductions in MAP in the lean and obese dogs. The reflex increases in HR were significantly greater in the obese animals only with a dose of 5.0 micrograms.kg-1.min-1 of Nitro (55.5 +/- 7.7 vs. 32.0 +/- 7.5 beats/min). Administration of Pe (0.5, 1.0, 5.0 micrograms.kg-1.min-1) resulted in significantly greater increases in MAP in the obese dogs (17.8 +/- 4.6 vs. 4.9 +/- 2.6, 37.1 +/- 4.4 vs. 19.6 +/- 2.7, and 72.7 +/- 7.5 vs. 51.5 +/- 7.1 mmHg).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1989

Regional changes in adipose tissue blood flow and metabolism in rats after a meal.

Adipose tissue blood flow was measured in five depots, and plasma concentrations of glucose, insulin, and triglyceride were measured at 0, 15, 30, and 45 min after the start of a meal in unanesthetized, freely moving rats. In addition, adipose tissue lipoprotein lipase activity was measured in four depots before and 45 min after the start of a meal. Plasma glucose was significantly elevated only at the 15-min time point, and while plasma triglyceride increased these changes did not reach significance. Plasma insulin was significantly elevated at all time points after a meal. Feeding resulted in a consistent decrease of adipose tissue blood flow expressed per gram wet weight of tissue. This decrease was maximal at 30 min after the start of feeding. The decrease in adipose tissue blood flow averaged 45% at 45 min after the start of feeding for the five depots evaluated. Lipoprotein lipase activity significantly increased in the retroperitoneal and mesenteric fat depots at 45 min after the meal start, but did not change in the epididymal or dorsal subcutaneous fat depots. These results suggest that a decrease in adipose tissue blood flow is a normal result of a meal in the rat. The regional specificity of changes in adipose tissue lipoprotein lipase activity supports the concept of regional specificity of function for adipose tissue and suggests that the mesenteric and retroperitoneal depots are particularly important for the storage of triglycerides immediately after a meal.

Adipose Tissue↗

PubMed1989

Sexual dimorphism of hyperglycemia and glucose tolerance in Wistar fatty rats.

Obese and lean male and female Wistar fatty rats were fed a high-sucrose (68% of calories) diet from 5 to 22 wk of age. Obese males, but not obese females, developed hyperglycemia in the fed state and were more glucose intolerant during an intragastric glucose tolerance test than obese females. Lean Wistar fatty rats did not become hyperglycemic on the sucrose diet. Obese males also showed a smaller insulin response during the glucose tolerance test than did obese females. The Wistar fatty rat is a sexually dimorphic model of non-insulin-dependent diabetes mellitus in which the male but not the female obese rats become diabetic. The diabetic condition and impaired glucose tolerance in the obese male Wistar fatty rat may be related to impaired pancreatic insulin release and peripheral insulin resistance.

Aging↗

PubMed1988

Lipogenic potential in liver of the preweanling rat: influence of dietary cholesterol.

We examined the effect of a lower dietary cholesterol load on hepatic lipogenic capacity and plasma cholesterol concentrations during the normal suckling period in artificially reared preweanling rats. The artificially reared rats were fed a milk formula that contained low or normal concentrations of cholesterol during the period from the 5th to 17th day after birth. The activities of HMG-CoA synthase and HMG-CoA reductase in livers of 17-day-old rat pups reared on the low-cholesterol diet were enhanced three- to five-fold over those observed in the age-matched rats in the normal cholesterol and mother-reared control groups. The concentration of cholesterol in plasma of rats reared on the low-cholesterol milk was about 20% lower than that for mother-reared controls. In contrast, rats reared on milk with normal cholesterol content exhibited plasma cholesterol levels about 25 and 50% higher than the mother-reared and low cholesterol groups, respectively. The long-term metabolic consequences of rearing rats on milk formulations without adequate cholesterol remains to be determined.

Animals↗

PubMed1987

Infusion of cholecystokinin between meals into free-feeding rats fails to prolong the intermeal interval.

The sulfated octapeptide of cholecystokinin (CCK-8) was infused intraperitoneally into 7 free-feeding male Sprague Dawley rats over a 6-day period. Infusions were given near the end of each free-feeding meal (1.87 microgram/meal/rat), and also during the intermeal interval in gradually increasing doses (0.10-0.63 microgram/5 min/rat). Food intake was continuously monitored and the infusions were controlled by microcomputer. Meal patterns, total food intake, and body weights during drug infusion were compared with data collected during a baseline period when only saline was infused. Meal-contingent CCK-8 infusion produced a significant 29.9% decrease in meal size which persisted throughout the drug-infusion period. Intermeal infusion of CCK-8 failed to prolong the intermeal interval (IMI) but it did initially prevent the compensatory decrease in IMI and increased feeding frequency expected after meal size was reduced. By the last day of drug infusion, total daily food intake recovered to baseline levels due to increased feeding frequency. Body weight was only transiently reduced by CCK-8 infusion. These findings show that tolerance does not develop to the action of CCK-8 to suppress meal size, and the administration of exogenous CCK-8 to free-feeding rats does not persistently prolong the intermeal interval.

Animals↗

PubMed1987

Lithium chloride, cholecystokinin and meal patterns: evidence that cholecystokinin suppresses meal size in rats without causing malaise.

Gut hormones which are proposed as natural satiety factors may act through malaise to suppress short-term feeding instead of through a normal physiological process. Evaluation of the ability of candidate satiety hormones to serve as the unconditioned stimulus in the development of a conditioned taste aversion is not adequate evidence of malaise since agents which do not produce malaise in humans are also capable of conditioning aversions. Examination of the patterns of eating behavior when drugs are given during a meal in rats may serve as a better test of the potential of an agent to produce illness. To evaluate this approach, LiCl (a known aversive agent) was infused into five rats at the start of each free-feeding meal at a dose of 1.9 mg/meal/rat for four days and at 3.8 mg/meal/rat for an additional four days. Feeding patterns during drug infusion were compared with patterns for six days when no drugs were infused. LiCl infusion produced a significant dose-dependent reduction in feeding frequency while the size and duration of meals were not changed. At the higher dose of lithium, daily meal number was reduced from a normal 13.2 +/- 1.4 to 9.9 +/- 0.5 meals/day. This pattern of behavior is significantly different from the behavior exhibited when cholecystokinin octapeptide (CCK-8) was infused using the same paradigm. CCK-8 significantly reduced meal size while meal frequency increased to compensate for the smaller meals. These findings suggest that LiCl infusion during a meal will lead to an aversion to feeding while CCK-8 is not effective at producing an aversion.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1987

Long-term effects on adiposity after preweaning nutritional manipulations in the gastrostomy-reared rat.

Male Long-Evans rat pups were either fed by continuous intragastric infusion of a milk formula to match the growth rate of their normally reared siblings, or overfed by continuous infusion of a fat-supplemented formula from d 4 through d 18 postpartum. The early overfeeding accelerated growth and the overfed rats remained significantly heavier than normally reared siblings as adults. Early overfeeding with this procedure led to an adult obesity at 14 mo characterized by significantly larger epididymal and retroperitoneal fat depots resulting from an increase of both fat cell size and number, and by an increase in adipose tissue lipoprotein lipase activity. Gastrostomy rearing per se, without overfeeding, resulted in adult rats that weighed the same as normally reared siblings but had significantly larger retroperitoneal fat depots because of more adipocytes. These findings suggest that the quantity of food consumed during early growth and development, and the quality of early nutrition and/or the early rearing environment affect adipose tissue development and have long-term consequences that persist in the rat.

Animal Nutritional Physiological Phenomena↗

PubMed1987

Adipocyte blood flow is decreased in obese Zucker rats.

Blood flow to five adipose tissue depots and five other organs was measured in unanesthetized free-moving obese and lean male Zucker rats using the radiolabeled microsphere technique. Cardiac output and blood pressure were also measured. Obese rats were significantly heavier and had larger fat depots characterized by more and larger adipocytes. Cardiac output and blood pressure were similar in lean and obese rats. Blood flow to adipose tissue was substantially reduced in all five depots of obese rats when expressed per square millimeter of cell surface. When blood flow was expressed per cell, it was reduced in obese rats in the dorsal subcutaneous and inguinal depots and significantly elevated in the obese mesenteric adipose depot. Significant interdepot differences in blood flow were observed in both lean and obese rats. Nonadipose organ blood flow was not different between obese and lean rats, but when expressed on a per gram basis, blood flow through triceps surae muscle, epididymis, and testis was elevated in obese rats. These findings suggest that there is a substantial alteration of hemodynamics in obesity that may contribute to or reflect the altered metabolism of adipose tissue in obese rats. Furthermore, interdepot differences of adipose tissue blood flow also parallel reported interdepot differences in metabolism.

Adipose Tissue↗

PubMed1986

Intraventricular insulin reduces food intake and body weight of lean but not obese Zucker rats.

Porcine insulin (2 mU/rat/day) and its saline vehicle were infused into the third cerebral ventricle of female lean or obese Zucker rats using 14-day osmotic minipumps. Lean rats receiving saline (N = 6) gained 14 +/- 3 g over the 14 days, whereas lean rats receiving insulin (N = 7) lost 12 +/- 4 g over the same interval (p less than 0.01). The average total food intake of the insulin-infused group was decreased by 14% (p less than 0.05) as compared with that of the saline-infused group. The decreased caloric consumption was adequate to account for the body weight loss. Insulin infusion had no effect on food intake or body weight of the obese rats relative to their saline-infused controls (change in body weight: saline (N = 5), -14 +/- 23 g; insulin (N = 7), +3 +/- 14 g). These results suggest that genetically obese Zucker rats have reduced sensitivity to insulin in the central nervous system. We propose that this phenomenon may participate in the development and maintenance of hyperphagia and obesity in these animals.

Animals↗

PubMed1984

Cholecystokinin persistently suppresses meal size but not food intake in free-feeding rats.

Food and water intake of free-feeding rats with indwelling intraperitoneal catheters connected to infusion pumps was continuously monitored and recorded by a microcomputer-based data acquisition system. Initially, at the start of every spontaneous meal for 4 days, each rat was infused with 0.27 ml of physiological saline. Saline infusion did not affect any feeding or drinking patterns, and the rate of weight gain remained unchanged. For 6 subsequent days, the octapeptide of cholecystokinin (CCK-8, 1.1 micrograms/meal) dissolved in physiological saline was infused at the onset of each meal. CCK-8 infusion caused a dramatic shift of patterns of food intake. Average meal size was reduced by at least 44%, whereas daily meal number increased by 162% or more for all 6 days of CCK-8 infusion. Total daily food intake recovered to predrug levels by the 4th day of CCK-8 infusion, primarily due to increased feeding frequency. Average body weight dropped by 12.4 g on the 1st day of CCK infusion, but over the following 5 days the growth rate was not different from the base-line predrug rate. With discontinuation of CCK-8 infusion all meal patterns returned rapidly to normal and body weight immediately recovered.

Animals↗

PubMed1983

A microcomputer-based data acquisition system for continuous recording of feeding and drinking by rats.

A monitoring system to continuously record the daily pattern of drinking and eating of rats is described. This system, based on a North Star microcomputer, can record the amount of food ingested with a temporal resolution of +/- 1.0 second and quantitative accuracy within +/- 5%. Drinking behavior is detected using a drinkometer which also has a temporal resolution of +/- 1.0 second. Data are analyzed by computer to determine absolute amounts of consumption and patterns of intake. The patterns of feeding and drinking recorded by this system are similar to those observed using other monitoring devices.

Animals↗

PubMed1983

Immunocytochemical detection of insulin in rat hypothalamus and its possible uptake from cerebrospinal fluid.

Insulin-like immunoreactivity (IRI) was detected in the rat hypothalamus, particularly in the paraventricular, periventricular, supraoptic, suprachiasmatic, arcuate, and lateral hypothalamic nuclei. The immunostainable IRI was diffusely distributed in comparison to the neuronal concentrations of immunostainable vasopressin in the periventricular nucleus, or of IRI in islet B cells, suggesting that immunostainable IRI in the hypothalamus is not concentrated in neuronal perikarya. To determine if insulin in cerebrospinal fluid (CSF) may be a source of some insulin in brain tissue, [125I]iodoinsulin was stereotaxically injected into a lateral cerebral ventricle, and the uptake of radioactivity into periventricular hypothalamus was localized by both quantitative autoradiography of paraffin-embedded brain sections and by measuring the radioactivity present in microdissected brain regions. In brains that received lateral ventricular injections of labeled insulin, the concentration of radioactivity in the periventricular region of the hypothalamus, as revealed by autoradiographic grains, was significantly greater than that in the periventricular region of brains that received lateral ventricular injections of labeled insulin mixed with an equimolar excess of an unlabeled peptide (insulin, ribonuclease, or both together). The highest levels of radioactivity detected in both autoradiographic and microdissection procedures were in regions nearest to the third ventricle, suggesting that insulin in the lateral ventricles has access to the periventricular neuropile in the hypothalamus. The staining pattern of immunostainable insulin in the hypothalamus along with the distribution of radioactivity after CSF injection of labeled insulin are consistent with the hypothesis that insulin is taken up into brain from the CSF.

Animals↗

PubMed1982

Infant gastrostomy and chronic formula infusion as a technique to overfeed and accelerate weight gain of neonatal rats.

Female rat pups were overfed by continuous intragastric infusion of a milk formula from day 4 through day 128 postpartum. These rats dramatically accelerated weight gain after day 109. By day 18 the overfed pups weighted significantly more than both normally reared 18-day-old pups and pups reared artificially but maintained at the same growth rate as normally reared pups. On day 18 the catheters were removed from gastrostomized pups and normally reared pups were removed from their dams. Thereafter, all groups were maintained ad libitum on a standard diet. The body weights of overfed pups were still significantly greater than those of both other groups on day 120. The procedure provides an important new tool to examine the role of early nutrition in the etiology of obesity.

Animals↗

PubMed1981

Peptides and the control of meal size.

There are now a large number of experiments demonstrating that peripheral administration of exogenous cholecystokinin or its synthetic analogue, CCK-8, reduces meal size in a number of species. The peptide interacts with other factors which influence satiety, and treatments thought to be effective in eliciting secretion of cholecystokinin have predictable effects on meal size. Cholecystokinin is effective in the genetically obese Zucker rat, obese rats with lesions of the ventromedial hypothalamus, and subdiaphragmatically vagotomized rats. Somatostatin and bombesin are also reasonable candidates for satiety factors. Intraperitoneal naloxone reduces meal size in rats, and beta-endorphin injected intraventricularly causes an increase in meal size of 50% over 30 minutes. We conclude that cholecystokinin and bombesin may interact in weight regulation and control of meal time food intake.

Appetite↗

PubMed1980

Ventromedial hypothalamic lesions increase pancreatic sensitivity to streptozotocin in rats.

Rats with electroytic lesions of the ventromedial hypothalamus (VMX rats) and sham-operated controls (SHAM rats) were injected with streptozotocin (STZ) at a dose of 50 mg/kg 48 h after the lesions were made. VMX rats were significantly more sensitive to STZ in that over 70% died within 6 wk, shereas none of the SHAM rats dies. When smaller doses of STZ were given to VMX rats (30--35 mg/kg), a large percentage still died, although the survivors appeared equally as diabetic (in terms of hyperglycemia and hypoinsulinemia) as SHAM rats given a larger dose of STZ. At 25 mg/kg, the surviving VMX rats were more hyperglycemic than matched controls. We suggest that the increased B-cell activity known to occur in VMX animals might be the important factor in the increased sensitivity to STZ observed. We speculate that similar variation in pancreatic B-cell response to an environmental injury may be an important determinant of diabetes susceptibility in man.

Animals↗

PubMedDate not supplied

Bombesin reduces food intake of normal and hypothalamically obese rats and lowers body weight when given chronically.

Bombesin is a peptide hormone reported to reduce meal size when administered in rats. In the first experiment, synthetic bombesin was injected subcutaneously into normal rats and obese rats with lesions of the ventromedial hypothalamus just prior to the presentation of food. A dose-dependent suppression of meal size occurred for both groups, showing that the peptide has this action in obese as well as normal animals. In a second experiment, a conditioned taste aversion was not formed with a dose of bombesin which suppressed meal size by approximately 50% while the animals did develop an aversion with a dose of LiCl reported to reduce meal size equivalently. In a third experiment, rats were placed on a feeding schedule where they received three 30-min meals each day. After weights had stabilized under this paradigm, bombesin was administered just prior to each meal for six days. The bombesin caused a consistent suppression of meal size when the animals were allowed 30-min meals such that the rats lost weight over the six-day period. When this experiment was repeated with 60-min meals apparent tolerance developed to these actions of bombesin.

Animals↗