Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0028754 (obesity)
 124,988 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Thermogenesis in brown adipose tissue is now regarded as being a major component in the normal energy expenditure of laboratory rodents, and variations in the level of thermogenesis in the tissue are important in the regulation of energy balance. Defective thermogenic responses to diet or to cold have been shown to be central to the development of obesity in various rodent models. The quantitative importance of brown adipose tissue thermogenesis to energy expenditure in species other than rodents has not been established, but it is clear that the tissue is present in a wide range of mammals. In particular, active brown adipose tissue has now been identified in adult humans, as well as in newborn infants.
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PMID:Energy expenditure and thermogenesis: animal studies on brown adipose tissue. 222 15

Ingestion of carbohydrate results in a diphasic activation of the sympathoadrenal system. One component is an insulin-mediated activation of the sympathetic nervous system (SNS). This activation is partly a haemodynamic reflex, but it may cause a weak thermogenic effect via beta 1-adrenoceptors in white adipose tissue, the liver and the heart. The second thermogenic component of carbohydrate occurs later when the blood glucose concentration decreases towards baseline levels. This elicits an increased secretion of adrenaline from the adrenal medulla, and the circulating level exceeds the physiological threshold for thermogenic effect. The target is mainly skeletal muscle where thermogenesis is stimulated via beta 2-adrenoceptors. Also the basal metabolic rate and the thermogenic responses to cold and heat exposure, mental stress and exercise, have facultative components. Inhibition of facultative thermogenesis by beta-blockers such as propranolol, diminishes the daily energy expenditure and promotes weight gain and obesity. Although thermogenesis mediated by the sympathoadrenal system accounts for only a small part of the daily energy expenditure, it is sufficient to explain the positive energy balance and weight gain reported in patients receiving treatment with beta-adrenoceptor blocking agents.
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PMID:Effects of nutrient intake on sympathoadrenal activity and thermogenic mechanisms. 225 41

The anti-obesity drug fenfluramine, promotes loss of weight by reducing food intake; however, there is controversy as to whether the drug can also elevate expenditure of energy. Resting consumption of oxygen (VO2) was measured in conscious rats to determine whether the injection of fenfluramine increased metabolic rate and whether prior fasting, or ambient temperature altered the response. Regardless of whether the rats were fed or had been fasted for 22 hr, in a thermoneutral environment (28 degrees C), the intraperitoneal injection of dl-fenfluramine (20 mg/kg) caused a raised oxygen consumption. This elevation was sustained to the end of the 60-min period of measurement after the injection, at which point the colonic temperature was found to be increased. This metabolic response to fenfluramine was largely attenuated when the drug was administered at 23 degrees C, and the colonic temperature of the rats was decreased by 60 min after the injection. At 4 degrees C, the injection of fenfluramine inhibited thermogenesis against cold, the oxygen consumption fell and the rats exhibited hypothermia. It was concluded that fenfluramine can increase the metabolic rate, but that this effect is not conditional on associated food intake, as has been reported. Rather, the ambient temperature governs whether stimulation or inhibition of thermogenesis will be evoked. These metabolic effects of fenfluramine explain, in part, its divergent effects on body temperature, reported previously.
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PMID:Ambient temperature modulation of fenfluramine-induced thermogenesis in the rat. 232 33

To test whether or not the onset of obesity in fatty (fa/fa) Zucker rats is caused by decreased thermoregulatory thermogenesis, pups were artificially reared above their lower critical temperature from 3 or 4 days of age. Littermates were continuously fed identical amounts of synthetic rat milk while body temperature (Tc) and oxygen consumption rate (VO2) were continuously recorded. When the daily mean Tc of all pups was held greater than 37 degrees C, neither Tc nor VO2 differed between fa/fa and genetically lean (Fa/-) pups during the first 2 wk of life. Tc and VO2 were significantly elevated in Fa/- pups during the third postnatal week. At both 16 and 21 days of age, fa/fa pups were identified by their low Tc during a brief cold exposure. Body fat and fat-free dry mass of fa/fa and Fa/- littermates differed at 21 but not at 16 days of age. The excess energy deposited as fat was partly derived from decreased nonthermoregulatory energy expenditure and decreased synthesis of lean body mass. Calculations support the speculation that a greater extraction of energy from the synthetic diet additionally supports the excess fat deposition. Decreased thermoregulatory thermogenesis and excess fat storage appear to be secondary and independent consequences of the primary genetic lesion.
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PMID:Defective thermoregulatory thermogenesis does not cause onset of obesity in Zucker rats. 237 52

The effect of CGP-12177, originally developed as a radioligand with antagonist properties for binding studies of beta-adrenergic receptors, was investigated in brown adipose tissue. Contrary to expectations, CGP-12177 showed clear agonist properties in experiments with hamster brown-fat cells, with a maximal effect in stimulating oxygen consumption similar to that of the physiological stimulator noradrenaline, and also with a potency similar to that of noradrenaline [EC50 (50% effective concn.) approx. 70 nM]. This value could be contrasted with the very high affinity of CGP-12177 (KD about 1 nM) for ligand-binding sites on the cells. It is therefore suggested that the high-affinity binding site may not be the one that mediates the CGP-12177-stimulated thermogenesis in isolated cells. Also, when injected into cold-adapted rats, CGP-12177 stimulated non-shivering thermogenesis similarly to noradrenaline. This observation, in conjunction with the reported low general sympathomimetic effect of CGP-12177, may indicate that CGP-12177 could be of interest for the development of anti-obesity drugs.
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PMID:The beta-adrenergic radioligand [3H]CGP-12177, generally classified as an antagonist, is a thermogenic agonist in brown adipose tissue. 257 May 69

Obligatory thermogenesis is a necessary accompaniment of all metabolic processes involved in maintenance of the body in the living state, and occurs in all organs. It includes energy expenditure involved in ingesting, digesting, and processing food (thermic effect of food (TEF]. At certain life stages extra energy expenditure for growth, pregnancy, or lactation would also be obligatory. Facultative thermogenesis is superimposed on obligatory thermogenesis and can be rapidly switched on and rapidly suppressed by the nervous system. Facultative thermogenesis is important in both thermal balance, in which control of thermoregulatory thermogenesis (shivering in muscle, nonshivering in brown adipose tissue (BAT] balances neural control of heat loss mechanisms, and in energy balance, in which control of facultative thermogenesis (exercise-induced in muscle, diet-induced thermogenesis (DIT) in BAT) balances control of energy intake. Thermal balance (i.e., body temperature) is much more stringently controlled than energy balance (i.e., body energy stores). Reduced energy expenditure for thermogenesis is important in two types of obesity in laboratory animals. In the first type, deficient DIT in BAT is a prominent feature of altered energy balance. It may or may not be associated with hyperphagia. In a second type, reduced cold-induced thermogenesis in BAT as well as in other organs is a prominent feature of altered thermal balance. This in turn results in altered energy balance and obesity, exacerbated in some examples by hyperphagia. In some of the hyperphagic obese animals it is likely that the exaggerated obligatory thermic effect of food so alters thermal balance that BAT thermogenesis is suppressed. In all obese animals, deficient hypothalamic control of facultative thermogenesis and (or) food intake is implicated.
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PMID:Role of thermogenesis in the regulation of energy balance in relation to obesity. 266 32

A management programme is described for a small colony of Obese strain (OS) chickens afflicted with spontaneous hereditary thyroiditis. Animals of this White Leghorn line are used as an animal model for Hashimoto's thyroiditis of man to study possible mechanisms of autoimmunity in general and organ-specific autoimmune diseases in particular. Due to the severe mononuclear cell infiltration of the thyroid glands, OS chickens show symptoms of hypothyroidism, including small body size, subcutaneous and abdominal fat deposits, long silky feathers, small combs and wattles, cold sensitivity, low fertility and poor hatchability. Successful breeding of this line, especially in a small population, can therefore be done only if rigid precautions are taken in aspects of animal care. The selection of breeding stock, the principal requirements for adequate housing and food, the artificial insemination procedure, and recommendations for collecting and incubating chicken eggs are reported in detail. Precautions necessary during the incubation of fertilized eggs, and fertility and hatchability are reported. During the hatching period several specific features must be considered. The important role of staff involved in a small chicken breeding unit is emphasized.
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PMID:Housing, breeding and selecting chickens of the Obese strain (OS) with spontaneous autoimmune thyroiditis. 281 Dec 74

Brown adipose tissue (BAT) thermogenesis was assessed by measuring mitochondrial guanosine diphosphate (GDP) binding, cytochrome oxidase activity and oxygen consumption in ovariectomized (OVX) and sham-operated rats. The food intake and body weight of OVX rats increased more than those of controls and OVX rats became obese. Mitochondrial GDP binding, as an indicator of thermogenic activity, cytochrome oxidase activity, as a marker of mitochondrial abundance, and mitochondrial respiration of BAT in OVX rats were significantly reduced compared with those in controls. And, also, even when OVX rats were restricted in food intake (pair-gained) to produce comparable changes in body weight with sham-controls, or matched in food intake (pair-fed) with sham-controls, these parameters in both pair-gained and pair-fed OVX groups were decreased markedly compared to those in sham-controls. As expected, body weight in pair-fed OVX rats increased significantly more than that in sham-controls. In response to cold exposure, these parameters of OVX rats increased as much as those of controls did. These results suggest that reduced brown adipose tissue thermogenesis might be one of the important factors that are responsible for the development of obesity after OVX.
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PMID:Reduced brown adipose tissue thermogenesis of obese rats after ovariectomy. 285 Sep 6

Mice treated with glutamate in the neonatal period are known to develop into stunted obese adults, despite hypophagia. Our objective was to find out whether brown adipose tissue (BAT) thermogenic function might be abnormal in the glutamate-obese mouse. At 10 wk of age, group-housed glutamate-obese mice exhibited nocturnal and early diurnal torpor, i.e., they thermoregulated at a lower than normal body temperature. When exposed to 4 degrees C, they died in hypothermia within 24 h. They could adapt to living at 14 degrees C for up to 1 wk but failed to adjust their food intake sufficiently to maintain their body weight. Their fat stores were, nevertheless, conserved. BAT was present in increased amounts in glutamate-obese mice. Its thermogenic activity (as assessed by the level of mitochondrial GDP binding) was normal (male mice) or reduced (female mice). A normal thermogenic responsiveness of BAT to cold occurred. The thermogenic response of BAT to a cafeteria diet was normal (male mice) or reduced (female mice). Serum corticosterone concentration was increased in both male and female glutamate-treated mice particularly in the cold. We conclude that the high metabolic efficiency and obesity of the glutamate-obese mouse are principally a consequence of its maintenance of a hypothermic torpid state for more than 50% of the time. An additional deficit in energy expenditure in female, but not male, glutamate-obese mice is associated with suppressed responsiveness of the thermogenic function of BAT to diet and may account for the greater degree of obesity in female than in male glutamate-treated mice.
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PMID:Brown adipose tissue thermogenesis, torpor, and obesity of glutamate-treated mice. 287 42

The hyperphagia and obesity induced by ventromedial hypothalamic (VMH) electrolytic lesions in female rats were associated with a 70-94% decrease in the level of beta-endorphin (beta-E) in the hypothalamus and other regions of brain, but not in the pituitary. Dynorphin (Dyn) and methionine-enkephalin (ME) levels were also decreased. Rats with VMH lesions were less sensitive to the inhibitory effect of naloxone on their food-intake. Mice injected with gold thioglucose (GTG) also showed a decrease in the hypothalamic content of beta-E and Dyn and exhibited 30% less analgesia compared to control mice after cold swim stress.
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PMID:Effect of electrolytic and chemical ventromedial hypothalamic lesions on food intake, body weight, analgesia and the CNS opioid peptides in rats and mice. 289 79


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