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Biomedical subjects

M J Stock

Publications and source records attributed to M J Stock.

At least 181 records · Page 10Linked to original sources
PubMed1981

Activation of brown adipose tissue thermogenesis by the ventromedial hypothalamus.

It is well established that electrical stimulation of the ventromedial hypothalamus (VMH) causes a reduction in food intake, whereas electrolytic or chemical lesions in this area result in hyperphagia and obesity in the rat. This has led to the suggestion that either the ventromedial nucleus itself, or nerve fibres passing close by, are important in the control of food intake. However, obesity due to VMH lesions occurs in weanling rats in the absence of hyperphagia and can develop in adult rats pair-fed with controls, indicating that destruction of this area also causes an increased metabolic efficiency (that is, a reduced energy expenditure). In normal rats, hyperphagia induced by feeding a highly palatable cafeteria diet is often accompanied by a large increase in heat production (diet-induced thermogenesis) which tends to prevent excessive weight gain and obesity. This diet-induced thermogenesis is due to sympathetic activation of brown adipose tissue (BAT) and we have now investigated the possibility that the VMH is involved in the activation of this process. We found that electrical stimulation of this area produced increased BAT thermogenesis, which suggests that the VMH exerts a dual influence in the regulation of energy balance--an inhibitory effect on energy intake and a stimulatory effect on thermogenesis and energy output.

Adipose Tissue, Brown↗
PubMed1981

Acute effects of food, 2-deoxy-D-glucose and noradrenaline on metabolic rate and brown adipose tissue in normal and atropinised lean and obese (fa/fa) Zucker rats.

1. Intragastric feeding (40 kJ) produced a 17% rise in metabolic rate in lean Zucker rats but only an 8% increase in obese (fa/fa) rats, and both of these responses were significantly reduced by beta-adrenergic blockade with propranolol (10 mg/kg, s.c.). 2. Parasympathetic blockade with atropine (0.5 mg/kg, s.c.) caused a doubling of the response to food in lean rats and a threefold increase in the obese mutants, such that all atropinised animals showed the same increase in metabolic rate after food. 3. Feeding also caused a significant rise in interscapular brown adipose tissue temperature, which was greatest in the lean animals and was enhanced by atropine in both groups. 4. Injection of noradrenaline (250 micrograms/kg, s.c.) caused a similar (40%) rise in metabolic rate in lean and obese animals but this response was unaffected by atropine. 5. 2-Deoxy-D-glucose injection (360 mg/kg, s.c.) depressed oxygen consumption by 25 and 8% in lean and obese rats respectively and this effect was totally abolished by atropine. 6. These results suggest that the rise in metabolic rate after a meal is partly due to sympathetic activation of brown adipose tissue. The reduced thermic response in obese Zucker rats is not due to insensitivity to noradrenaline, but may be partly due to parasympathetic inhibition of thermogenesis and partly to insensitivity to glucose availability.

Adipose Tissue, Brown↗
PubMed1981

Influence of noradrenaline on blood flow to brown adipose tissue in rats exhibiting diet-induced thermogenesis.

1. The influence of noradrenaline on regional blood flow was determined using radioactive microspheres in rats maintained on either stock diet or a palatable cafeteria diet. 2. Cardiac output and blood flow to brain, lungs, liver and skeletal muscle were similar for rats on the two diets. 3. Blood flow to total dissectable brown adipose tissue in control and cafeteria rats represented 1 and 2% of cardiac output respectively but these values rose to 7 and 15.5% during infusion of noradrenaline. 4. Arterial oxygen content was similar for all groups but the oxygen content of venous blood draining the interscapular brown adipose tissue fell to 6 ml O2/100 ml blood in control rats and 1 ml/100 ml in cafeteria rats after noradrenaline. 5. The total oxygen consumption of brown adipose tissue was calculated and found to account for 42% of the response to noradrenaline in control rats and 74% in cafeteria animals. The increments in the oxygen consumption of other tissues were almost identical in both groups and so all the diet-induced changes in thermogenic capacity can be attributed to increases in brown adipose tissue metabolism. 6. These findings demonstrate the quantitative importance of brown adipose tissue in diet-induced thermogenesis and confirm the similarities between diet and non-shivering thermogenesis.

Adipose Tissue, Brown↗
PubMed1981

Sympathetic activation of brown-adipose-tissue thermogenesis in cachexia.

Tumour-bearing mice spontaneously lose weight 8-9 weeks after implantation of a human hypernephroma, in spite of a normal food intake. Resting oxygen consumption was up to 40% higher in these animals than in sham-operated controls, but was significantly reduced by beta-adrenergic blockade with propranolol in the former group. The injection of noradrenaline caused a marked stimulation of the metabolic rate in all the animals, but the greatest response was seen in the cachectic mice. The brown-adipose-tissue mass was similar for both groups, but guanosine diphosphate binding to brown-adipose-tissue mitochondria (an index of thermogenic capacity) was significantly increased in tumor-bearing mice, and the injection of noradrenaline 1 h prior to sacrifice caused the greatest stimulation of binding in the cachectic group. These data suggest that the rapid weight loss of tumor-bearing animals may be due to a high metabolic rate which results from sympathetic stimulation of brown-adipose-tissue metabolism. The relevance of these results to cancer-induced cachexia in man is discussed.

Adipose Tissue, Brown↗
PubMed1981

A role for insulin in the diet-induced thermogenesis of cafeteria-fed rats.

Rats fed a varied and palatable "cafeteria" diet exhibited hyperphagia, increases in resting metabolic rate (VO2) and the thermogenic response to noradrenaline as well as hypertrophy of brown adipose tissue (BAT). In streptozotocin-diabetic rats, cafeteria feeding failed to produce increases in VO2 or the response to noradrenaline, although BAT mass was greater than in their respective stockfed controls. Replacement doses of insulin (protamine-zinc-insulin, PZI) at two levels (2 and 4 units/rat every alternate day) failed to restore the thermogenic response of diabetic rats to the cafeteria diet. Acute replacement (8 units PZI) 12hr before the measurements resulted in resting and noradrenaline-stimulated values for VO2 that were similar to those of non-diabetic cafeteria rats. These findings suggest an insulin requirement for diet-induced thermogenesis and the failure of diabetic rats to maintain body temperature when exposed to cold (5 degrees C) suggests a further insulin requirement for cold-induced thermogenesis. In non-diabetic cafeteria rats, plasma insulin levels were significantly lower than those of stock fed controls in spite of a high carbohydrate intake and normal blood glucose.

Adipose Tissue, Brown↗
PubMed1981

Sympathetic mechanisms in diet-induced thermogenesis: modification by ciclazindol and anorectic drugs.

1 The sympathetic noradrenergic activation of brown adipose tissue and the biochemical mechanisms involved in diet-induced thermogenesis were studied in rats. 2 A close correlation was found between brown adipose tissue Na+, K+-adenosinetriphosphatase (Na+, K+-ATPase) activity in vitro and in vivo measurements of resting oxygen consumption (VO2). The effects of noradrenaline on in vitro NA+, K+-ATPase activity in brown adipose tissue and in vivo VO2 could be mimicked by a variety of agents. These included beta-adrenoceptor agonists and agents known to induce the release of noradrenaline or inhibit the noradrenaline uptake process. The pharmacological evidence suggests that dopaminergic mechanisms may also be involved in the control of thermogenesis. 3 Amphetamine did not increase VO2 in rats without causing associated increases in locomotor activity. Ciclazindol at doses of 3-30 mg/kg intraperitoneally increased VO2 but did not appear to increase locomotor activity or evoke any other signs of CNS stimulation including lengthening of time to sleep onset or stereotypy. Separation of metabolic and CNS effects occurred only at the lowest dose of mazindol used (0.3 mg/kg i.p.). These results are probably a reflection of (a) the relative abilities of these drugs to inhibit brain and brown adipose noradrenaline uptake processes and (b) the relatively high accumulation of ciclazindol in brown adipose. 4 Of the drugs tested, only ciclazindol was a more potent inhibitor of the noradrenaline uptake system in brown adipose tissue (BAT) than in brain. Kinetic analysis also revealed that the actions of ciclazindol on the NA uptake system and Na+, K+-ATPase in BAT differed from those of mazindol. 5 These findings suggest that ciclazindol may produce an energy wasting effect in rodents without causing overt CNS stimulation; the implications of these findings in terms of human obesity are discussed.

Adipose Tissue, Brown↗
PubMed1981

Regulation of energy balance.

The past 10-15 years have produced a significant increase in knowledge and theories concerning the regulation of energy balance, but the precision of this regulation is still uncertain. However, the fact that investigators have had to resort to a variety of techniques and ploys (some of them bizarre) to produce marked pertubations in body weight is in itself an indication that the regulatory system can be very robust. Although control of food intake obviously plays a major role in this system, control of energy expenditure (i.e. DIT) also has to be considered as an important factor in the maintenance of energy balance. In this review most of the evidence for DIT and its biochemical origins has been derived from studies on experimental animals. Many of the overfeeding studies carried out on man are consistent with the animal work, but because of differences in interpretation and some equivocal results, the role of DIT in human metabolism is still a contentious issue. This problem may not be fully resolved to everyone's satisfaction until complete, continuous, and very precise energy balance measurements are made on chronically overfed lean subjects. Before this expensive and arduous experiment is undertaken, evidence for thermogenesis in man will continue to depend on acute measurements of the metabolic response to various stimuli. An increasing number of studies (e.g. 35, 80) have demonstrated the existence of NST in man, and the possibility that this could originate from BAT is supported by histological (62, 148) and thermographic data (130). Conversely, reductions in cold tolerance (2, 18) and thermogenic responses to noradrenaline (82) with increasing adiposity are similar to the blunted responses seen in genetically obese animals, which suggests that human obesity may also involve an impairment in thermogenesis. At the present time these ideas concerning the important of DIT in man and its role in obesity remain somewhat speculative, but no doubt this area will now be the subject of further research. Similarly, the impact of early nutritional influences on subsequent energy balance regulation and resistance to obesity will receive more attention following the report (144) that hyperphagia in rats during early life results in a reduced body fat content and leanness in adulthood. The relative contributions and interactions between intake and output in energy balance need clarifying, and in terms of central organization, the mechanisms of appetite control should now be considered for their relevance to the control of thermogenesis.(ABSTRACT TRUNCATED AT 400 WORDS)

Adipose Tissue↗
PubMed1980

Increased proton conductance pathway in brown adipose tissue mitochondria of rats exhibiting diet-induced thermogenesis.

It has recently been demonstrated that in rats induced to overeat by being fed a varied and palatable diet (the 'cafeteria diet') there is a marked increase in heat production which serves to reduce, or prevent, the development of obesity. This diet-induced thermogenesis is associated with increases in sympathetic activity, and with changes in brown adipose tissue. Following cafeteria feeding, brown adipose tissue hypertrophies and and exhibits increased lipolysis and an apparently greater thermogenesis in response to noradrenaline. These metabolic changes resemble those seen during non-shivering thermogenesis in cold-adapted rats, and it was proposed that non-shivering thermogenesis and diet-induced thermogenesis have a similar metabolic origin which depends on the unique capacity of brown adipose tissue for thermogenesis. During non-shivering thermogenesis heat is produced in brown adipose tissue through a proton conductance pathway across the inner mitochondrial membrane that dissipates the proton gradient generated by respiration. The activity of the proton conductance pathway can be modulated by purine nucleotides, and changes in the pathway seem to be related to the level of purine nucleotide binding to brown adipose tissue mitochondria. We now report results which indicate that the proton conductance pathway is augmented in cafeteria-fed rats, and suggest that it operates to dissipate their excess energy intake through diet-induced thermogenesis

Adipose Tissue↗
PubMed1980

Effects of fasting and refeeding on the metabolic response to a standard meal in man.

Measurements of resting and exercising metabolic rate were made on eight subjects (five male, three female) before and after consumption of a standard liquid meal (1.67 MJ). This test was conducted after a day of complete fast and again after a day of overeating (average intake, 19.8 MJ). There were no significant changes in resting or exercising metabolic rate due to the previous day's energy intake. The resting thermic effect (post-prandial rise in metabolic rate) of the standard meal was similar on both test days but the exercising thermic effect was 50% greater after the day of overeating. It was concluded that the metabolic response to food in exercising subjects may be affected by the previous day's energy intake but the overall energetic efficiency of the body at rest and during exercise is unaffected.

Adult↗
PubMed1980

The measurement of food and energy intake in man-an evaluation of some techniques.

A dietary survey was carried out on an Antarctic base over a period of 6 to 12 months on twelve individuals. Three methods of determining individual food and energy intake were used-weighing and recording of food as eaten in combination with food tables, dietary recall, and bomb calorimetry of duplicate meals. Use of weighed food intakes and food composition tables underestimated energy intake by 7% when compared to analysis of duplicate meals by bomb calorimetry. One week was found to be the most practical period over which intake should be measured to determine "habitual" food intake.

Adult↗
PubMed1980

The measurement of daily energy expenditure--an evaluation of some techniques.

An energy balance survey was conducted on an Antarctic base on 12 individuals for periods varying between 6 and 12 months. Energy expenditure was estimated using two activity/dairy card techniques and mean 24-hr heart rate used in conjunction with a variety of derived heart rate/energy expenditure regression equations. The accuracy of the various techniques was determined by comparison with estimates obtained using energy intakes and changes in body fat. No method of measuring energy expenditure was accurate enough to predict fat gain or loss. Errors in individuals were large and random but the mean error in the estimation of energy expenditure of the community was reasonable. When using the dairy card there was no difference between using measured values for energy costs of specific activities and using values taken from the literature. Using heart rate was no less accurate than the diary card if energy expenditure was predicted from a regression line derived from heart rate and log energy expenditure, and the technique was more acceptable to the subjects.

Adipose Tissue↗
PubMed1980

A longitudinal study of body weight and body fat changes in Antarctica.

Body weight and body fat changes (calculated from skinfold thickness) that occurred in a male population spending a year on an Antarctic base are described. There was a marked individual variation in patterns of weight and fat changes between seasons but mean values for the whole community showed little change over the year. Combining skinfold and body weight measurements revealed probable individual differences in fat gain or loss with weight gain and loss, but the role of changes in total body water or fat-free mass could not be determined. The possibility of combining long-term measurements of body fat and energy intake to provide an estimate of energy expenditure is discussed.

Adipose Tissue↗
PubMed1980

Effects of manipulating dietary protein and energy intake on energy balance and thermogenesis in the pig.

Weight maintenance was achieved by feeding either restricted amounts of a high-protein diet (HP) or ad libitum amounts of low-protein diet (LP) to 6 and 20 kp pigs for up to 42 days. In all cases, LP animals consumed approximately three times as much energy as the HP animals but in the 20-kp pigs, almost all (70%) of this excess was deposited in the carcass as fat. In 6-kg pigs fed the LP diet, changes in body energy content accounted for only a small fraction (27%) of the total energy intake; a large difference in energy expenditure was seen between these animals and the HP group, which was attributed to differences in dietary-induced thermogenesis. Six-kilogram LP pigs showed elevated plasma triiodothyronine levels and hepatic mitochondrial alpha-glycerophosphate dehydrogenase activity and an enhanced sensitivity to the in vitro lipolytic effects of norephinephrine (NE) on adipose tissue. These changes are similar to those observed in rats exhibiting dietary-induced thermogenesis and the relevance of these findings to the increased heat production of LP pigs is discussed.

Adipose Tissue↗
PubMed1979

A role for brown adipose tissue in diet-induced thermogenesis.

Measurement of energy balance during voluntary overeating in rats unequivocally establishes the quantitative importance of diet-induced thermogenesis in energy balance. Like cold-induced thermogenesis, this form of heat production involves changes in the activity of the sympathetic nervous system and brown adipose tissue which suggest that this tissue may determine metabolic efficiency and resistance to obesity.

Adipose Tissue, Brown↗