Biomedical subjects

J S Stern

Publications and source records attributed to J S Stern.

At least 127 records · Page 7Linked to original sources

PubMed1989

Direct effect of CNS on insulin hypersecretion in obese Zucker rats: involvement of vagus nerve.

It is hypothesized that the vagus nerve makes a major contribution to pancreatic insulin hypersecretion in the genetically obese rat (fa/fa) via direct pancreatic innervation. An in situ brain-pancreas perfusion model with intact pancreatic central nervous system (CNS) innervation was used in these studies. The dynamics of insulin secretion in response to a 40-min glucose stimulus (200 mg/dl) was investigated in CNS intact (INT), bilateral cervical vagotomized (VGX), and CNS functionally ablated (ABL) 11- to 12-wk-old homozygous lean (Fa/Fa) and obese (fa/fa) female Zucker rats. The overall pattern of insulin secretory dynamics from obese and lean rats was similar. However, insulin released during the entire 40-min perfusion period by pancreata from obese rats was significantly greater than in lean rats. In lean rats, there was no significant difference in insulin secretion from pancreata of CNS-INT, VGX, and ABL rats. In obese rats, CNS-INT pancreata secreted almost twice as much insulin as pancreata from obese ABL rats and four times as much insulin as CNS-INT lean rats. This demonstrates that hypersecretion of insulin in obese Zucker rats is comprised of a significant direct CNS component. Although vagotomy had little effect on CNS-INT lean rats, it reversed the CNS component of hypersecretion present in CNS-INT obese rats. Because insulin secretion in CNS-INT obese rats was lowered by vagotomy to that equivalent to values of CNS-ABL obese rats, this demonstrates a significant contribution by the parasympathetic nervous system to the hyperinsulinemia seen in the Zucker obese rat that is attributed to direct parasympathetic innervation of the pancreas.

Animals↗

PubMed1989

Prolactin stimulates food intake in a dose-dependent manner.

Lactation in the rat is marked by pronounced hyperphagia and suppression of brown fat (BAT) thermogenic capacity. We previously examined the possibility that elevated prolactin levels mediate these changes. The present study evaluated the effect of varying prolactin levels on food intake, BAT mitochondrial GDP binding, and carcass adiposity. Female rats were injected daily for 10 days with ovine prolactin at one of three doses: high = 3.0, medium = 1.0, or low = 0.3 micrograms/g body wt. Controls were injected with 0.9% NaCl. A group of uninjected rats served as an additional control. Cumulative food intake was significantly elevated in a dose-dependent manner in the prolactin-treated animals relative to the saline-injected and uninjected controls. Compared with the saline controls, the mean cumulative food intake was greatest at the high dose (20% increase), intermediate at the medium dose (17%), and smallest at the low dose (12%). Prolactin-treated rats gained significantly more weight during the experiment than did controls. Despite the hyperphagia in the prolactin-treated rats, no significant differences in BAT mitochondrial GDP binding were observed among the five groups. These data indicate that elevated prolactin levels stimulate food intake in a dose-dependent manner and that this hyperphagia is not accompanied by an increase in BAT mitochondrial GDP binding.

Adipose Tissue↗

PubMed1989

Prolactin stimulates food intake in the absence of ovarian progesterone.

Increases in serum estrogen inhibit food intake. Conversely, progesterone stimulates food intake, probably via its antiestrogenic action. We have reported that elevated serum prolactin also stimulates food intake in female rats. It is unclear whether this effect is mediated through elevated levels of progesterone. The present study investigated the effects of prolactin on food intake and brown fat activity in the absence of progesterone. Female Osborne-Mendel rats were assigned to one of six groups: sham operated (Sham, n = 10), ovariectomized (OVX, n = 10), OVX + low estrogen (EL, n = 11), OVX + EL + prolactin (PIT, n = 9), OVX + high estrogen (EH, n = 10), and OVX + EH + PIT (n = 8). Estrogen levels were elevated by Silastic implants. Prolactin levels were elevated through pituitary transplants placed under the kidney capsule. Nine days postsurgery, food intake was significantly higher in OVX vs. Sham rats. Estrogen-treated rats (OVX + EL and OVX + EH) had significantly suppressed food intake values compared with both Sham and OVX animals. Finally, hyperprolactinemic rats (OVX + EL + PIT and OVX + EH + PIT) ate significantly more food than did estrogen-treated rats without pituitary explants. Despite the hyperphagia, no significant differences in brown fat GDP binding were observed. These data indicate that prolactin stimulates food intake in the absence of ovarian progesterone.

Adipose Tissue, Brown↗

PubMed1989

Regional blood flow of exercise-trained younger and older cold-exposed rats.

O2 consumption (thermogenesis) and regional blood flows (measured using radioactively labeled microspheres) were evaluated in younger (12 mo) and older (24 mo) sedentary and exercised male Fischer 344 (F-344) rats. These variables were measured at rest and during exposure to 6 degrees C. Exercise-trained rats were run on a motor-driven treadmill 5 days/wk, 1 h/day, at 20 m/min for 6 mo. Resting rates of O2 consumption did not differ with age or exercise training. However, thermogenesis during cold exposure was significantly greater in the older exercised rats than in the other three groups. This difference did not reflect a greater contribution from brown fat as indicated by the fact that total blood flow to the brown fat depots during cold exposure was not greater in the older exercised vs. the other rat groups. Neither exercise training nor age had a significant effect on specific resting blood flow (expressed as ml.min-1.g tissue mass-1) to most of the organs measured, including heart, kidney, brown fat, white fat, and skeletal muscle. The notable exception to this was in the spleen of the older sedentary animals where flow was diminished compared with that in the older exercised animals. We conclude that aging, between 12 and 24 mo of age, and/or exercise training have only a minor effect on regional blood flow of F-344 rats during rest or cold exposure and that the enhanced thermogenesis seen in cold-exposed older exercised vs. sedentary F-344 rats cannot be explained by a greater contribution from brown fat.

Aging↗

PubMed1989

Adipose tissue dynamics during cyclic weight loss and weight gain of ground squirrels.

Ad libitum fed golden-mantled ground squirrels undergo marked annual fluctuations in body mass; during the first cycle, peak and trough masses were approximately 291 and approximately 192 g, respectively. Peak masses were significantly higher (9%) during the second than the first cycle, reflecting a 15% increase in fat-free dry mass and a 12% increase in lipid reserves. The reduction in body mass during the weight loss phase was almost entirely due to an 84% decrease in total lipid reserves and reflected a decrease in adipocyte size but not number. All measured fat depots decreased at similar rates, and there was no evidence of preferential utilization or sparing of individual depots. Fat cell size decreased progressively in each depot during the transition from peak to trough masses and did not vary among the several depots at any stage of annual cycle. Adipocyte number increased in parametrial and retroperitoneal depots but not in the subcutaneous fat between the first and second body mass peaks; fat cell size in these two depots decreased by 28 and 20%, respectively, from the first to the second peak in body mass. Reduced lipid filling of adipocytes at the second peak mass, concomitant with adipocyte hyperplasia, suggests that total lipid mass, not simply fat cell size, is regulated during the annual body mass cycle. Maturation of the subcutaneous fat depot before the initial entry into hibernation may be adaptive in providing insulation during dormancy.

Adipose Tissue↗

PubMed1989

Effect of age and gender on thermoregulation.

Previous investigations have shown that during cold exposure 24-mo-old male Fischer 344 (F344) rats do not thermoregulate as well as do 12-mo-old animals. To determine if this deficiency also occurs in female rats, we measured oxygen consumption (thermogenesis) and colonic temperature of male and female rats 5, 23, and 27 mo of age at rest and during 6 h of exposure to 6 degrees C. In addition, nonshivering thermogenesis (NST) was evaluated from the capacity of brown adipose tissue (BAT) mitochondria isolated from cold-exposed rats to bind guanosine 5'-diphosphate (GDP). Neither age nor gender had a significant effect on resting or cold-exposed oxygen consumption expressed on a mass-independent basis (l/kg body mass0.67) or on a lean body mass independent basis (l/kg lean body mass0.67). The drop in colonic temperature in response to cold was greater in the male rats. However, females exhibited increased BAT mass and relatively constant GDP binding with advancing age, whereas males showed decreased mass and GDP binding. Although the data suggest greater NST capacity in the female rats, rates of cold-induced oxygen consumption were similar in older female vs. male rats. Taken together, our data indicate that gender has a significant impact on thermoregulation and that, under the cold exposure conditions of the study, this effect involves differential heat conservation rather than heat production.

Acclimatization↗

PubMed1989

Exercise reverses depressed metabolic rate produced by severe caloric restriction.

The effects of caloric restriction and exercise on resting metabolic rate (RMR) were studied in five obese humans. Subjects consumed a 500 kcal.d-1 diet for 4 wk, with the subjects remaining sedentary during the first 2 wk and then exercising 30 min daily at 60% VO2max during the last 2 wk of caloric restriction. After 2 wk of dieting, RMR decreased to approximately 87% of the pre-dieting control value. Over the last 2 wk of dieting with the addition of daily exercise, the fall in RMR was reversed as it returned to the pre-dieting level. In summary, daily exercise reversed the drop in RMR associated with severe caloric restriction.

Adult↗

PubMed1989

Influence of maternal dietary Zn intake on expression of diabetes-induced teratogenicity in rats.

Diabetic rat pregnancies are characterized by altered maternal and fetal Zn metabolism and a higher frequency of fetal malformations. In this study, the effect of varying maternal dietary Zn on pregnancy and fetal outcome and on maternal and fetal trace element status were investigated. Starting on day 0 of gestation, streptozocin-induced diabetic and nondiabetic control rats were fed a low-Zn diet (4.5 micrograms/g diet), an adequate-Zn diet (24.5 micrograms/g diet), or a high-Zn diet (500 micrograms/g diet) throughout gestation. Fetuses were taken by cesarean section on gestation day 20. Fetuses from diabetic dams were smaller, weighed less, and had less calcified skeletons and more malformations than fetuses from control dams. In the controls, maternal dietary Zn had a minor effect on fetal malformation frequency. In contrast, in the diabetic animals, the low-Zn diet had a strong teratogenic effect. In diabetic dams, the adequate- and high-Zn diets improved fetal length and weight more than it did in fetuses from nondiabetic dams. However, supplemental dietary Zn during diabetic pregnancy did not further improve malformation frequencies. Liver and kidney Zn, Cu, and metallothionein concentrations were higher in diabetic dams than in control dams. In contrast, liver Zn, Cu, and metallothionein concentrations in fetuses of diabetic dams were lower than in fetuses from control dams, regardless of maternal dietary Zn intake. These results show that diabetes during pregnancy can amplify the teratogenic effects of a mild maternal Zn deficiency.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1988

The effect of variable magnesium intake on potential factors influencing endurance capacity.

Rats fed a magnesium (Mg) deficient diet have a lower endurance capacity than rats fed Mg adequate diets. The current study evaluates the effects of marginal, moderate, and severe Mg deficiencies on physiological and biochemical changes that may contribute to the reduced endurance capacity of Mg deficient rats. Variable levels of dietary Mg (400, 200, 100, 50 micrograms/g) were fed for 23 d to 5-wk-old male Osborne-Mendel rats. Indirect blood pressure and heart rate were measured during dietary treatment. Forty-eight hours after an endurance test, rats were killed and sampled for plasma glucose, insulin, and triglyceride levels. Organ weights, mineral and trace element concentrations, and carcass composition were determined. Blood pressure was lower in rats fed 50 and 100 ppm Mg during the first half of the study than in controls (400 ppm Mg). There were no significant differences in blood pressure among groups at the end of the study. Heart rate was not affected by dietary Mg intake. Plasma insulin was lowered by decreasing dietary Mg; however, plasma glucose and triglyceride concentrations were not affected by dietary Mg intake. Rats fed 100 and 50 ppm Mg diets had significantly higher calcium concentrations in plasma and gastrocnemius muscle than controls. Dietary Mg variably affected tissue trace element (iron, zinc, copper, and manganese) concentrations but did not affect Mg concentrations in any organ studied. Body composition was significantly altered by dietary Mg intake. In conclusion, variable Mg intake differentially affects the parameters evaluated. Thus, the decreased endurance capacity of the Mg deficient rat is apparently not the result of a single biochemical lesion but is likely to be multifactorial.

Animals↗

PubMed1988

The effect of diabetes on the molecular localization of maternal and fetal zinc and copper metalloprotein in the rat.

The molecular localization of maternal and fetal zinc and copper metalloproteins in diabetic and control rats was studied. Compared to controls, liver and kidneys of diabetic dams showed an increased concentration of zinc and copper that was associated with metallothionein. In contrast, fetuses of diabetic dams had lower zinc and metallothionein levels than fetuses from controls. The abnormal maternal trace element metabolism seen with diabetes resulted in alterations of zinc uptake and/or retention of their fetuses.

Animals↗

PubMed1988

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↗

PubMed1988

Lipectomy influences white adipose tissue lipoprotein lipase activity and plasma triglyceride levels in ground squirrels.

Golden-mantled ground squirrels undergo marked fattening and fat depletion during the prehibernatory and hibernatory phases, respectively, of their annual body weight cycle. Fat regulation was studied by surgical removal (lipectomy) of most of the inguinal-subcutaneous, retroperitoneal, and parametrial fat depots from female squirrels during the weight-gain phase of the annual cycle. Seven weeks after surgery, body weights of lipectomized (Lipx) and Sham-Lipx squirrels were equivalent, although white adipose tissue was not completely recovered in Lipx animals. Lipoprotein lipase (LPL) activity was markedly elevated in subcutaneous adipose tissue of Lipx squirrels, but not in other depots. Plasma triglyceride (TG) levels also were higher in Lipx squirrels 7 weeks after surgery. Changes in LPL activity and plasma TG may contribute to body mass and lipid restoration following lipectomy.

Adipose Tissue↗

PubMed1988

Pancreatic hypersensitivity to glucose by young obese Zucker rats (fa/fa).

Insulin secretory response to glucose was investigated in 5- to 6-week-old male Zucker obese (fa/fa) and lean (Fa/Fa) rats using a pancreatic perfusion procedure. Blood glucose response to fasting was studied in lean and obese animals over 24 hours. Plasma glucose was slightly elevated in pentobarbital-anesthetized obese rats. However, plasma insulin was 4.6 times greater than that of leans. A hypoglycemic glucose stimulus (75 mg/dL) caused pancreata from obese animals to release 6 times more insulin than lean animals. Stimuli of 125 mg/dL (normoglycemic) and 600 mg/dL (hyperglycemic) caused hypersecretion of 8 and 5 times, respectively. Hypersecretion was not accounted for solely by the twofold increase in pancreatic insulin content. Obese animals had steeper decreases in plasma glucose than lean controls during seven to 13 hours of fasting. Hypersecretion by pancreata from young obese rats to physiological levels of glucose may result in hyperphagia in order to maintain normoglycemia.

Age Factors↗

PubMed1988

Cold- and norepinephrine-induced thermogenesis in younger and older Fischer 344 rats.

Older rats exposed to low environmental temperatures show attenuated thermogenesis. However, the mechanisms responsible for this attenuation are not clear. This investigation evaluated the possibility that reduced nonshivering thermogenic capacity is associated with this attenuation. O2 consumption was measured in male Fischer 344 rats ages 7 and 24 mo at thermoneutrality (26 degrees C), during exposure to cold (6 degrees C) for 2 h, and during norepinephrine (NE) infusion (an in vivo measure of nonshivering thermogenesis). In addition, the binding of GDP to isolated mitochondria of brown fat, an in vitro estimate of nonshivering thermogenesis, was also measured. Resting mass-independent O2 consumption (ml.min-1.g body mass -0.67) was not different between the two age groups. However, mass-independent O2 consumption was significantly greater in the younger vs. older rats during 2 h of cold exposure (younger, 2.86 +/- 0.19 l/kg body mass 0.67; older, 2.39 +/- 0.10 l/kg body mass 0.67) and during 20 min of maximum NE infusion (younger, 410.4 +/- 15.1 ml/kg body mass)] was greater in younger than ml/kg body mass 0.67). Brown fat mass [absolute (g) as well as relative (g tissue/kg body mass)] was greater in younger than in older rats. Furthermore, younger rats had significantly greater binding of GDP to isolated mitochondria of brown fat than did the older rats. This effect was true whether the data were expressed as nanomoles bound per milligram mitochondrial protein (32% lower in older rats), bound nanomoles recovered (57% lower), or bound picogram per kilogram body mass 0.67 (59% lower).(ABSTRACT TRUNCATED AT 250 WORDS)

Adipose Tissue, Brown↗

PubMed1988

Effects of exercise, detraining, starvation, and refeeding on lipogenic capacity of Osborne-Mendel rat.

Both starvation and refeeding and exercise and detraining are procedures that result in lowered lipid stores followed by their refilling. Rats subjected to these procedures were evaluated for their ability to produce hepatic biosynthetic reducing equivalents. Five-week-old male Osborne-Mendel rats were exercised on a motorized treadmill for 6 wk (final speed 27 m/min, 60 min/day, 6 day/wk) or kept sedentary. Exercised and sedentary rats were starved for 48 h or fed ad libitum. After treatments, some rats in each group were killed. Remaining exercised animals were detrained or detrained and refed. Remaining sedentary rats were refed. Activities of hepatic glucose-6-phosphate dehydrogenase, 6-phosphogluconate dehydrogenase, and malic enzyme were evaluated. Plasma glucose, triglyceride, insulin, liver triglyceride, and body composition were determined. Results indicate that changes in lipids stores associated with starvation and refeeding and exercise and detraining are not associated with similar changes in enzyme activity. Starvation resulted in lowered plasma glucose, triglyceride, and insulin. Starvation and all exercise treatments resulted in lowered carcass fat. Exercised rats who were starved for 48 h and then detrained and refed for 72 h had the greatest liver weights and percent liver triglycerides. This was not associated with similar changes in enzyme activity. Increased liver lipid and decreased carcass fat may indicate a redistribution of lipid stores in these animals.

Animals↗

PubMed1988

Cold-induced thermogenesis in younger and older Fischer 344 rats following exercise training.

The inability of old rats to maintain body temperature during cold exposure has been well documented. This study evaluated the effect of exercise on the rates of cold-induced O2 consumption and the contribution of nonshivering thermogenesis (NST) to these rates. Younger (12 mo) and older (24 mo) male Fischer 344 (F344) rats were divided into exercised and sedentary groups. Exercised rats were run on a motor-driven treadmill 60 min/day, at 19-24 m/min, 5 days/wk for 6 mo. At the conclusion of the 6-mo training period, O2 consumption of all four groups was measured at thermoneutrality (26 degrees C) and during 6 h of exposure to 6 degrees C. Rectal temperatures were recorded before and after cold exposure. NST was estimated from the ability of isolated brown fat mitochondria to bind guanosine 5'-diphosphate (GDP). Core temperature of older sedentary rats fell 5.1 +/- 0.4 degrees C after cold exposure (36.3 +/- 0.3 vs. 31.2 +/- 0.8 degrees C). Exercise training in older animals prevented this fall from occurring (36.4 +/- 0.2 vs. 35.3 +/- 0.3 degrees C). Core temperatures of cold-exposed younger exercised and sedentary rats did not differ from thermoneutral values. Exercise did not alter the rates of resting body mass-independent (ml.min-1.kg body mass-0.67) O2 consumption in younger or older rats. However, body mass-independent and lean body mass (LBM)-independent (ml.min-1.g LBM-0.67) cold-induced O2 consumptions of older exercised rats were significantly elevated relative to those of older sedentary animals. This effect of exercise was not seen in younger rats.(ABSTRACT TRUNCATED AT 250 WORDS)

Adipose Tissue↗

PubMed1988

Meal-induced thermogenesis following exercise training in the rat.

The effects of treadmill exercise on the thermic effect of a meal were studied in male Sprague-Dawley rats (370 to 400 g, 4 to 5 months of age). Rats were exercised for 60 min, 5 d.wk-1 for 8 to 10 wk, at a speed of 27 m.min-1 and with a grade of 8%. Sedentary (N = 9) and exercised (N = 8) rats were given food and water ad libitum. Oxygen consumption was measured at rest and following the ingestion of a meal consisting of 81% carbohydrate, 9% protein, and 10% fat (by calories). In those animals that were exercised, oxygen consumption measurements were performed 24 h after the completion of an exercise bout. Although all animals gained weight during the experimental period, the exercised group gained significantly less than did the sedentary rats. Resting oxygen consumption [ml/(min X g body mass.67)] was not significantly different between the exercised and sedentary rats. The ingestion of the high carbohydrate meal significantly increased mass-independent oxygen consumption above resting values in both groups; the values for the exercised rats were greater than those for the sedentary rats. However, there were no differences between the exercised and sedentary rats in meal-induced oxygen consumption when the data were expressed as a function of lean body mass [ml/(min X g lean body mass)] or as mass-independent lean body mass [ml/(min X g lean body mass.67)]. These data suggest that exercise-trained rats have increased diet-induced thermogenesis and may be one factor in the loss of weight sometimes found in response to exercise.

Animals↗

PubMed1987

Thermogenic capacity and brown fat in rats exercise-trained by running.

Brown adipose tissue, a major effector of nonshivering thermogenesis (NST) in mammals, is activated by the sympathetic neurotransmitter norepinephrine. Prolonged increases in norepinephrine levels, whether elicited by cold exposure or exogenous application of catecholamines, lead to increased NST and increased thermogenic capacity of brown fat. Exercise training is also accompanied by enhanced sympathetic activity. The possibility exists that this enhancement may alter brown fat function. The present study was designed to assess the effect of a running exercise regimen on whole animal NST and the in vivo response of brown fat. Rats were trained by running on a treadmill (an average of 17 m/min, 0 degrees incline, for 90 min/d) for a period of at least 6 weeks. Whole animal NST capacity was assessed by monitoring oxygen consumption in response to infusion of norepinephrine. As a measure of the contribution of brown fat to whole body NST, the mass and norepinephrine-stimulated blood flow (microsphere technique) to the tissue were measured. None of these variables differed between the exercised (n = 10) and sedentary (n = 10) groups. That is, there were no significant differences between the two groups with respect to resting oxygen consumption, norepinephrine-induced oxygen consumption, brown fat mass, and brown fat blood flow--whether expressed per gram of tissue or as total tissue blood flow (ie, tissue mass X blood flow per gram). Further study is needed to explain the differential responses of brown fat to the increased sympathetic activity occurring during exercise v that occurring during cold exposure.

Adipose Tissue, Brown↗