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Biomedical subjects

J S Stern

Publications and source records attributed to J S Stern.

At least 145 records · Page 8Linked to original sources

Exercise termination effects on food intake, plasma insulin, and adipose lipoprotein lipase activity in the Osborne-Mendel rat.

Thirteen-week-old male, Osborne-Mendel rats were exercised for 6 weeks on a motorized treadmill. Exercise depressed weight gain and cumulative light cycle food intake while cumulative dark cycle and 24-hour total food intake were unaffected. Rats in sedentary and exercise groups were killed 24 hours after the last bout of exercise to assess the effects of chronic exercise and at 48, 60, 72, and 84 hours to determine the effects of exercise termination. Compared to sedentary controls, exercise decreased plasma insulin, epididymal and retroperitoneal depot weight and cell size, and retroperitoneal lipoprotein lipase (LPL) activity. Forty-eight hours after exercise, plasma insulin concentration increased to sedentary levels. By 60 hours, dark cycle food intake was increased above and adipose LPL activity was comparable to sedentary levels. At 84 hours postexercise termination, dark cycle food intake, plasma triglyceride, and epididymal LPL activity per depot and per cell were significantly greater than sedentary values. Exercise termination resulted in a preparatory response for rapid lipid deposition probably arising from increased food intake, plasma insulin, and enhanced LPL activity within 84 hours following termination of exercise.

Adaptation, Physiological↗

Dietary magnesium intake influences exercise capacity and hematologic parameters in rats.

The effects of feeding varying concentrations of dietary Mg (50, 100, 200, or 400 ppm) for 22 days on exercise capacity and hematologic parameters were investigated in male rats. Five-week-old male Osborne-Mendel rats fed diets containing 50 or 100 ppm Mg developed transitory priapism and hyperemia, signs of Mg deficiency. Based on a treadmill test, these rats showed a markedly lower exercise endurance capacity (four hours) than rats fed the higher levels of dietary Mg (six hours). They also showed a mild macrocytic anemia. Consumption of a mineral water containing 85 ppm Mg prevented these signs of Mg deficiency. These results show that a reduction in exercise capacity can be an early effect of Mg deficiency. Hematologic changes that occurred with Mg deficiency such as macrocytic anemia may be responsible, at least in part, for the depression of exercise observed in these rats. These data are important because they illustrate the potential significance of even a marginal deprivation of dietary magnesium.

Animals↗

Weight gain and food intake in corticotropin releasing factor immunized Zucker rats.

In Zucker obese rats (fa/fa) there are disturbances in the regulation of ACTH and corticosterone. In addition, beta-endorphin concentrations are higher in the pituitary and hypothalamus in obese than in lean rats. Since ACTH and beta-endorphin are thought to be controlled by corticotropin releasing factor (CRF), these effects may be due to abnormalities in CRF regulation. This possibility was investigated by immunizing rats against CRF. Obese rats immunized against CRF developed higher titer antibodies than lean rats. Hypothalamic CRF concentrations were higher in CRF-immunized obese but not lean rats compared with those of control rats, suggesting that compensation for sequestration of peripheral CRF developed in obese rats. In obese, but not lean rats, immunization against CRF decreased weight gains during weeks 1-4 and increased gains during weeks 9-12 and food intakes were decreased during weeks 5-8 compared with those for obese rats immunized against bovine serum albumin (BSA). Adrenal glands weighed 30% less in both obese and lean rats immunized against CRF compared with those immunized against BSA. These responses to immunization against CRF occurred even though plasma, hypothalamic and pituitary concentrations of ACTH and beta-endorphin were unaffected at the end of the study.

Adrenocorticotropic Hormone↗

Cold-induced metabolism and brown fat GDP binding in young and old rats.

The attenuated thermogenic responses observed in older animals exposed to low environmental temperatures may reflect decreased thermogenic capacity of brown adipose tissue, a major nonshivering thermogenic effector in rats, and/or decreased metabolic capacity of lean body mass. To evaluate these possibilities, the oxygen consumption of female Sprague-Dawley rats aged 5 and 26 months was recorded at rest and during 6 h of exposure to 6 degrees C. The thermogenic capacity of brown fat was estimated from the binding of guanosine-5'-diphosphate (GDP) to isolated brown fat mitochondria. Both resting and cold-induced oxygen consumption expressed on a mass independent basis [ml/(min x kg body mass.67)] and as a function of lean body mass [ml/(min x g lean body mass)] were significantly lower in the 26-month-old animals. Colonic temperatures of younger and older rats after the 6 h of cold exposure were 37.5 +/- 0.1 and 36.1 +/- 0.2 degrees C, respectively, and were significantly different. However, no significant differences in the binding of GDP to isolated brown fat mitochondria were observed. These data indicate that the thermogenic capacity of brown fat is not decreased in the aged rat, and that the metabolic capacity as well as the amount of lean body mass is altered with age.

Adipose Tissue, Brown↗

Cold-induced increase in brown fat thyroxine 5'-monodeiodinase is attenuated in Zucker obese rat.

In this study we examined the possibility that the reduced brown adipose tissue (BAT) thermogenesis in the Zucker obese rat may result from a limited capacity for enzymic conversion of thyroxine (T4) to triiodothyronine (T3) in BAT. A total of 34 lean and obese rats, approximately 4 mo old were divided into three treatment groups: group 1 (5 lean and 6 obese) was fed Purina rat chow for 21 days, and group 2 (5 lean and 6 obese) was fed a cafeteria diet for 21 days, and group 3 (6 lean and 6 obese) was fed Purina rat chow and maintained in the cold (8 +/- 1 degrees C) for 7 days. The lean and obese rats in all three groups of animals were matched closely for age and respective body weight. Activity of T4 5'-deiodinase was determined as the rate of T3 production from added T4 under controlled in vitro conditions. Serum T4 and T3 were determined by radioimmunoassay. The rate of T4-to-T3 conversion in BAT was similar in the lean and obese rats maintained at room temperature, whether fed rat chow or a cafeteria diet (approximately 40-50 pmol T3/scapular BAT depot per h). However, expressed per scapular BAT depot, lean rats exposed to cold displayed about a fivefold increase in BAT T3 production (P less than 0.0001), whereas only a small increase was observed in the cold-exposed obese rats. Serum T3 levels tended to be reduced in the Zucker obese rats. Our data indicate a reduced capacity for T3 production in Zucker rat BAT exposed to cold.(ABSTRACT TRUNCATED AT 250 WORDS)

Acclimatization↗

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↗

Hyperprolactinemia stimulates food intake in the female rat.

Lactation in the rat is marked by extreme hyperphagia. The present study examined the possibility that elevated prolactin levels contribute to this increase. It also evaluated the effects of hyperprolactinemia on brown adipose tissue and carcass composition. Virgin Osborne-Mendel rats were made hyperprolactinemic via ectopic pituitary transplants (PIT, n = 9) or were sham-operated (SHAM, n = 8). Eight lactating rats (LACT) served as additional controls. Food intake, body weight and rectal temperature were recorded daily. Eleven days postsurgery (or 11-12 days postpartum), the rats were sacrificed, and brown fat (scapular, axillary, cervical and thoracic) was excised, weighed, and assayed for GDP binding, one indicator of thermogenic capacity. Carcasses were subjected to body composition analysis. Although prior to surgery, PIT and SHAM rats weighed the same, PIT rats gained significantly more weight during the experiment than did SHAMs. Percent body fat and food intake (both total intake and intake relative to metabolic body size) were significantly elevated in the PIT rats. GDP binding in both PIT and LACT rats was significantly less than in SHAMs. This was true whether GDP binding was expressed per mg mitochondrial protein or per total amount of mitochondrial protein recovered. These data confirm that brown fat thermogenic capacity is suppressed during lactation. They also demonstrate that elevations of serum prolactin, to levels that are well within physiological limits, are capable of stimulating food intake and white fat deposition in the female rat. It is presently unclear whether these results are a direct or an indirect effect of hyperprolactinemia.

Adipose Tissue, Brown↗

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↗

Effect of adrenalectomy on in vivo glucose metabolism in insulin resistant Zucker obese rats.

Lean (Fa/?) and obese (fa/fa) Zucker rats were adrenalectomized (ADX) in order to assess the contribution of adrenal hormones to insulin resistance of the obese Zucker rat. Glucose utilization was measured using an insulin suppression test. Sham-operated obese rats gained almost twice as much weight as sham-operated lean littermates. However, body weight gain of ADX animals was comparable in both genotypes. It was significantly less than that of the respective sham-operated controls. Body weight differences can be accounted for almost entirely by a marked loss of adipose tissue. Although insulin resistance may be attributable to obesity in part, steroid hormones are thought to be directly antagonistic to insulin for glucose metabolism. Adrenalectomy resulted in a decrease in serum glucose concentrations for both lean and obese Zucker rats compared with their respective sham-operated groups. Serum insulin concentration of lean ADX rats was 23% of sham-operated controls; in obese ADX rats, it was 9% of controls. Elevated levels of steady state serum glucose (SSSG) levels in sham-operated obese rats demonstrate a marked resistance to insulin induced glucose uptake compared with sham-operated lean animals. Adrenalectomy caused a marked improvement in insulin sensitivity of obese rats. The hyperglycemic SSSG levels of the obese rats were reduced 2.5 times by ADX. These results indicate that insulin resistance of Zucker obese rats can be ameliorated by ADX, suggesting adrenal hormones contribute to insulin resistance in these animals.

Adrenal Cortex Hormones↗

Energy expenditure in rats with diet-induced obesity.

Effects of a diet high in fat on body weight, adiposity, and energy expenditure were investigated. Male rats were fed 8% (control) or 50% fat (by weight) for 6 mo. The high-fat group increased body weight (+26%), adipocyte size (+61%), and adipocyte number (+48%). However, food intake and resting oxygen consumption, although higher in absolute amount, were normal in that both were commensurate with the greater body mass the rats maintained. When body weight and adipocyte size were reduced by caloric restriction, the high-fat group displayed the same adaptive adjustments in resting oxygen consumption as controls. We conclude that rats fed high-fat diets for prolonged periods 1) have energy intakes and expenditures appropriate for the greater tissue mass and adipocyte number they maintain, and 2) show adaptive reductions in energy expenditure when food is restricted, which provide further evidence that the regulated level of body weight can be altered by such diets.

Adipose Tissue↗

Metabolism at thermoneutrality and in the cold is reduced in the neonatal preobese Zucker fatty (fa/fa) rat.

Minimum and maximum rates of oxygen consumption (VO2) were determined in 2-, 6- and 8-d-old lean (Fa/?) and preobese (fa/fa or "fatty") Zucker rats. On each study day, three or four naive littermate male pups were placed in individual respiration chambers submerged in a water bath and studied simultaneously over a range of ambient temperatures (24-35 degrees C). The purpose of the cold exposure was to elicit maximal oxygen consumption and to determine the ability of the rat to maintain body temperature during cold stress. Minimum rates of oxygen consumption were observed at 33-34 degrees C in both groups. As ambient temperature was reduced, VO2 increased and rectal temperature decreased. Regression analysis revealed a significantly reduced oxygen consumption in the preobese pups within the thermoneutral zone and during cold exposure. A defect in energy expenditure for heat production was evident in the preobese (fa/fa) pups as indicated by their attenuated cold-induced rate of oxygen consumption and decreased ability to maintain body temperature during cold stress relative to their lean (Fa/?) littermates. Their lower VO2 within the thermoneutral zone implies that the preobese (fa/fa) pups have a decreased metabolic rate even under conditions in which cold-induced thermogenic mechanisms are turned off.

Adipose Tissue, Brown↗

Effect of adrenalectomy and glucocorticoid replacement on development of obesity.

Female obese and lean Zucker rats were adrenalectomized (ADX) or sham-operated at 4 wk of age. ADX animals were given daily injections of 0.01, 0.05, 0.50, 1.0, or 2.0 mg hydrocortisone/100 g body wt for 30 days. ADX rats gained less weight than sham-operated controls. Obese ADX rats at the lowest dose (0.01) had a net positive energy gain but lost body fat. As steroid dose increased, obese rats deposited more fat and less protein. Doses of 0.01 and 0.05 mg produced rats that were less fat than sham-operated controls, whereas doses of 0.50, 1.0, and 2.0 mg produced rats of comparable body fat composition. Obese rats were consistently fatter and had a significantly smaller percentage body protein than lean rats at each dose. Body fat elevation was reflected by heavier parametrial and retroperitoneal fat depots and larger fat cells at all doses except the lowest. Compared with sham-operated controls, lean and obese rats at the two lowest replacement doses (0.01, 0.05) exhibited significantly decreased plasma insulin and triglyceride levels and significantly elevated brown adipose tissue protein content and citrate synthase (CS) activity. Obese rats at these doses had significantly reduced adipose tissue lipoprotein lipase (LPL) activity in the retroperitoneal depot and lower food intake. Furthermore, these obese rats had adipose depot weights, cell sizes, LPL activity, and plasma insulin, glucose, and triglyceride comparable to that of lean sham-operated controls. As steroid dose increased (0.5, 1.0, 2.0), plasma insulin and triglyceride and food intake markedly increased only in obese rats. Adipose tissue LPL activity appeared unaffected by dose. Brown adipose tissue protein content and CS activity significantly decreased as dose increased in both lean and obese rats. At all doses of replacement obese rats were more responsive to steroid than were lean rats. Obese rats receiving 0.01 mg had comparable fat depot weights, cell sizes, and plasma insulin and triglyceride as lean rats receiving 50 times as much steroid per day (0.50 mg). These results suggest glucocorticoids play an important role in the early development of obesity in the Zucker rat and support the hypothesis that obese rats are more responsive to glucocorticoids than are lean rats.

Adipose Tissue↗

Brown fat mediates increased energy expenditure of cold-exposed overfed neonatal rats.

Genetically lean rat pups, overfed by being raised in small litters of three from day 1 postpartum, rapidly become obese compared with pups raised in standard sized litters of eight. Because of the rapid onset of their obesity, we expected that overfed pups would exhibit defective brown fat thermogenesis as is seen in neonatal genetically obese rodents. O2 consumption (VO2) was measured in 2-, 4-, 6-, and 8-day-old homozygous lean (Fa/Fa) Zucker pups from each treatment. We determined minimum rate of VO2 at thermoneutrality and maximum VO2 in response to progressively colder ambient temperatures. Overfed pups were fatter than standard-fed pups (P less than 0.001). But contrary to our prediction, overfed pups had a significantly increased maximum VO2 in response to acute cold exposure. To test the hypothesis that brown fat mediated the increased VO2 in the overfed pups, scapular brown fat lipectomies were performed on a new group of overfed pups at 2 days of age and compared with sham-operated littermate controls. On day 8, no differences in minimum VO2 were seen at thermoneutrality when brown fat is turned off. But maximum VO2 in response to cold, when brown fat is turned on maximally, was significantly reduced in the lipectomized overfed pups compared with sham-operated overfed littermates. These data suggest that manipulations of diet, accomplished by raising pups in small litters, can increase brown fat thermogenic function. The results of the lipectomy experiment imply that brown adipose tissue is a primary mediator of the increased energy expenditure in response to acute cold exposure in the overfed pups.

3-Hydroxyacyl CoA Dehydrogenases↗

Blood flow to brown fat in lean and obese adrenalectomized Zucker rats.

The Zucker obese rat is characterized by decreased capacity for diet-induced and for nonshivering thermogenesis. This decrease is due, in large part, to reduced thermogenesis in depots of brown adipose tissue, a major source of heat production in rats. Adrenalectomy retards the weight gain observed in the obese rats and also normalizes brown fat guanosine 5'-diphosphate (GDP) binding, an in vitro measure of brown fat thermogenic capacity. This study examined the effect of adrenalectomy on brown fat blood flow, an in vivo measure of the tissue's function, and on norepinephrine-induced O2 consumption (NST) of 11-wk-old obese (fa/fa) and lean (Fa/?) rats. Adrenalectomy had little effect on weight gain, NST, or norepinephrine-stimulated blood flow to brown fat in lean rats. However, adrenalectomy produced profound changes in the obese animals, preventing the weight gain normally occurring in the obese rats and normalizing both NST capacity and norepinephrine-stimulated blood flow to brown fat. These findings provide further support for the importance of brown fat thermogenesis and glucocorticoids in modulating the obesity of the Zucker rat.

Adipose Tissue, Brown↗

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↗

Comparison of percutaneous endoscopic gastrostomy with surgical gastrostomy at a community hospital.

The results of percutaneous endoscopic gastrostomies in 100 patients in a community hospital were compared with those of surgically placed gastrostomies in 50 patients. The morbidity rate for the percutaneous endoscopic gastrostomy group was 4%, compared with 30% for the patients with surgically placed gastrostomies. The procedure-related mortality for percutaneous endoscopic gastrostomy was 1%, compared with 16% for surgically placed gastrostomies. Patients admitted to the hospital for percutaneous endoscopic gastrostomy stayed an average of 4 days compared with 10 days for the surgical patients; 14 patients had the percutaneous endoscopic gastrostomy performed as an outpatient procedure. There were no complications in this group, suggesting that percutaneous endoscopic gastrostomy can be safely performed as an outpatient. In this community hospital, percutaneous endoscopic gastrostomy was both substantially safer and far less expensive than surgically placed gastrostomy.

Aged↗

Dynamics of insulin hypersecretion by obese Zucker rats.

The relationship between obesity and hypersecretion of insulin by the pancreas was studied. We found that pancreata from obese Zucker rats secrete significantly more insulin than do pancreata from lean Zucker rats. At a glucose stimulation of 300 mg/dL, the overall dynamic biphasic insulin secretory profiles from obese and lean rats were similar. Further studies to investigate the glucose-insulin dose response relationship in obese and lean rat pancreata demonstrated insulin hypersecretion by pancreata from obese rats which was particularly pronounced at normoglycemic and hypoglycemic levels (by factors as much as 14-fold). This hypersecretion is so striking as to suggest that in the intact state the obese animal may lack the ability to readily "shut off" its insulin secretion under normoglycemic conditions, whereas lean animals possess such an ability. Under hypoglycemic conditions (75 mg/dL), the hypersecretion is transient and insulin secretion returns to normal basal levels after 30 minutes of perfusion. Thus the degree to which this hypersecretory phenomenon may occur in vivo remains to be established.

Animals↗

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↗