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S J Wickler

Publications and source records attributed to S J Wickler.

32 records · Page 2Linked to original sources
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↗
PubMed1986

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↗
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

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

Isoproterenol-induced blood flow in rats acclimated to room temperature and cold.

Blood flow was measured with labeled microspheres in cold (6 degrees C)- and room-temperature-acclimated rats at rest and during infusion of the beta-agonist, isoproterenol. Isoproterenol elicited decreased mass-specific blood flows (ml . g-1 . min-1) to liver (55% of control), kidney (48%), and white fat (64%) in room-temperature-acclimated (RT) rats. Blood flow was similarly decreased in liver (51%), kidney (37%), and white fat (70%) in cold-acclimated (CA) rats. In contrast, isoproterenol increased blood flows to brown fat and cardiac and skeletal muscles. The blood flows to cardiac muscle during isoproterenol infusion were comparable in both RT (12.7 ml . g-1 . min-1) and CA (11.7 ml . g-1 . min-1) animals, representing increases of 2.9- and 2.6-fold above control values, respectively. Blood flow to skeletal muscle was also similarly elevated in RT and CA animals, representing increases 5.9 and 5.6 times those of their respective control values. In contrast, although isoproterenol greatly stimulated (ca. 8-fold) blood flow to brown fat (interscapular plus cervical depots) in RT animals, it had a greater effect on these two depots in the CA rats (18-fold increase). These data emphasize the importance of brown fat as a major effector of nonshivering thermogenesis as well as the importance of beta-adrenergic receptors in mediating the metabolic response of nonshivering thermogenesis.

Acclimatization↗
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↗
PubMed1984

Blood flow in normal and dystrophic hamsters during nonshivering thermogenesis.

The genetically dystrophic line of hamsters (BIO 14.6) has a significantly reduced capacity for nonshivering thermogenesis (NST) when compared with age-matched normal animals. Of those tissues contributing most to NST, three are altered in the dystrophic hamster (brown fat and cardiac and skeletal muscle). This study has used regional blood flows in response to isoproterenol (a potent stimulator of NST) as a measure of the potential contribution of these tissues to NST. Both isoproterenol-induced O2 consumption and cardiac output were lower in the dystrophic hamsters (13.0 +/- 0.4 vs. 18.2 +/- 0.68 ml O2 X g-0.67 X h-1 and 2.10 +/- 0.10 vs 2.98 +/- 0.16 ml X g-0.67 X min-1, respectively). Tissue blood flow was measured to brown fat, heart, skeletal muscle, liver, kidneys, adrenals, skin, and white fat. Isoproterenol was found to increase blood flows to brown fat, skeletal muscle, and cardiac muscle in normal animals and to brown fat and skeletal muscle in dystrophic hamsters, suggesting that these tissues contribute to NST. However, when corrected for body weight differences, blood flows during isoproterenol infusion to skeletal muscle and to cardiac muscle did not significantly differ between normal and dystrophic animals (2.71 +/- 0.29 vs. 3.33 +/- 0.42 and 2.81 +/- 0.25 vs. 1.85 +/- 0.24 ml X 100 g body wt-1, respectively). In contrast, normal brown adipose tissue had significantly elevated blood flows (3.50 +/- 0.39 vs. 2.28 +/- 0.27 ml X 100 g body wt-1). Thus these observations provide in vivo support for the conclusion that the reduced NST capacity of dystrophic hamsters is due, in large part, to a reduced thermogenic contribution of brown fat.

Adipose Tissue, Brown↗
PubMed1984

Scapular brown fat removal enhances development of adiposity in cold-exposed obese Zucker rats.

To investigate the contribution of brown fat (BAT) to the development of obesity in genetically obese Zucker rats (fa/fa), scapular brown fat (SBAT) was removed from obese and lean 4-wk-old females. Eight weeks after surgery there was no regrowth of SBAT. Lipectomy had no effect on body weight gain, food intake, and body composition when rats were housed at 25 degrees C. Lean rats completely compensated for the lipectomy by increasing BAT mass, protein, cellularity, and activity of citrate synthase (CS) in axillary, perirenal, and thoracic depots. beta-Hydroxyacyl-coenzyme A dehydrogenase (HOAD) activity was increased, but compensation was incomplete. In lipectomized obese rats, only BAT protein and cell number were increased sufficiently for complete compensation. In a second experiment SBAT was removed from obese and lean rats, but rats were housed in the cold (10 degrees C) for 8 wk. In lean rats, although compensation was incomplete, it was sufficient to maintain a weight gain and body composition comparable with sham-operated lean rats. In obese rats, where there was little or no compensation for lipectomy, weight gain and fat deposition were greater than observed in sham-operated obese controls. These data support the hypothesis that reducing the amount of functional BAT contributes to the development of increased adiposity.

3-Hydroxyacyl CoA Dehydrogenases↗
PubMed1983

Metabolic organization of muscle and brown fat of normal and dystrophic hamsters.

The thermogenic response to catecholamines, i.e., regulatory nonshivering thermogenesis (NST), is significantly reduced in dystrophic hamsters (BIO 14.6) compared with age-matched normals. The possibility that this reduction reflects, in part, lower levels of enzymes in those tissues implicated in NST has been examined by assaying citrate synthase (CS), beta-hydroxyacyl CoA dehydrogenase (HOAD), and phosphofructokinase (PFK), enzymes whose activity reflect the potential flux of substrates through the tricarboxylic acid cycle, beta-oxidation, and glycolysis, respectively. Each enzyme was assayed in brown fat, heart, gastrocnemius, and semitendinosus of 3-mo-old normal (n = 15) and dystrophic (n = 18) hamsters. Brown fat masses from interscapular, cervical, and scapular-axillary regions of dystrophics averaged only 50% those of normals (424 vs. 890 mg). Additionally, markers of aerobic metabolism (CS and HOAD) were significantly reduced in the brown fat from dystrophic animals. (CS activities averaged 59% of normal, whereas HOAD activities averaged 75% of normal). In dystrophic animals CS and HOAD levels were similar to those of normals in cardiac tissue but were significantly elevated in skeletal muscle samples. Tissue PFK activities were reduced only in cardiac tissue of the more affected dystrophics. Thus decreased NST capacity in dystrophic hamsters is accompanied by reduced masses and CS values in brown fat but not by decreases in the aerobic markers in skeletal or cardiac muscle.

3-Hydroxyacyl CoA Dehydrogenases↗
PubMed1983

Diminished respiratory responses of brown adipocytes isolated from BIO 14.6 dystrophic hamsters.

Catecholamine-induced thermogenesis is significantly diminished in BIO 14.6 cardiomyopathic hamsters as demonstrated by a reduced increase in oxygen consumption of these hamsters in response to administered isoproterenol. This decreased responsiveness is accompanied by a reduction in the amount of brown adipose tissue, a major nonshivering thermogenic effector. The present study demonstrates that the metabolic responses of individual brown fat cells are also altered in the dystrophic hamster. That is, 1 microM norepinephrine, the physiological mediator of nonshivering thermogenesis, evoked rates of oxygen consumption that were significantly lower in brown adipocytes isolated from the BIO 14.6 hamsters than in those from normal controls. Additionally, the dystrophic adipocytes exhibited: decreased maximal activity (per cell as well as per milligram protein) of citrate synthase; decreased cell size; and decreased amounts of protein per cell. These data indicate that the nonshivering thermogenic capacity of the intact BIO 14.6 hamsters reflects altered characteristics of the individual brown adipocytes themselves, as well as decreased amounts of the tissue.

Adipose Tissue, Brown↗
PubMed1981

Seasonal changes in enzymes of aerobic heat production in the white-footed mouse.

During seasonal acclimatization in white-footed mice (Peromyscus leucopus), there is a substantial increase in the capacity for aerobic heat production under cold stress (Mmax) in winter animals. The possibility that increases in levels of enzymes involved in aerobic heat production could be responsible for the increase in Mmax was investigated in mice captured in summer and winter. Activities of citrate synthase (CS) and beta-hydroxyacyl-CoA dehydrogenase (HOAD) and concentrations of cytochrome c (cyt c) were measured in the two primary thermogenic tissues of small mammals, skeletal muscle and brown adipose tissue (BAT). Additionally, cyt c was measured in heart, liver, and whole-body samples. CS and cyt c were used as indicators of aerobic capacity, and HOAD was used to indicate the capacity for beta-oxidation. In winter CS, cyt c, and HOAD increased (expressed per g wet mass) in skeletal muscle and BAT. There was an increase in cyt c of whole-body samples, liver, and skeletal muscle of between 55 and 78%, but no change was observed in cardiac tissue. There was an approximately 80% increase in CS and HOAD in skeletal muscle. The highly aerobic nature of BAT and its primary role in heat production are supported by the high activities in summer animals and the increase observed in winter (200, 1,570, and 220% increase in CS, HOAD, and cyt c, respectively).

3-Hydroxyacyl CoA Dehydrogenases↗
PubMed1981

Nonshivering thermogenesis in skeletal muscle of seasonally acclimatized mice, Peromyscus.

Nonshivering thermogenesis (NST) is a major contributor to total heat production capabilities of Peromyscus and the magnitude of the NST response increases dramatically in winter-acclimatized animals. To directly assess the contribution from skeletal muscle to this NST, a hindlimb perfusion system was developed for Peromyscus. Oxygen consumption was then measured with and without norepinephrine (the mediator of NST) in freshly captured animals in summer and winter. Norepinephrine (NE) was infused at 0.001, 0.01, and 0.1 micrograms . g hindlimb muscle-1 . min-1. Vascular resistance (VR), calculated as arterial pressure divided by flow rate, increased during all NE infusions. At doses of 0.001 and 0.01, VR stabilized after approximately 10 min, but at 0.1 VR continued to rise. Resting oxygen consumption was 0.817 +/- 0.037 and 0.805 +/- 0.049 mumol O2 . g-1 . min-1 in summer (n = 8) and winter (n = 7) animals, respectively. There was no apparent increase in oxygen consumption with any dosage of NE. It appears that the increase in NST in winter animals is not due to an increased NST in skeletal muscle.

Acclimatization↗
PubMed1981

Capillary supply of skeletal muscles from acclimatized white-footed mice Peromyscus.

Winter-acclimatized white-footed mice (Peromyscus leucopus) can increase their aerobic heat production under cold stress by 70%. The possibility that changes in microvascular supply might account, in part, for some of this increased thermogenic capacity was examined in one of the primary thermogenic tissues, skeletal muscle. Capillaries were stained histochemically in four hindlimb muscles of freshly captured Peromyscus in summer and winter. Capillary density, mean fiber area, and mean capillaries in contact per muscle fiber were obtained from the soleus, plantaris, gastrocnemius, and semitendinosus. If results from all individual muscles are combined, mean fiber area is significantly smaller (8%) and mean capillary density is significantly greater (40%) in winter muscles. The mean number of capillaries in contact is not different, but the mean ratio of capillaries in contact per mean fiber area (index of potential perfusion) is significantly greater (25%) in winter muscles.

Acclimatization↗