Biomedical subjects

M J Stock

Publications and source records attributed to M J Stock.

At least 127 records · Page 7Linked to original sources

PubMed1985

Influence of subdiaphragmatic vagotomy and brown fat sympathectomy on thermogenesis in rats.

Infusion of rats with insulin (8 U/day via implanted minipump) for 7 days caused a 22% rise in resting oxygen consumption, which was inhibited by acute injection of the beta-adrenergic antagonist propranolol. Insulin treatment produced significant increases in brown fat mass, protein content, and total thermogenic activity (assessed from binding of guanosine diphosphate to isolated brown fat mitochondria), but these responses were inhibited by prior surgical sympathectomy of the tissue. Animals subjected to subdiaphragmatic vagotomy gained more weight than pair-fed, sham-operated controls and showed reductions in total energy expenditure, the acute thermogenic response to a meal and brown adipose tissue activity. Daily injections of insulin (1 U/day) prevented all of these effects of vagotomy. These data demonstrate that the changes in brown fat activity induced by exogenous insulin are mediated by the sympathetic nervous system and that the depressed thermogenesis and brown fat activity associated with vagotomy appear to be due to a relative insulin deficiency and can be reversed by treatment with the hormone.

Adipose Tissue, Brown↗

PubMed1985

Thermogenesis and BAT activity in hypophysectomized rats with and without corticotropin replacement.

Surgical hypophysectomy (Hypox) suppressed body weight, body energy gain, and net energetic efficiency when compared with pair-fed, sham-operated controls but caused marked increases in the thermic response to food, brown adipose tissue (BAT) mass, protein content, and BAT thermogenic activity (estimated from mitochondrial purine nucleotide binding). Chronic replacement of Hypox rats with ACTH restored adrenal weight, plasma corticosterone levels, body energy gain, energetic efficiency, and the thermic response to food to normal. However, the Hypox-replaced animals were apparently fatter (greater carcass energy density) and retained a greater mass of brown fat than controls. Purine nucleotide binding to BAT mitochondria was lower in the ACTH-replaced group than in Hypox rats but remained above the level in controls. These data indicate that hypophysectomy stimulates thermogenesis, probably as a result of decreased adrenal steroid release. However, ACTH does not totally prevent the effects of Hypox, and an involvement of other pituitary hormones and/or hypothalamic-releasing factors cannot be excluded.

Adipose Tissue, Brown↗

PubMed1985

Hormonal and metabolic responses to fasting and refeeding.

In order to help define the sequential neural, humoral and metabolic responses to feeding, an experimental model involving refeeding 3-day fasted rats a single meal has been developed. The post-prandial rise in resting oxygen consumption is taken as the metabolic end-point, but unlike the response in animals fed normally, shows a marked (24 h) delay. Using a variety of pharmacological and endocrinological techniques it has been possible to show that the delay results from a complex sequence of events involving changes in blood glucose, insulin, thyroid hormones, sympathetic activity and brown fat. The possible role of the ventomedial hypothalamus in mediating some of these events is discussed and the failure of genetically obese rats to exhibit a postprandial rise in oxygen consumption is ascribed to insulin-insensitivity.

Adipose Tissue, Brown↗

PubMed1985

Factors influencing brown fat and the capacity for diet-induced thermogenesis.

The experimental evidence for the existence and importance of diet-induced thermogenesis in laboratory rodents is reviewed, and the influence of various factors (e.g. age, genetic background, diet composition and early environment) discussed. The physiological, pharmacological and biochemical data implicating sympathetic activation of brown fat as the principal source of diet-induced thermogenesis are described, and followed by a review of the neurohumoral influences (e.g. dopamine, histamine, insulin, thyroid and adrenal steroids) on thermogenesis and brown fat activity. The possible relevance of these animal studies to human metabolism is discussed briefly.

Adipose Tissue, Brown↗

PubMed1984

Effects of histamine antagonists on noradrenaline-stimulated blood flow and oxygen consumption of brown adipose tissue in the rat.

The effects of histamine antagonists on noradrenaline-stimulated metabolic rate, tissue blood flow (estimated from the distribution of radiolabelled microspheres) and brown adipose tissue (BAT) oxygen extraction were studied in male anaesthetised rats. Injection of cimetidine (H2-receptor antagonist), reduced the noradrenaline-stimulation of metabolic rate and the increase in blood flow to BAT, but did not affect blood flow to white adipose tissue, skin, leg muscle, kidney, brain, or testes. Following noradrenaline, in vivo oxygen consumption of BAT, estimated from blood flow and oxygen extraction was depressed to 31% of control values by treatment with cimetidine, blood pressure was unaffected. Injection of the histamine (H1-receptor) antagonist, mepyramine, did not affect tissue blood flow or metabolic rate. In conscious animals, cimetidine did not affect resting oxygen consumption, but depressed the thermogenic responses to noradrenaline. These data suggest that the stimulation of BAT blood flow and thermogenesis by noradrenaline may be mediated in part by histamine acting on an H2-type receptor.

Adipose Tissue, Brown↗

PubMed1984

Chronic effects of beta 2-adrenergic agonists on body composition and protein synthesis in the rat.

Chronic treatment of rats with the beta 2-adrenergic agonists clenbuterol and fenoterol over 16-19 d raised energy intake, expenditure, and body weight gain but did not affect fat or energy deposition, and body protein gain was increased by 50 and 18%, respectively. Both drugs increased the protein content and mitochondrial GDP-binding capacity of brown adipose tissue. Clenbuterol did not affect plasma insulin, growth hormone, or triiodothyronine levels, although insulin levels were reduced by fenoterol. Both drugs caused hypertrophy of skeletal muscle (gastrocnemius), and muscle protein synthesis in vivo (fractional rate) was elevated by 34 and 26% in clenbuterol and fenoterol-treated rats, respectively.

Adipose Tissue, Brown↗

PubMed1984

Acute influences on the two GDP-binding sites in brown-adipose-tissue mitochondria.

Scatchard analysis of 3H-guanosine diphosphate (GDP) binding to rat brown-adipose-tissue mitochondria demonstrated that binding to the high- and low-affinity sites (Kd = 0.05 and 2.0 microM) was abolished by denaturation at 100 degrees C, but non-specific binding remained constant (0.2% of free-GDP). Prior incubation of mitochondria at 37 degrees C reduced binding to the high-affinity site, but this could be reversed by incubating samples at 0 degrees C. Addition of palmitic acid (5-40 nmole/mg of mitochondrial protein) did not affect GDP-binding, but similar concentrations of palmitoyl CoA caused a slight reduction in the number of high-affinity sites and a significant decrease in the number of lower-affinity sites. Acute treatments known to stimulate thermogenesis in vivo (a single meal, cold exposure, or noradrenaline injection 40-80 min before sacrifice) all increased binding to both binding sites, and tended to raise the dissociation constants, whereas injection of 2-deoxy-D-glucose, which depresses metabolic rate in the rat, decreased dissociation constants of both sites and the maximum number of high-affinity sites. These data indicate that both GDP-binding sites respond rapidly to acute thermogenic stimuli, possibly due to conformational changes in the mitochondrial inner membrane, and that palmitoyl CoA may influence mitochondrial proton conductance via an association with purine nucleotide binding sites.

Acyl Coenzyme A↗

PubMed1984

Brown fat activity in fasted and refed rats.

Four days of fasting in the rat reduced brown-adipose-tissue (BAT) mass, mitochondrial protein, and tissue protein content. Specific binding of guanosine diposphate (GDP) to BAT mitochondria was depressed by 55% in 4d-fasted rats. Rats fasted for 3 d, and then refed a single carbohydrate meal (40 kJ), showed a significant increase in specific GDP-binding (27% above fasted) 24 h later, and a large increase in total binding. Specific activities of cytochrome oxidase and alpha-glycerophosphate dehydrogenase in BAT mitochondria were not significantly affected by fasting or refeeding. These results suggest that BAT may be partly responsible for the fall in metabolic rate associated with fasting and the delayed increase after carbohydrate refeeding. These effects may be due to changes in the mitochondrial proton-conductance pathway in brown fat.

Adipose Tissue, Brown↗

PubMed1984

Influence of alcohol and sucrose consumption on energy balance and brown fat activity in the rat.

Voluntary intake of solutions of alcohol (7%) and sucrose (10%) represented 20% and 25% of total metabolizable energy intake, respectively, in young male rats maintained on a stock diet, but total energy intake was similar to that of controls drinking water. Body weight and energy gains were similar for control and sucrose-treated rats but were significantly reduced in the group drinking alcohol, and energy expenditure, corrected for body size (kJ/kg0.75/day), was elevated in rats drinking alcohol (17% above control) or sucrose (18%). Gross and net energetic efficiencies were markedly depressed by consumption of alcohol but not by consumption of sucrose. Resting oxygen consumption, before and after injection of norepinephrine (25 micrograms/100 g body weight) was similar for all groups. Brown adipose tissue (BAT) mass and mitochondrial protein did not differ between groups, but the activity of the mitochondrial proton conductance pathway, assessed from the binding of 3H-guanosine diphosphate, was significantly elevated by alcohol and sucrose consumption. Thus, the increased energy expenditure associated with alcohol and sucrose ingestion may involve BAT thermogenesis, but this alone cannot explain the larger effects of alcohol on metabolic efficiency.

Adipose Tissue, Brown↗

PubMed1984

Sympathetic and adrenocorticoid influences on diet-induced thermogenesis and brown fat activity in the rat.

Bilateral adrenalectomy markedly reduced body weight and energy gain and energetic efficiency of adult cafeteria-fed rats but enhanced the thermogenic response to food and stimulated brown fat activity. These changes were totally prevented by replacement of the animals with corticosterone (1 mg/rat/day). Unilateral denervation of the sympathetic nerves supplying the interscapular brown adipose tissue abolished the enhanced activity resulting from adrenalectomy and inhibited thermogenic activity in brown fat from cafeteria rats with intact adrenals, but had no effect in adrenalectomised animals treated with a high dose of corticosterone.

Adipose Tissue, Brown↗

PubMed1984

Effects of adrenalectomy on energy balance, diet-induced thermogenesis and brown adipose tissue in adult cafeteria-fed rats.

Feeding adult male rats a palatable cafeteria diet stimulated energy intake and expenditure but also raised body weight and energy gains. Bilateral adrenalectomy (ADX) had little effect on stock-fed animals, but prevented the development of obesity in cafeteria-fed rats by depressing food intake and energetic efficiency. Adrenalectomy also markedly increased the thermogenic activity of brown adipose tissue, and depressed insulin levels, particularly in the cafeteria group.

Adipose Tissue, Brown↗

PubMed1984

The development of obesity in animals: the role of dietary factors.

Obesity in laboratory rodents can be difficult to define, but increases in body fat content above 'normal' can be achieved by surgical or chemical lesions in the ventromedial hypothalamus, presentation of highly palatable diets (e.g. high-fat, high-sucrose or varied diets composed of human food items), or by forced-feeding. The responses to these treatments vary remarkably, depending on factors such as age, sex, early nutritional experience, genetic background, diet composition, feeding frequency and time of day or, even, of year. Many young animals can show marked increases in voluntary energy intake, but avoid obesity by simultaneously raising metabolic rate (diet-induced thermogenesis), while others show spontaneous obesity, either as they age, or at certain times of the year. It now seems that variations in both energy intake and expenditure are involved in the regulation of energy balance, and this has made the interpretation of experimental results more complicated. However, recognition of this dual control has helped to resolve many of the thermodynamic and metabolic anomalies in the literature. It is considered equally valid to adopt the same approach when describing human energy balance regulation.

Animals↗

PubMed1984

Energy balance, thermogenesis and brown adipose tissue activity in tube-fed rats.

Young adult male rats were given a portion (42%) of their normal daily food intake by stomach tube (tube-fed), but they were also allowed free access to the same powdered diet. Total metabolizable energy intake was identical to that of controls, but tube-fed rats gained 25% weight and 50% more body energy than controls over 15 days. Total energy expenditure and resting oxygen consumption, measured during the latter part of the day, were reduced in tube-fed rats. Intubated animals showed a lower thermogenic response to noradrenaline and depressed activity of the mitochondrial proton conductance pathway in brown adipose tissue (assessed from GDP-binding), but brown fat mass, protein content, the density of beta-adrenoreceptors in brown fat cell membranes and plasma triiodothyronine (T3) levels did not differ between groups. These data indicate that the enhanced energetic efficiency and fat deposition of tube-fed rats is due to a lower energy expenditure, resulting, at least in part, from lower levels of thermogenesis in brown adipose tissue.

Adipose Tissue, Brown↗

PubMed1984

Effects of denervating brown adipose tissue on the responses to cold, hyperphagia and noradrenaline treatment in the rat.

Surgical denervation of the five sympathetic nerves supplying one lobe of the interscapular brown fat of control rats caused small reductions in mass, protein content and the activity of the thermogenic mitochondrial proton conductance pathway (assessed from guanosine-5'-diphosphate (GDP) binding) when compared to the intact lobe. Denervation did not affect the acute 100% increase in mitochondrial GDP binding capacity seen after a single injection of noradrenaline. Cold-adaptation (4 degrees C for 7 days) or over-feeding (cafeteria diet for 10 days) caused marked increases in the mass, protein content and specific mitochondrial GDP binding in intact brown adipose tissue, but these changes were totally prevented by surgical denervation. These data indicate that the hypertrophy and the increased thermogenic capacity of brown fat induced by cold-adaptation or hyperphagia depend entirely upon the sympathetic innervation of the tissue.

Adaptation, Physiological↗

PubMed1984

Effect of noradrenaline on oxygen consumption and tissue blood flow in young pigs.

Metabolic rate and tissue blood flow were measured by indirect calorimetry and the radioactive microsphere technique, respectively, in anaesthetized pigs aged 10, 17, and 28 days during infusions of saline or noradrenaline. Noradrenaline produced a rise in oxygen consumption in all pigs but the magnitude of the response declined with age in Large White pigs (percent increase: 10 days old, 29.5 +/- 3.3; 17 days old, 15.3 +/- 3.2; 28 days old, 5.4 +/- 0.17) and was less in 10-day-old Minipigs (9.1 +/- 5.1). Regional blood flow per gram of tissue was similar for pigs of all ages and noradrenaline produced increases in flow to heart and skin, and small reductions in blood flow to skeletal muscle. Noradrenaline increased average blood flow to adipose tissue (four sites) by 21-fold in 10-day-old Large White pigs, but had less effect in 10-day-old Minipigs (9.5-fold) and in older Large White pigs (9-fold), where the effect on metabolic rate was diminished. It is calculated that adipose tissue could be responsible for the increase in metabolic rate during infusion of noradrenaline. Macroscopically there are no gross differences between various adipose tissue depots in the pig but those which showed the greatest response to noradrenaline correspond to areas where brown adipocytes have previously been identified by electron microscopy.

Adipose Tissue↗

PubMed1984

Tissue blood flow in control and cold-adapted hyperthyroid rats.

Chronic injections (once daily for 10-14 days) of triiodothyronine (T3) stimulated oxygen consumption by 50 and 15% in anaesthetized, control (24 degrees C), and cold-adapted (5 degrees C) rats, respectively, compared with euthyroid controls. Tissue blood flow, determined from the distribution of radioactive microspheres, was unaffected by T3 treatment in skeletal muscle, scrotum, brain, bone, skin, diaphragm, and brown adipose tissue (BAT) of rats housed at 24 degrees C, but was decreased in spleen (53% of control) and significantly increased in three white adipose tissue depots (average 267% increase) and liver (56%). Blood flow to epididymal fat and leg muscle of cold-adapted rats was increased by T3 treatment (100 and 138% increases, respectively), but other tissues were unaffected. Blood oxygen extraction and oxygen consumption in vivo by interscapular BAT was increased in hyperthyroid rats compared with euthyroid controls, but was reduced by T3 treatment in cold-adapted animals. These data show that BAT makes only a minor contribution (7%) to thyroid thermogenesis, but suggest that kidney, liver, gut, and particularly white adipose tissue may be involved.

Adaptation, Physiological↗

PubMed1984

Influence of sodium intake on thermogenesis and brown adipose tissue in the rat.

Presenting rats with a 0.9 per cent sodium chloride solution to drink instead of water had little or no effect on body weight gain and food intake, but resting oxygen consumption and total energy expenditure (corrected for body size) were elevated, and thermogenic responses to both noradrenaline and a meal were enhanced. Brown adipose tissue (BAT) mass and protein content were significantly elevated in saline treated rats, but mitochondrial GDP-binding capacity was depressed. Basal Na+, K+-ATPase activity was slightly increased in BAT homogenates from rats given saline, but noradrenaline-stimulated enzyme activity was much greater than control values. In rats drinking 1.8 per cent saline, energy intake, body weight gain and the efficiency of gain (g gain/MJ eaten) were all markedly depressed. BAT mass, corrected for differences in body size, was slightly greater than controls and the protein content of BAT was increased by 45 per cent. Rats allowed 0.9 per cent saline to drink for 7 d, and then presented with a palatable cafeteria diet, showed a more rapid rise in metabolic rate than cafeteria-fed animals drinking water. This difference was apparent only over the first 3-4 d of cafeteria feeding, and energy balance over 14 d was similar for both groups. These data show that increasing sodium intake with isotonic saline has very little effect on food intake or resting metabolic rate, but causes a marked increase in thermogenic capacity and responses to food or noradrenaline, probably because of an increase in active BAT mass. Changes in plasma ion concentrations or osmolarity, therefore, could be involved in the thermogenic response to food.

Adipose Tissue, Brown↗

PubMed1984

Thermogenic properties of ciclazindol and mazindol in rodents.

Ciclazindol, a noradrenaline (NA) uptake inhibitor originally introduced as an antidepressant, has recently been shown to produce weight loss in experimental animals and patients. Unlike CNS-stimulant anti-obesity drugs, such as amphetamine, ciclazindol may induce weight loss in animals by stimulating thermogenesis in brown adipose tissue (BAT), and it is known to stimulate resting metabolic rate (RMR) of rats and depress energetic efficiency. These effects can be achieved in the absence of overt CNS stimulation and with certain analogues of ciclazindol may be due to an exclusive peripheral action. Mazindol, a structural analogue of ciclazindol also produces an increase in RMR. However the increment is qualitatively and quantitatively different from that observed with ciclazindol and cannot be dissociated from central stimulant actions. In this report we examine some of the physiological and behavioural effects of ciclazindol and mazindol analogues in rats.

Amphetamine↗