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Biomedical subjects

M J Stock

Publications and source records attributed to M J Stock.

At least 109 records · Page 6Linked to original sources
PubMed1986

Activation of thermogenesis of brown fat in rats by baclofen.

Injection of baclofen (0.5-5 micrograms) into the ventromedial hypothalamus (VMH) of anaesthetized rats produced marked increases in the temperature (over 2 degrees C) and thermogenic activity of brown adipose tissue (BAT). These effects were abolished by ganglionic or beta-adrenergic blockade, or denervation of the tissue, but unaffected by hypophysectomy, adrenalectomy or vagotomy. Injections into the hypothalamus close to, but outside the ventromedial hypothalamus did not affect brown adipose tissue. Intravenous administration of baclofen produced similar increases in the temperature of brown adipose tissue, but at larger doses (50-1000 micrograms), and a subcutaneous injection stimulated the metabolic rate in conscious rats. Chronic treatment with baclofen suppressed weight gain and stimulated activity of brown adipose tissue without affecting food intake. These effects of baclofen, which were not mimicked by injections of gamma-aminobutyric acid (GABA), indicate a novel action of baclofen in the ventromedial hypothalamus, leading to marked increases in metabolic rate and body temperature by stimulating sympathetic outflow to brown fat.

Adipose Tissue, Brown↗
PubMed1986

Spontaneous and experimental variations in body weight, food intake and metabolic rate in captive dormice (Glis glis).

Captive dormice (Glis glis) showed spontaneous cyclical fluctuations in body weight that were not synchronous between animals and not directly related to season. Presenting the animals with a varied and palatable (cafeteria) diet for short periods caused marked increases in energy intake and body weight, and higher levels of oxygen consumption (V02). The level of hyperphagia was fairly constant, but the rise in V02 during cafeteria feeding varied (20-80%) according to season, being greatest in the winter (Nov.-Jan.). Removal of the cafeteria foods caused weight loss, hypophagia and a fall in V02 to levels below that seen in either normally-fed or fasted dormice. This hypometabolism was associated with increased periods of sleep and torpor, and it is suggested that the excess fat deposition resulting from cafeteria feeding may have induced a transient "hibernation-like" state.

Animals↗
PubMed1986

Influence of environmental temperature on energy balance, diet-induced thermogenesis and brown fat activity in 'cafeteria'-fed rats.

1. Young male rats were fed on a pelleted stock diet or a variety of palatable food items ('cafeteria' diet) and housed at 24 degrees or 29 degrees. 2. 'Cafeteria' feeding at the lower temperature stimulated energy intake, gain and expenditure, but reduced energetic efficiency such that over 70% of the excess intake was expended. 3. Housing at 29 degrees suppressed intake and expenditure in animals on both diets, but to a greater extent in 'cafeteria'-fed rats and energetic efficiency was greater than control values at this higher temperature. 4. The thermogenic capacity of brown fat (mitochondrial purine nucleotide binding) was increased by 'cafeteria' feeding, but was suppressed in animals kept at 29 degrees. 5. The results demonstrate that diet-induced thermogenesis is inhibited by high environmental temperatures.

Adipose Tissue, Brown↗
PubMed1986

Thermogenesis and sympathetic activity in BAT of overfed rats after adrenalectomy.

Resting oxygen consumption was elevated by 30% in young rats fed a cafeteria diet compared with their chow-fed controls and by 22% in cafeteria-fed, adrenalectomized (ADX) rats compared with the ADX chow-fed group, but injection of propranolol reduced oxygen consumption in the cafeteria-fed animals and abolished these differences. Brown adipose tissue (BAT) mass was increased by cafeteria feeding, and the activity of the mitochondrial proton conductance pathway (assessed from purine nucleotide binding) was enhanced by adrenalectomy and by cafeteria feeding. Norepinephrine turnover in BAT (determined from the time-dependent loss of tissue [3H]norepinephrine specific activity) was increased by 105% in sham-operated, cafeteria-fed rats, by 142% in chow-fed ADX rats, and by 400% in cafeteria-fed ADX rats, compared with chow-fed controls. Cardiac norepinephrine turnover was elevated by 80% in sham-operated, cafeteria-fed rats, but unaffected by adrenalectomy. These data indicate that the enhanced thermogenesis and BAT activity induced by adrenalectomy in chow- or cafeteria-fed rats is due to increased sympathetic activity in the tissue.

Adipose Tissue, Brown↗
PubMed1986

Body weight and brown fat activity in hyperphagic cafeteria-fed female rats and their offspring.

Presenting pregnant rats with a varied choice of human food items (a cafeteria diet) caused a slight reduction in total protein intake and significant increases in energy intake (32%) and weight gain compared to pregnant females fed stock diet (controls). Cafeteria-fed mothers gave birth to the same number and weight of pups as controls, and these grew normally, but were fatter at weaning than control pups. Cafeteria-fed dams lost more weight than controls during lactation, in spite of sustained hyperphagia, and body fat and energy was the same as controls at 21 days post-partum. Brown adipose tissue protein content and thermogenic activity (assessed from mitochondrial purine nucleotide binding) were both elevated in cafeteria-fed mothers when compared to controls at 21 days post-partum, but brown fat activity in their offspring at weaning did not differ between treatments, although tissue protein content was depressed in the pups of cafeteria-fed dams.

Adipose Tissue, Brown↗
PubMed1986

The role of brown fat in diet-induced thermogenesis.

Laboratory rodents can be induced to overeat voluntarily when exposed to a choice of highly palatable human foods so-called "cafeteria diet". The hyperphagia of these animals is associated with marked increases in energy expenditure and reduced levels of energetic efficiency. Increases in Diet-Induced-Thermogenesis (DIT) in response to overfeeding have been demonstrated in several species including man. The studies with the cafeteria-fed rats confirm the large potential for DIT in young animals. In older (26-week-old rats) a dramatic decline in the capacity for DIT is observed. Increases in energy expenditure resulting from hyperphagia appear to be mediated by the sympathetic nervous system, which causes activation of heat production in brown adipose tissue (BAT). The high thermogenic potential of BAT is due to the physiological uncoupling of oxidative phosphorylation in the inner mitochondrial membrane. This activity is enhanced by overfeeding, which causes hypertrophy. DIT and BAT are controlled by hormonal action: noradrenaline appears to be the primary activator of BAT and insulin may be required for DIT and may even activate thermogenesis. Other hormones such as glucagon, thyroid, melatonin, TSH, endorphins and sex hormones are also implicated in one way or another in the regulation of energy balance and the control of thermogenesis.

Adipose Tissue, Brown↗
PubMed1985

Changes in adrenoreceptor density in brown adipose tissue from hyperthyroid rats.

Treatment of rats with triiodothyronine (T3 10 micrograms/100 g per day, 20 days) increased the mass of brown adipose tissue (BAT) and heart ventricle and stimulated beta-adrenoreceptor number (assessed from radioligand binding) by 43% in isolated BAT and heart membranes. alpha-Receptor number was slightly increased in BAT membranes (42%) but reduced in heart from T3-treated rats. The ratio of alpha-receptors/beta-receptors was unaffected by T3 treatment in BAT membranes (control and hyperthyroid = 1.54) but reduced in heart (control = 2.8, T3 = 1.04).

Adipose Tissue, Brown↗
PubMed1985

Modification of body composition by clenbuterol in normal and dystrophic (mdx) mice.

Female dystrophic mice (mdx on C57 Black background) gained weight more rapidly than age-matched controls and had a higher body fat content (% body weight), a slightly lower protein content and a reduced mass of muscle. Chronic treatment (21 d) of the mice with the beta 2-agonist clenbuterol stimulated weight gain in both genotypes without affecting energy intake. Clenbuterol increased the mass of the gastrocnemius and soleus muscle by 13% and 29% in normal and dystrophic mice, respectively, and raised body protein but depressed body fat. Body water and energy content were unaffected by clenbuterol, but the ratio of protein to fat in the carcasses was enhanced by 17% in normal and 56% in dystrophic mice following clenbuterol treatment. Thus, the beta 2-agonist restored the body composition of dystrophic mice to normal and enhanced the protein to fat ratio in both these and normal mice.

Animals↗
PubMed1985

Involvement of insulin in the acute thermogenic responses to food and nonmetabolizable substances.

Gastric intubation with 40 kJ of a carbohydrate slurry (4 mL) produced increases in resting oxygen consumption (VO2) of 15% to 22% in control, cold-adapted, and hyperthyroid rats, but the absolute rise in metabolic rate after food was greater in the latter group. Tube-feeding methyl cellulose (4 mL, 7% wt/vol) evoked similar increases in VO2 to carbohydrate (15% to 23%), but all of these responses were inhibited by beta-adrenergic blockade with propranolol. In cold-adapted animals, fat (40 kJ, 1.2 mL) produced a greater thermic effect than carbohydrate or methyl cellulose, and water (4 mL) also induced a small (8%), significant increase in VO2. Treatment with diazoxide shortly before the meal, to inhibit insulin release, almost completely inhibited the thermic responses to carbohydrate and methyl cellulose in all groups, but did not alter the effects of fat or water. Ingestion of a nonmetabolizable substance (methyl cellulose), would appear to stimulate metabolic rate to a similar extent to carbohydrate, possibly by causing gastric distention. Thermic effects of both these substances appear to involve insulin release and activation of the sympathetic nervous system. The thermic response to fat can also be inhibited by beta-adrenergic blockade, but apparently does not involve insulin release.

Acclimatization↗
PubMed1985

Energy balance and brown fat activity in rats fed cafeteria diets or high-fat, semisynthetic diets at several levels of intake.

The object of the study was to determine the relative effects of hyperphagia and diet composition on energy balance and thermogenic activity in rats fed highly palatable cafeteria diets. Three types of diet were used: a pelleted stock diet, a cafeteria diet composed of a variety of human food items, and semisynthetic diets with nutrient compositions similar to the stock and cafeteria diets. Feeding rats a high-fat semisynthetic diet (similar to the cafeteria diet) at a energy intake equivalent to that of stock-fed controls (approximately 2.5 times maintenance) resulted in greater body energy gains and energetic efficiencies. These effects were probably due to the reduced energy costs of fat synthesis associated with high-fat diets. No effect of dietary composition on body energy gain was seen in animals fed below 2.5 times maintenance. Animals fed four cafeteria food items each day, or the high-fat semisynthetic diet, at 2.5 times maintenance showed significantly greater thermogenic responses to norepinephrine, increased brown adipose tissue (BAT) mass, and greater BAT mitochondrial GDP binding than controls on the same intake. Injection of propranolol reduced oxygen consumption in all groups, but the effect was greater in animals on higher intakes and was highest in the cafeteria groups. Thus, increasing fat intake, either by presenting cafeteria food items or by feeding a high-fat semisynthetic diet at the same level of intake as controls, stimulates the sympathetic nervous system and BAT activity.(ABSTRACT TRUNCATED AT 250 WORDS)

Adipose Tissue, Brown↗
PubMed1985

Acute and chronic effects of ACTH on thermogenesis and brown adipose tissue in the rat.

A single injection of ACTH stimulated metabolic rate in the rat, and this effect was enhanced in hyperphagic cafeteria-fed rats. Chronic treatment with ACTH significantly reduced body weight, energy gain and energetic efficiency in stock-fed rats. Thermogenic responses to noradrenaline and a single meal, and purine nucleotide (GDP) binding to brown adipose tissue (BAT) mitochondria were also increased. Cafeteria feeding induced hyperphagia, increases in metabolic rate, acute thermogenic responses and BAT activity, and depressed energetic efficiency. ACTH had no additional effects on energy balance, thermogenic responses or brown fat in cafeteria-fed rats. These data indicate that stimulation of thermogenesis and BAT activity by ACTH resembles that induced by hyperphagia, and this effect may be partly responsible for the changes in energy balance after adrenalectomy seen in previous studies. However, acute and chronic responses to ACTH depend upon the nutritional status of the animal.

Adipose Tissue, Brown↗
PubMed1985

Biological distribution and significance of brown adipose tissue.

1. The structure, location, identification and thermogenic function of brown adipose tissue is discussed before describing its distribution in animals. 2. With a few interesting exceptions, brown fat occurs almost exclusively in mammals. 3. This tissue has been positively identified in thirteen orders, but more thorough investigations are required before its absence can be confirmed in the remaining eight mammalian orders. 4. Factors influencing the amount and activity of brown fat seen between and within species are numerous, but some of the most important are body size, diet, environmental temperature, age and reproductive state. 5. The role brown fat, and the effects of impairments in its function, are described in relation to thermoregulation and the control of energy balance and body composition.

Adipose Tissue, Brown↗
PubMed1985

Thermogenic capacity and brown adipose tissue activity in the common marmoset.

Resting oxygen consumption was measured in anaesthetized male and female common marmosets (Callithrix jacchus) at 29 degrees C. Injection of noradrenaline caused a marked increase in oxygen consumption (63%), but this response was lower in males. Large deposits (750 mg) of brown adipose tissue (BAT) were dissected from the cervical, subscapular, axillary and perirenal areas. High levels of guanosine diphosphate binding to isolated brown fat mitochondria were observed, indicating that the thermogenic proton conductance pathway is very active in brown fat from the marmoset. High levels of brown adipose tissue thermogenesis in these animals may be related to a requirement for diet-induced thermogenesis.

Adipose Tissue, Brown↗
PubMed1985

Baclofen is a potent activator of brown fat metabolism.

The injection of (+/-)-baclofen intravenously or directly into the ventromedial hypothalamus of urethane-anaesthetized rats, produced an activation of brown fat metabolism. This was seen as an increase of brown fat and rectal temperatures, and an increase of GDP binding in brown fat mitochondria. The activation was mediated by the sympathetic supply.

Adipose Tissue, Brown↗
PubMed1985

Effects of subdiaphragmatic vagotomy on energy balance and thermogenesis in the rat.

Subdiaphragmatic vagotomy caused chronic gastric distension and hypertrophy, and a reduction in voluntary food intake in rats fed a pelleted stock diet. These effects were minimized by feeding a more digestible semisynthetic diet. Vagotomized rats fed the pelleted diet showed lower rates of oxygen consumption than pair-fed controls, and the rise in metabolic rate (thermic response) following gastric intubation with a carbohydrate meal was diminished. This could be restored to normal by simultaneous injection of insulin. Thermic responses to fat and noradrenaline were normal in the vagotomized group. On the powdered semisynthetic diet, vagotomized rats gained more weight and showed greater efficiency of energy gain than pair-fed controls. The thermic response to a single meal of the semisynthetic diet was depressed in these vagotomized rats, but restored to normal by acute insulin treatment. The activity of the thermogenic proton conductance pathway in brown adipose tissue mitochondria (assessed from purine nucleotide binding) was reduced by vagotomy in animals on both diets, but was restored to normal by chronic insulin treatment, which also slightly raised brown fat activity in sham-operated rats. These results demonstrate that the reduced gastric activity and food intake following vagotomy is dependent on the digestibility and/or composition of the diet. When differences in food intake are abolished by pair feeding, vagotomy reduces thermogenic responses to carbohydrate, probably as a result of impaired insulin release. This may be responsible for the enhanced energetic efficiency and elevated weight and energy gains seen after vagotomy.

Adipose Tissue, Brown↗
PubMed1985

Beta-adrenoreceptors in rat brown adipose tissue: proportions of beta 1- and beta 2-subtypes.

Binding of (-)-[3H]dihydroalprenolol [( 3H]DHA) to isolated brown adipose tissue (BAT) microsomal membranes was used to estimate beta-adrenoreceptor density, and this was found to be saturable, reversible, and stereospecific. Scatchard analysis indicated a single class of binding sites of equilibrium dissociation constant 2.2 nM, with a maximum number of binding sites of 160-170 fmol/mg protein. These values were unaffected by the age or sex of the animals, and similar Kd values were obtained for binding to heart and lung membranes. The kinetically derived Kd from forward and reverse reactions was 1.4 nM for BAT. Hofstee analysis of displacement of [3H]DHA produced linear plots for propranolol but curvilinear plots for atenolol and ICI 118,551. Atenolol showed 50-fold selectivity for beta 1-receptors and ICI 118,551 50-fold selectivity for beta 2-receptors in heart, lung, and BAT membranes. These plots indicated beta 1:beta 2-receptor ratios of 59:41 for BAT and heart and 25:75 for lung. It is possible that both beta-adrenoreceptor subtypes in BAT may be involved in the activation of thermogenesis in the tissue.

Adipose Tissue, Brown↗