Biomedical subjects

J S Stern

Publications and source records attributed to J S Stern.

At least 163 records · Page 9Linked to original sources

PubMed1985

Brown fat thermogenesis and its role in the development of obesity.

The role of brown fat thermogenesis in the development of obesity is considered from a number of perspectives. In adult rats, the impact of scapular brown fat lipectomy on carcass fat accretion was examined in three different rodent models: the Zucker lean (Fa/-) rat which is relatively resistant to obesity, the Zucker obese (fa/fa) rat which is characterized by a particularly severe form of hyperplastic obesity and the Osborne Mendel rat which remains lean on a standard pelleted diet but readily becomes obese on a palatable high fat diet. The consequences of brown fat lipectomy varied from no effect on carcass white fat accretion in Zucker Fa/- lean rats to a significant increase in adiposity in the Zucker fatty fa/fa relative to their respective sham-operated controls. The effect of the Osborne Mendel rat was intermediate between the Fa/- and the fa/fa. The results point to the importance of genetic background with respect to the impact of brown fat lipectomy on the development of white fat adiposity. In the developing Zucker rat at 2 and 8 days of age, in vivo evidence is presented to support the concept that brown fat thermogenesis is attenuated in the fatty fa/fa preobese pup. In animals of the fatty fa/fa genotype, maximum oxygen consumption in response to acute cold exposure was lower than in lean pups of the Fa/Fa genotype. Moreover, at 8 days of age, the rectal temperature of the cold-exposed fa/fa pups fell more precipitously than did that of the lean during the period of cold exposure.(ABSTRACT TRUNCATED AT 250 WORDS)

Adipose Tissue, Brown↗

PubMed1985

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

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

Animal Nutritional Physiological Phenomena↗

PubMed1985

Dietary fat intake and taste responses to fat in milk by under-, normal, and overweight women.

Dietary fat intake, with special emphasis on dairy products, was estimated from questionnaires for 42 underweight, 80 normal weight, and 64 overweight adult women. Frequency of consumption of fresh and processed meats, frozen dairy desserts, pastries, and snacks such as potato chips was greater for the overweight than for the underweight subjects. However, preferences between verbally-described high- and low-fat versions of 14 food pairs did not differ by body size. Overweight subjects reported that they consumed more non-fat milk and less whole milk than did the other groups. Discrimination, perceived intensity, paired preference, and hedonic rating of fat in milk and in chocolate milk did not differ significantly according to body size, fat intake, or type of milk consumed. Ad libitum mixing of non-fat milk and "half and half" (12% fat) to individual levels of liking also showed no significant variation with body size. However, subjects with higher dietary fat intakes mixed to higher fat-preference levels in milk than did the low- and medium-fat intake subjects. Those reporting consumption of regular milk (3.5% fat) mixed to higher fat levels than did those who consumed low-fat (2% fat) or non-fat milk. The ad libitum procedure gave better reproducibility and appeared to be a more realistic measure of liking than the hedonic rating or paired-preference tests.

Adolescent↗

PubMed1985

Protein turnover in insulin-treated, alloxan-diabetic lean and obese Zucker rats.

Obese and lean Zucker rats were made diabetic by intracardiac injections of alloxan (65-72 mg/kg body weight) and then given daily injections of protamine zinc insulin [1.25 U/(100 g/d)] for 6, 9 and 12 d. Body weight, food intake, plasma glucose and immunoreactive insulin concentrations were not different for lean and obese diabetic rats of similar ages. Rates of increase in carcass protein, mixed muscle protein and myofibrillar protein were less in obese than in lean rats. However, rates of increase for the sarcoplasmic fraction were not different. Fractional rates of synthesis of total muscle protein and myofibrillar protein, as determined by continuous intravenous infusion of [14C]tyrosine, were comparable in the two genotypes. Fractional rate of myofibrillar protein degradation, as determined by urinary 3-methylhistidine excretion, was higher in obese than in lean rats. Differences in calculated absolute rates between genotypes did not parallel differences in the fractional rates, due mainly to a smaller protein mass in obese rats. As a consequence, absolute synthetic rates were lower in obese rats, while absolute degradation rates were similar in the two genotypes. In contrast, rates of liver protein synthesis were similar in obese and lean rats, whether expressed as fractional or absolute rates. These results indicate that decreased protein deposition in the obese animal is a consequence of both an absolute decrease in protein synthesis in muscle as well as a disproportionately elevated protein degradation in muscle. Hyperinsulinemia normally seen in obese rats may be an adaptive response to minimize the impaired balance between protein synthesis and degradation.

Animals↗

PubMed1985

Dynamics of pancreatic insulin release in young Zucker rats: a heterozygote effect.

Total pancreatic insulin, dynamic insulin response to glucose (325 mg/dl), or tolbutamide (40 mg/dl) using the isolated perfused pancreas preparation and body composition were determined for 2- and 4-wk-old homozygous lean Fa/Fa, heterozygous lean Fa/fa, unknown lean Fa/??, and homozygous obese fa/fa female Zucker rats. At 2-wk, obese rats (body fat greater than 16%) released significantly more insulin than homozygous lean rats during first (min 10-16) and second phases (min 17-70) (61 vs. 30 ng and 637 vs. 255 ng, respectively). Plasma insulinemia was 177 microU/ml in obese, compared with 51 microU/ml in homozygous lean rats. The dynamic response of unknown lean followed the pattern of either the homozygous lean or the obese rats. There was no significant difference in total pancreatic insulin among any of the groups at 2 wk of age (Fa/Fa, 1.72; Fa/??, 2.01; and Fa/Fa, 1.80 micrograms). At 4 wk, the dynamic response by obese (2.98 micrograms) was similar to that of heterozygous (3.31 micrograms), both being significantly greater than the homozygous lean (1.14 micrograms) or unknown lean rats (1.77 microgram). Total pancreatic insulin in 4-wk obese (19.8 micrograms) was greater than homozygous lean rats (14.5 micrograms). Tolbutamide-stimulated insulin release was significantly greater in 4-wk obese than homozygous lean rats. Exposure to tolbutamide reduced by 60% the second-phase insulin release in both obese and homozygous lean rats during a subsequent 40-min glucose (325 mg/dl) perfusion.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1985

Brown adipose tissue lipectomy leads to increased fat deposition in Osborne-Mendel rats.

Inter- and subscapular brown adipose tissue depots were removed from nine female Osborne-Mendel rats. These lipectomized animals and nine sham-operated controls recovered from surgery for 7 days at 25 degrees C and were then placed on a highly palatable liquid diet. All animals were maintained for a 2nd wk at 25 degrees C before being switched to 8 degrees C. After 9 wk in the cold, animals were killed, and the brown adipose tissue was dissected from scapular, cervical, thoracic, perirenal, and axillary regions. Total brown fat pad mass, protein content, brown adipocyte number, citrate synthase activity, and beta-hydroxyacyl CoA dehydrogenase activity in each of the dissected brown fat depots were significantly less than those of the sham-operated controls. Thus there was incomplete metabolic compensation in the remaining brown fat depots after the removal of the scapular brown fat in the lipectomized rats. The mass and lipid content of the retroperitoneal white adipose depot were significantly increased in the lipectomized rats as was their carcass fat content (up 14%). Food intake of the lipectomized rats was slightly but significantly decreased. These data indicate that a reduction in the amount of functional brown fat is accompanied by increased body fat accretion and are thus consistent with the hypothesis that decreased brown adipose thermogenesis can lead to altered energy balance and increased white fat deposition.

3-Hydroxyacyl CoA Dehydrogenases↗

PubMed1985

Recovery of lipid mass after removal of adipose tissue in ground squirrels.

Male golden-mantled ground squirrels subjected to surgical removal of substantial portions of inguinal, retroperitoneal, and epididymal adipose tissue [lipectomy (Lipx)] or to sham lipectomy (Sham) during the early prehibernatory fattening phase did not differ in body mass 4 mo later at the time of their annual body weight peaks. Body mass restoration by Lipx squirrels was achieved without compensatory increases in food intake. There was little or no regeneration of epididymal adipose tissue, complete regeneration of the retroperitoneal depot, and an increase in mass of subcutaneous fat of Lipx animals. Epididymal and retroperitoneal adipocytes were equivalent in size in Sham and Lipx squirrels; adipocytes in subcutaneous fat were 20% larger in Lipx than in Sham animals. Generation of the annual body mass cycle of this ground squirrel involves active regulation of the lipid mass.

Adipose Tissue↗

PubMed1985

Energy expenditure is reduced in preobese 2-day Zucker fa/fa rats.

The rate of oxygen consumption was measured in 2-day Zucker preobese (fa/fa), homozygous (Fa/Fa) lean, and lean rats of unknown genotype (Fa/?) over the ambient temperature range of 26-35 degrees C. Significant differences in body mass were found among the three groups at this early age, the preobese pups having the greatest body mass. To account for body mass differences, the oxygen consumption data were expressed in terms of metabolic body size (ml O2 consumed X g body mass-2/3 X h-1). This mass-independent rate of oxygen consumption was significantly lower in the preobese pups than in the homozygous lean (Fa/Fa) pups at both thermoneutral (33-34 degrees C) and cold (26-27 degrees C) ambient temperatures at which, respectively, minimal and maximal rates of oxygen consumption were observed. This reduction in energy expenditure occurs before the establishment of hyperphagia or decreased levels of activity in the preobese pups. These data support the view that attenuated energy expenditure is a significant contributor to the early development of obesity in the Zucker fatty rat and point to the possibility of defective brown adipose tissue-mediated thermogenesis in the preobese pup.

Adipose Tissue, Brown↗

PubMed1985

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

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

Adrenalectomy↗

PubMed1985

The effect of maternal diabetes on trace element status and fetal development in the rat.

Despite improvements in prenatal care, there is a high incidence of congenital malformations in diabetic pregnancies. Not only is the diabetic patient characterized by a disorder of total fuel metabolism, but abnormal trace element metabolism occurs as well. In the present study, maternal and fetal zinc (Zn), copper (Cu), manganese (Mn), iron (Fe), magnesium (Mg), and calcium (Ca) status has been studied in Sprague-Dawley (SD) and Wistar rats. In addition, the effect of maternal diabetes on fetal development was also investigated. Rats were injected 27 days before mating with streptozocin (STZ, 45 mg/kg) in citrate buffer. On day 20 of gestation, litters were taken by cesarean section. Fetuses from diabetic dams weighed less, and had shorter crown-rump lengths and larger placentas than fetuses from controls. Evaluation of fetal skeletal development revealed fewer calcified sternal sites, anterior phalanges and caudal vertebrae, and an increased frequency of malformations in fetuses of diabetic dams. In dams, diabetics had larger adrenals, kidneys, and liver, and smaller thymus. Abnormal trace element metabolism was evident in diabetic dams and their fetuses. Mn was elevated in maternal liver, kidney and placenta of diabetic animals as well as in fetal liver of pups from diabetic dams. Maternal Cu and Zn levels were also higher in the liver and kidney of diabetic rats. In contrast, fetal liver Zn from fetuses of diabetic mothers was significantly decreased when compared with controls. These results suggest that diabetes may have induced fetal Zn deficiency. If this deficiency is present during embryogenesis/organogenesis, this could be one of the mechanisms of the teratogenicity of the diabetic state.

Animals↗

PubMed1985

The effect of brown fat removal on the development of obesity in Zucker and Osborne-Mendel rats.

Removal of significant amounts of brown fat in young Zucker rats maintained at room temperature triggered compensatory changes in the remaining brown fat depots. These changes, which occurred to a greater extent in the lean than in the obese rats, enhanced the thermogenic potential of the remaining depots, thus possibly accounting for the lack of increased adiposity in these lipectomized rats. When the Zucker rats were maintained in the cold, rather than at room temperature, their ability to compensate for removal of the scapular brown fat was compromised, particularly in the obese animals. Under such conditions, the amount of functional brown fat was significantly reduced, and the amount of body fat elevated. In the lipectomized Zucker rats, this increase in adiposity was accompanied by increased body mass. In contrast, in the cold-exposed Osborne-Mendel rats, where lipectomy was not accompanied by compensatory increases in the mass and cellularity of the remaining brown fat depots, increased body fat occurred in the absence of any increase in food intake or in total body mass.

Adipose Tissue, Brown↗

PubMed1984

Exercise training improves insulin sensitivity in the obese Zucker rat.

The effect of exercise on in vivo insulin sensitivity was examined in lean and obese Zucker rats. Rats (6 to 7 weeks of age) were swum two hours per day or kept sedentary for 8 weeks. Exercise decreased body weight gain as well as percent of fat in both genotypes. Sedentary obese rats had 62% higher gastrocnemius citrate synthase activity per gram of muscle than did lean rats. Exercise increased activity of this oxidative enzyme similarly in both genotypes. Compared to lean rats, obese rats had higher plasma-insulin levels and were less sensitive to insulin during an insulin tolerance test. Although training had no effect on plasma-insulin levels, exercise trained obese rats showed a greater drop in plasma glucose relative to sedentary controls following intravenous injection of three concentrations of insulin. It was concluded that moderate exercise training improved the insulin sensitivity of the obese Zucker rat.

Animals↗

PubMed1984

Lipoprotein lipase activity and cellularity in brown and white adipose tissue in Zucker obese rats.

The genetically obese adult Zucker rat (fafa) exhibits reduced thermogenesis when stimulated by physiological agents (cold, catecholamines). Recent evidence suggests that this thermogenic defect may be important in the manifestation of the animal's obesity and that it reflects a reduced thermogenic contribution from brown adipose tissue, the major nonshivering thermogenic site in many mammals. The present study describes the effects of the obese genotype on brown (and white) adipocyte size, number, and lipid content and tissue lipoprotein lipase (LPL) activity. In the obese rats, brown fat depots were increased in mass. This increase could be accounted for by brown fat hypertrophy (due primarily to an increase in the amount of triglyceride present in each cell) rather than hyperplasia (there being no increase in the number of brown fat cells). In addition, unlike the situation in white fat, the brown fat from the obese rats did not exhibit higher LPL activity than did the brown fat from their lean littermates. This absence of an increased capacity for triglyceride uptake, coupled with the greater amount of triglyceride per brown adipocyte, is consistent with a reduction of triglyceride oxidation (and, thus, heat production) in the cells from the obese (v the lean) rats.

Adipose Tissue↗

PubMed1984

Self-selection and the obese Zucker rat: the effect of dietary fat dilution.

Adult female lean and obese Zucker rats were allowed to compose their own diets by giving them access to three macronutrient sources. After a baseline period, the fat source was serially diluted. In all, eight concentrations of fat were used. Dilution of the fat source promoted significant increases in the intake of fat by both lean and obese rats. The increased intake of fat was not simply compensatory in nature, but rather represented significant increases in fat consumption. These results suggest that the reported increased appetite for fat of the obese rat is not a unique trait of that genotype. Further, results from this experiment demonstrate that caloric and protein regulation mechanisms may not be controlling the intake of obese and lean rats as precisely as once believed.

Animals↗

PubMed1984

Influence of dietary fatty acid concentration and geometric configuration on murine mammary tumorigenesis and experimental metastasis.

To investigate the influence of fatty acid geometric isomers on the growth and experimental metastasis of mammary tumors, mice were fed diets containing fat high in either cis or trans fatty acids. The cis fat was prepared to have a fatty acid composition similar to that of the trans fat; both were provided at 5 or 20% (by weight) of the diet. Line 168 mammary tumor cells were transplanted: 1) subcutaneously into female BALB/c mice to observe the effects of dietary fat on latency and local tumor growth, and 2) intravenously to observe influences on experimental metastasis. No differences in the latency or rate of primary tumor growth were observed among the groups fed the diets containing cis or trans fatty acids. In addition, there were no differences in fatty acid composition except the levels of trans-C18:1 in the primary tumor cells among the groups fed the experimental diets. Livers and spleens from animals fed both the 5 and 20% cis diet contained significantly more viable radiolabeled tumor cells than those fed the trans diets. Although body weight and composition were not significantly different among the groups, livers from animals fed the diets containing trans fatty acids were significantly heavier than those fed diets containing only cis fatty acids. Thus, trans fatty acids behaved similarly to cis fatty acids with respect to promotion of transplantable mammary tumor growth but trans fatty acids were less effective than cis fatty acids in promoting the blood-borne implantation and distant survival of the tumor cells.

Animals↗

PubMed1984

Blood flow into brown fat of rats is greater after a high carbohydrate than after a high fat test meal.

Postprandial oxygen uptake of whole animals and rate of blood flow into the scapular and cervical brown adipose tissue (BAT) of Osborne-Mendel male rats (200 g) were compared for those receiving a high carbohydrate meal or an equicaloric high fat meal. Blood flow was determined by the use of radiolabeled microspheres injected into the left ventricle of anesthetized animals, 2-3 hours after the test meal. In vivo oxygen uptake was elevated by about 10% (P less than 0.05) and blood flow by more than 100% (P less than 0.05) in the group receiving the high carbohydrate meal compared to the high fat meal. The rate of blood flow into tissues other than brown fat was not significantly altered by the composition of the test meal. These tissues included heart, gastrocnemius and soleus muscles, GI tract and white adipose tissue. Our data suggest that a high carbohydrate meal is more thermogenic than a high fat meal, and that the difference in the magnitude of the thermic effect produced by the two meals is paralleled by a corresponding difference in brown fat thermogenesis.

Adipose Tissue, Brown↗

PubMed1984

Exercise and detraining: effect on food intake, adiposity and lipogenesis in Osborne-Mendel rats made obese by a high fat diet.

Five-week-old male, Osborne-Mendel rats were fed a control (CON) or high fat diet (HF) (18 and 68% calories as fat, respectively). At 15 weeks of age HF rats weighed more and had a greater percent body fat than CON rats. Half the rats in each diet group were then exercised for 6 weeks on a treadmill. During exercise, food intake was unaffected in both diet groups, while body weight gain was reduced only in HF rats compared to sedentary rats. Exercise lowered fat gain and decreased lipoprotein lipase (LPL) activity in all rats, reduced in vivo lipogenesis in CON rats, and attenuated the development of obesity in HF rats. Following exercise, rats were kept inactive (i.e., detrained) for 2 weeks. Detraining increased food intake, weight gain, fat deposition and LPL activity in comparison to sedentary rats. In CON detrained rats lipogenesis returned to sedentary levels; in all detrained rats retroperitoneal fat cell number increased over that found in exercised rats. Thus, HF feeding induced obesity while exercise attenuated its development. Exercise-induced effects were not long lasting as they were reversed within 2 weeks of exercise termination as evidenced by a rapid increase in food intake, weight gain and lipogenesis.

Adipose Tissue↗

PubMed1984

Regional blood flow in rats after a single low-protein, high-carbohydrate test meal.

It was previously observed that a single low-protein, high-carbohydrate test meal results in increased in vitro thermic activity of brown adipose tissue. In the present study, we have examined whether such a meal increases the in vivo thermic activity, estimated from measurement of the rate of blood flow. With radioactively labeled microspheres, blood flows into brown fat and several other tissues were determined in meal-deprived (n = 11) and meal-fed (n = 11) rats. The microspheres were injected into the heart of anesthetized animals about 2-2.5 h after the test meal, one injection in the resting state and one during maximal norepinephrine stimulation. In the resting state, blood flow per gram tissue more than doubled in the brown fat (P less than 0.05) and was increased more than 50% in the heart (P less than 0.01) of the fed group. Blood flows into liver and retroperitoneal white fat were reduced by 40 (P less than 0.01) and 30%, respectively, in the fed group. During norepinephrine infusion, significant meal-associated increases in blood flow were evident only in brown fat (P less than 0.05) and the soleus muscle (P less than 0.05), whereas a significant decrease was observed in the liver (P less than 0.05). No statistically significant meal-associated changes in norepinephrine-stimulated blood flow were found in the other tissues examined (i.e., heart, gastrocnemius, and diaphragm muscles, kidneys, white fat, spleen, and adrenals). Our in vivo data thus support the view that brown fat plays a role in the thermic effect of a meal.

Adipose Tissue, Brown↗