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Biomedical subjects

M J Stock

Publications and source records attributed to M J Stock.

At least 73 records · Page 4Linked to original sources
PubMed1991

Hypothalamic regulatory peptides in obese and lean Zucker rats.

1. Hypothalamic concentrations of nine peptides with experimental effects on energy balance were compared in obese (fa/fa) and lean (Fa/?) male Zucker rats. To determine whether any peptide differences between obese and lean rats might be due to the overweight condition per se, separate groups of obese rats were food-restricted to reduce their body weight to lean values. 2. Concentrations of neuromedin B, a bombesin-like peptide, in the central hypothalamus were significantly higher in obese than in lean rats. This difference was not affected in food-restricted obese rats. 3. Hypothalamic levels of neuropeptide Y, an extremely potent central appetite stimulant, were similar in lean and freely fed obese rats but central hypothalamic levels of neuropeptide Y rose significantly in food-restricted obese rats. 4. These findings suggest that disturbances in hypothalamic neuromedin B concentrations may be involved in the obesity syndrome of the fa/fa Zucker rat. Increased central hypothalamic levels of neuropeptide Y in food-restricted rats suggest that this peptide may help to defend body weight by stimulating eating after weight loss.

Animals↗
PubMed1991

Thermogenic responses to selective and nonselective beta-adrenerg agonists in hypothyroidism of Sprague-Dawley rats.

Resting oxygen consumption (VO2) and mitochondrial GDP binding were measured in hypothyroid and euthyroid rats after administration of selective and nonselective beta-adrenoceptor agonists (BRL 35135A and Isoprenaline--BRL, ISO). Resting VO2, VO2 increment and mitochondrial GDP binding after beta-agonists were lower in hypothyroid rats than in the euthyroid group. The reduced response was more marked for ISO than for BRL. These results suggest that BRL is acting on a beta-adrenoceptor which differs from beta-1 and beta-2 adrenoceptors, responsible for the effect of ISO. Activation of thermogenesis via this beta-3 adrenoceptor seems to be less dependent on permissive levels of thyroid hormones than on activation via beta-1 and/or beta-2 adrenoceptors.

Adipose Tissue↗
PubMed1990

Effects of hypothyroidism and hyperthyroidism on thermogenic responses to selective and nonselective beta-adrenergic agonists in rats.

Oxygen consumption (VO2) and mitochondrial guanosine diphosphate (GDP) binding of interscapular brown adipose tissue (BAT) were measured in hypothyroid, hyperthyroid and euthyroid rats after stimulations with selective and nonselective beta-adrenoceptor agonists: BRL 35135A (BRL) and Isoprenaline (ISO). Resting VO2, VO2 increment and mitochondrial GDP binding after beta-adrenergic stimulations were lower in hypothyroid rats than in the euthyroid group. The reduced responses were more marked for ISO than for BRL. Restion VO2 and VO2 increment after beta-adrenergic stimulations were higher in hyperthyroid rats than in the eurthyroid group; the increment was more marked for BRL than for ISO. In hyperthyroidism, mitochondrial GDP binding after BRL and after ISO was in the same magnitude; it was higher in the hyperthyroid than in the euthyroid group after BRL but not after ISO. The different thermogenic responses after ISO and BRL stimulations suggest that BRL is acting on a beta-adrenoceptor differing from the beta-1 and beta-2 adrenoceptors responsible for the effects of ISO. Activation of thermogenesis via the beta-3 adrenoceptor seems to be less dependent on the permissive levels of thyroid hormones than activation via beta-1 and/or beta-2 adrenoceptors. The beta-3 adrenoceptor may be more sensitive to increased levels of thyroid hormones.

Adipose Tissue, Brown↗
PubMed1989

Non-protein energy source in parenterally fed weanling rats influences growth, body composition, and skeletal muscle protein turnover.

Comparison was made between three total parenteral nutrition (TPN) regimens given to young, weanling rats for 5 days. The three isoenergetic and isonitrogenous regimens contained different ratios of glucose to lipid as non-protein energy sources, being composed of 100% glucose; 67% glucose/33% fat; and 50% glucose/50% fat respectively. Amino acid content was identical for each regimen. Body weight gain, carcass water and energy content, and in vitro skeletal muscle protein synthesis and degradation rates, were measured. All rats gained weight, but those receiving TPN with 100% of non-protein energy as glucose gained the most wet (live) and dry weight. Energetic efficiency was also significantly higher in this group. However, carcass analysis showed that much of the weight gain in this group was probably due to fat deposition. Although the two TPN groups receiving fat emulsion in addition to glucose gained less weight and had lower energetic efficiencies, weight gain was achieved with a comparatively smaller increase in fat deposition compared to the glucose-only group. In vitro rates of protein synthesis in skeletal muscle were significantly higher in the group receiving 100% glucose, but protein degradation rates in this group were grossly elevated. Protein synthesis rates in the groups receiving lipid were less, but degradation rates were also lower. The results suggest that optimal net protein balance in skeletal muscle was achieved in the group receiving 67% glucose: 33% lipid as the non-protein energy source.

Journal Article↗
PubMed1989

Pyrogenic and thermogenic effects of interleukin 1 beta in the rat.

Single injections of recombinant human interleukin 1 beta (IL-1 beta) caused large (up to 2 degrees C) and sustained (3 h) increases in body temperature in conscious rats. Intracerebroventricular injections (10-100 ng) were much more effective and elicited greater responses than intravenous injections (0.1-1 microgram). IL-1 beta increased resting oxygen consumption by 25-49% in a dose-dependent manner. The activity of the thermogenic proton conductance pathway in brown adipose tissue (BAT) mitochondria was assessed from purine nucleotide (GDP) binding and was elevated by 40 and 86% 1 h after intravenous (1 microgram) or intracerebroventricular (100 ng) injection of IL-1 beta, respectively. Regional tissue blood flow was determined in anesthetized rats from the distribution of radiolabeled microspheres. Blood flow to liver (hepatic arterial), testes, skin, and white adipose tissue was unaffected by IL-1 beta injection. Blood flow to brain and kidney was increased (142 and 50%) but reduced (58%) to skeletal muscle after intravenous but not intracerebroventricular injection of interleukin. In contrast, blood flow to BAT was markedly elevated after intravenous (288%) or intracerebroventricular (382%) injection of IL-1 beta. Severing the sympathetic nerves supplying the interscapular BAT depot prevented the increase in blood flow. These data indicate that the potent pyrogenic effects of IL-1 beta in the rat are due largely to a central action. Fever is associated with increases in metabolic rate and BAT activity, and these results provide support for the involvement of brown fat in thermogenesis associated with fever.

Adipose Tissue, Brown↗
PubMed1989

Surgical removal of brown fat results in rapid and complete compensation by other depots.

Interscapular, scapular, and cervical brown adipose tissue (BAT) depots were removed from young male rats (BATX). These depots represented 40% of both the total dissectible mass and cytochrome oxidase content of BAT in these animals. Sham-operated and BATX rats were fed a low (8%) protein diet for periods of 9 or 16 days. Over both periods, body weight gain and energy intake, gain, expenditure, and efficiency were almost identical in sham and BATX groups. Four days after lipectomy the maximal thermogenic response (increase in O2 consumption) to norepinephrine (400 micrograms/kg sc) was 30% lower for BATX rats than for controls, but by day 13 this difference had disappeared. Nine days after lipectomy the total mass and cytochrome oxidase activity of the remaining dissectible BAT was comparable to that of the sham-operated controls, although the protein content was slightly reduced. The specific mitochondrial GDP binding (an index of thermogenic activity) was increased significantly in BATX rats, and total BAT mitochondrial GDP binding was no different from control values. At the end of the experiment (day 16), no regeneration of excised tissue had occurred, but the remaining BAT depots had shown almost complete compensation; the mass and the oxidative and thermogenic capacity of the total dissectible brown fat were virtually identical in both groups.

Adipose Tissue, Brown↗
PubMed1989

Thermogenesis and brown fat: relevance to human obesity.

Brown adipose tissue (BAT) is a specialized thermogenic tissue, which is highly vascularized and richly innervated with sympathetic nerves. Due to the high thermogenic capacity (500 W/kg) even very small quantities such as those found in adult man can significantly influence het production. As little as 50 g BAT could make a contribution of 10-15% to energy turnover in man. This would be more than sufficient to cause large differences in fat deposition between individuals with active or inactive dietary induced thermogenesis. Recent research has revealed the presence of an atypical beta-adrenoreceptor on BAT, tentatively designated as beta 3-adrenoreceptor. The development of beta 3-agonists offers an opportunity to treat obesity without the cardiovascular and other undesirable side-effects of conventional adrenergic agonists.

Adipose Tissue, Brown↗
PubMed1989

Effects of low (LCD) and very low (VLCD) energy diets on metabolic rate and body composition in obese (fa/fa) Zucker rats.

This study was designed to test the effects of reducing body weight by restricting the energy intake of obese rats to levels equivalent to human low (LCD) and very low (VLCD) calorie diets. Two groups of weight-matched obese Zucker rats were fed either 3 g/day of the Cambridge diet (VLCD group), or 11 g/day of a stock diet (LCD group) until their body weight had fallen to that of an age-matched group of lean Zucker rats. The rate of weight loss was twice as fast in the VLCD group. Daily energy expenditure and resting metabolic rate was depressed equally (by 55-60 per cent) in both groups. The percentage of fat and fat-free mass of VLCD rats was unchanged by weight loss, but fat (per cent) was increased and fat-free mass (per cent) decreased in LCD rats. It is concluded that the depression in metabolic rate and changes in body composition induced by severe energy restriction are no greater, or even less than that produced by more modest energy restriction.

Adipose Tissue↗
PubMed1988

Thermogenic effects of thyrotrophin-releasing hormone and its analogues in the rat.

Acute or chronic injection of RX 77,368 (a TRH analogue; 1 mg/kg s.c.) stimulated oxygen consumption (VO2) and brown adipose tissue activity in the rat, and decreased weight gain. Other TRH analogues (CG 3509, RGH 2202) and TRH itself also stimulated VO2. These thermogenic actions are probably mediated centrally by stimulation of sympathetic outflow to brown fat.

Adipose Tissue, Brown↗
PubMed1988

Opposing effects of activation of central GABAA and GABAB receptors on brown fat thermogenesis in the rat.

Baclofen (a GABAB agonist) stimulates body temperature, metabolic rate and brown adipose tissue (BAT) in the rat through a central action, but no effects of gamma-aminobutyric acid (GABA) itself on these parameters were observed. In the present study, it was found that the central effects of (+/-)baclofen (0.5-2.0 micrograms injection i.c.v.) on the temperature (1.2 degrees C increase) and metabolic rate (44-76% increase) of brown adipose tissue were inhibited by previous treatment with the GABAA agonist, muscimol (0.05 micrograms). Injection of GABA alone (12 micrograms) did not significantly affect these parameters, but in the presence of the GABAA antagonist bicuculline (2.5 micrograms), GABA significantly increased the temperature (0.3 degrees C) and oxygen consumption (22%) of brown fat. (-)Baclofen was found to be approximately 50-times more effective in stimulating the temperature of brown adipose tissue than (+/-)baclofen. The results indicate that activation of central GABAB receptors stimulates the activity and hence metabolic rate of brown adipose tissue. However, activation of the GABAA receptors opposes the effects of GABAB stimulation on the thermogenesis of brown fat.

Adipose Tissue, Brown↗
PubMed1988

Chronic inhibition of GABA transaminase results in activation of thermogenesis and brown fat in the rat.

1. Oral administration of the GABA transaminase inhibitor ethanolamine-O-sulphate (EOS, 5 mg/ml in drinking water) to rats for 14 days suppressed food intake by 24%, but reduced weight gain by over 35%. 2. Thus, feed efficiency (g gain/MJ eaten) was decreased by over 15% in EOS-treated rats, suggesting that there had been an increase in metabolic rate. 3. The thermogenic response (rise in oxygen consumption, VO2) to injection of noradrenaline was enhanced by 50% and the thermogenic activity of brown adipose tissue (BAT, assessed from mitochondrial GDP-binding) was increased by 38% in EOS-treated rats. 4. Injection of baclofen (a GABAB agonist, 0.5 mg/kg s.c.) stimulated VO2 in both groups, with a significantly greater response in EOS treated rats, and this was enhanced by bicuculline (GABAA antagonist, 0.5 g/kg s.c.) in control rats and attenuated by muscimol (GABAA agonist, 0.5 mg/kg s.c.) in control and EOS-treated rats. 5. The data indicate that increasing brain GABA concentrations with EOS results in lower levels of metabolic efficiency and increases in thermogenesis.

4-Aminobutyrate Transaminase↗
PubMed1988

Changes in body composition, brown adipose tissue activity and thermogenic capacity in BN/BiRij rats undergoing senescence.

Metabolic rate, thermogenesis, brown adipose tissue (BAT) activity, and body composition were followed in ageing rats (female BN/BiRij) at 3 to 35.5 months of age. Colonic temperatures were similar in rats at 3 to 23 months of age (37.1-37.6 degrees C), but significantly reduced (36.3 degrees C) in those aged 36 months. Resting oxygen consumption (VO2), corrected for body size, was comparable in all groups, but the thermogenic response to noradrenaline was significantly reduced with age. BAT mass was unaffected by age, but brown fat protein content, specific mitochondrial cytochrome oxidase activity, and thermogenic activity (assessed from mitochondrial purine nucleotide binding) all declined markedly with age. Carcass analysis revealed a fall in body protein in very old (35.5 month) rats, but body fat content increased up to 23 months of age and thereafter declined.

Adipose Tissue, Brown↗
PubMed1988

Increased body-weight gain and body protein in castrated and adrenalectomized rats treated with clenbuterol.

1. Daily injection of the beta 2-adrenergic agonist clenbuterol (1 mg/kg body-weight) increased weight gain by 12% in young (35 d) male rats and by 18% in castrated rats, but had no effect on energy intake, expenditure or efficiency in either group. 2. Body fat content was not affected by clenbuterol or castration, but water and protein content were significantly increased by clenbuterol treatment in both intact and castrated rats. The ratio, body protein: fat was increased by 13 and 16% in these two groups compared with their respective, untreated controls. 3. Bilateral surgical adrenalectomy (ADX) of young (45 d) male rats significantly reduced body-weight, and energy intake, expenditure and efficiency. Carcass energy and fat contents were also reduced in ADX rats compared with age-matched controls. 4. Clenbuterol injections stimulated weight gain (% increase:intact 15, ADX 35), and increased body protein content (% increase:intact 12, ADX 8) and the ratio, carcass protein:fat (% increase:intact 34, ADX 23). 5. These findings demonstrate that the effects of clenbuterol on body-weight gain and composition in male rats occur in the absence of either gonadal or adrenal hormones. Together with other studies, these results provide further evidence to suggest that clenbuterol probably exerts its effects by a direct action on lean body mass.

Adrenalectomy↗
PubMed1988

The cafeteria diet as a tool for studies of thermogenesis.

The cafeteria diet involves feeding experimental animals a choice of palatable human food items to stimulate energy intake, and has been used extensively to study diet-induced thermogenesis. In a recent commentary Moore has argued that this feeding regime is inappropriate for such studies because the nutrient composition cannot be controlled, many of the effects seen are due to protein or nutrient deficiency and accurate measurements of energy intake are difficult to achieve. We argue that all of these criticisms can be overcome by careful use of the feeding regime and well-controlled experiments. Gross nutrient composition of cafeteria diets can be modified over a wide range, and such studies demonstrate that the effects of protein deficiency can be clearly dissociated from those of hyperphagia. There is no experimental evidence for nutritional deficiency in cafeteria-fed animals even over very long periods of time. Furthermore, the alternatives suggested by Moore, i.e., presenting sucrose solutions to drink or high fat diets, suffer the same drawbacks of altered and often uncontrolled nutrient intake and yet produce little or no increase in energy intake. Criticism of the cafeteria diet is not justified simply because of its misuse by nutritionally naive experimenters. The value and validity of this feeding regime is further supported by the enormous impact it has made on our understanding of energy balance regulation and thermogenesis.

Animals↗