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Query: UMLS:C0028754 (obesity)
 124,988 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Studies on BRL 26830A in rodents have shown that thermogenic beta-adrenoceptor agonists have potential for the therapy of obesity. BRL 26830A reduced body weight gain in ob/ob mice and fa/fa rats by reducing lipid accumulation. It had no effect on lean body mass. BRL 26830A did not reduce food intake, its anti-obesity effect being due to stimulation of energy expenditure. This thermic effect was enhanced in the obese animals by repeat dosing. BRL 26830A did not affect body weight gain in the lean counterparts of the obese animals because its thermic effect in lean animals was reduced by repeat dosing. Brown adipose tissue is an important site of BRL 26830A-induced thermogenesis. A single dose of BRL 26830A raised brown adipose tissue temperature, depleted brown adipose tissue lipid and unmasked GDP-binding sites in brown adipose tissue mitochondria. Repeat dosing caused hypertrophy of brown adipose tissue and improved cold tolerance in mice. In-vitro studies showed that the rat brown adipocyte beta-adrenoceptor does not fall into the beta 1/beta 2 classification and BRL 28410, which mediates the biological effects of BRL 26830A in vivo, selectively stimulated the brown adipocyte receptor. It is concluded that BRL 26830A achieves its anti-obesity effect by mimicking natural mechanisms involved in thermogenesis and the control of body weight.
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PMID:Treatment of obesity with thermogenic beta-adrenoceptor agonists: studies on BRL 26830A in rodents. 615 55

The concept that thermogenesis in brown adipose tissue can play a role as an energy buffer has developed during the last 5 years. The history of this development is reviewed. Control of brown adipose tissue thermogenesis resides in regions of the brain, located primarily but not exclusively in the hypothalamus, that control the activity of the sympathetic nervous system in response to diet and to environmental temperature. Brown adipose tissue mitochondria are uniquely specialized for thermogenesis, possessing a specific proton leakage mechanism that is regulated by the concentration of fatty acids in the cells of the brown adipose tissue. The level of fatty acids is in turn controlled by the lipolytic action of noradrenaline on the tissue. Sympathetic stimulation also exerts a trophic influence on brown adipose tissue. Effective thermogenesis in brown adipose tissue is associated with leanness and decreased metabolic efficiency, as in the rat rendered hyperphagic and hypermetabolic, by either cold acclimation or cafeteria feeding. Conversely, food restriction is associated with suppressed thermogenesis in brown adipose tissue and increased metabolic efficiency. Defective brown adipose tissue thermogenesis is associated with obesity in a number of different types of obese animals. In three of these (the genetically obese fa/fa Zucker rat, the mouse with hypothalamic damage induced by gold thioglucose, the rat with a surgically induced hypothalamic lesion), diet-induced thermogenesis is defective in brown adipose tissue, but cold-induced thermogenesis is normal. In another type of obese animal, the genetically obese (ob/ob) mouse, control of brown adipose tissue is defective. Studies of this control are complicated by the frequency of torpor in the fed state.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Brown adipose tissue thermogenesis, energy balance, and obesity. 638 75

Nonshivering thermogenesis was originally defined as a cold-induced increase in heat production not associated with the muscle activity of shivering. Recent research shows it to be a metabolic process located primarily in brown adipose tissue and controlled by the activity of the sympathetic nervous supply of this tissue. Another stimulus to sympathetic nervous activity, the ingestion of food, promotes diet-induced thermogenesis in brown adipose tissue. Brown adipose tissue grows and regresses in accordance with the extent to which it is stimulated, either by cold or by diet, and the capacity of the animal for cold-induced nonshivering thermogenesis and diet-induced thermogenesis increases or decreases accordingly. In certain hibernators another stimulus, photoperiod, promotes growth or regression of brown adipose tissue. The neural regulation of thermogenesis in brown adipose tissue is thus not only part of the central control mechanisms involved in thermoregulation but also part of those involved in the regulation of energy balance. In hibernators , such as the hamster, the neural regulation of thermogenesis in brown adipose tissue includes, in addition, central components that control the function of brown adipose tissue during entry into and arousal from hibernation and pineal or melatonin-related components that control its growth in response to photoperiod. In animals which become intermittently torpid, such as the mouse, the regulation includes in addition central components that control the function of brown adipose tissue during entry into and arousal from torpor. The central neural components involved in control of thermoregulation are better understood than are those involved in the regulation of energy balance. Studies of animal with hypothalamic obesity indicate that the control of diet-induced thermogenesis in brown adipose tissue requires the participation of the ventromedial region of the hypothalamus whereas the control of cold-induced nonshivering thermogenesis does not. The importance of comparative studies in different species is emphasized since any neural model for the control of brown adipose tissue thermogenesis is likely to apply in detail only to the species for which it was developed.
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PMID:Nonshivering thermogenesis. 672 94

Brown adipose tissue, a well known effector of regulatory thermogenesis found in mammals, is unique in its ability to steadily increase its heat production several fold for very long periods of time. It constitutes a shunt of energy flow between food intake and heat dissipation, it is activated through its sympathetic nerve supply. There are evidence in the rat, that brown adipose tissue is activated following overfeeding, thus decreasing food efficiency and determining resistance to obesity. Genetically obese (ob/ob) mice fed and kept at 22 degrees C lack the possibility of activating their brown fat energy shunt; they are known to be poorly resistant to cold stress despite their large insulation. This is taken as a further circumstantial evidence of an overlap in thermal and food efficiency regulatory systems in rodents through sympathetically controlled brown fast as a common effector.
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PMID:Is there a sympathetic regulation of the efficiency of energy utilization? 701 32

The objective of this work was to evaluate how obesity would influence the changes in brown fat (BAT) thermogenic capacity during fasting-refeeding. Mice fed either chow or chow + high-fat supplement for 6 wk had body weights of 34 +/- 1 and 43 +/- 1 g, respectively. They were fasted for 48 h followed by ad libitum refeeding for up to 5 days. Loss of carcass fat was similar between food-deprived mice previously fed chow or chow + high-fat supplement. However, even after a 48-h fast, obese mice still had a carcass fat content much greater than that of chow-fed mice. Brown fat atrophy caused by food deprivation was characterized by reductions in tissue weight, fat, mitochondrial proteins and uncoupling protein (UCP), without change in tissue DNA. Obesity did not alter the rate or extent of brown fat atrophy. Upon refeeding 48-h-fasted lean and obese mice, there was recovery of BAT thermogenic capacity that was similar between the two groups. In chow-fed mice, an intact neural input was essential for recovery of BAT thermogenic capacity during refeeding. These results indicate that food deprivation triggers an immediate adaptive response in mice previously fed chow or chow + a high-fat supplement and that reduction in brown fat thermogenic capacity during fasting and its recovery during refeeding appear little affected by the size of the animal energy reserves.
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PMID:Changes in brown adipose tissue composition during fasting and refeeding of diet-induced obese mice. 802 46

After three decades of physiological research, the precise nature of the genetic lesion in Zucker fatty (fa/fa) rats remains unknown. Several methods have been used to identify preobese rats to detect the earliest phenotypic effects of the fa mutation. Most of these methods have used phenotypic characteristics that are not reliable until the second week of life, when increased adiposity is already evident. We have used a restriction fragment length polymorphism (RFLP) for a human genomic DNA probe (VC85) that is tightly linked to the fa locus on rat chromosome 5 to genotype the F2 progeny of a Zucker (13M) x Brown Norway (BN) fa/+ F1 intercross. Sixty-four rats, comprising five litters, were killed at 5-6 wk of age. DNA was isolated either from tail at age 4-7 days (36 rats) or from organs at the time of death (28 rats). Adiposity was scored using inguinal fat pad weight as a percentage of body weight. RFLP analysis was > 99% accurate in identifying obese (fa/fa) rats. This molecular genetic method can be used to genotype fatty rats from an appropriate genetic cross at any age, even prenatally. Moreover, this method can distinguish heterozygous from homozygous littermates, enabling an analysis of gene dosage effects.
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PMID:A molecular genetic method for genotyping fatty (fa/fa) rats. 809 75

Brown adipose tissue, because of its capacity for uncoupled mitochondrial respiration, has been implicated as an important site of facultative energy expenditure. This has led to speculation that this tissue normally functions to prevent obesity. Attempts to ablate or denervate brown adipose tissue surgically have been uninformative because it exists in diffuse depots and has substantial capacity for regeneration and hypertrophy. Here we have used a transgenic toxigene approach to create two lines of transgenic mice with primary deficiency of brown adipose tissue. At 16 days, both lines have decreased brown fat and obesity. In one line, brown fat subsequently regenerates and obesity resolves. In the other line, the deficiency persists and obesity, with its morbid complications, advances. Obesity develops in the absence of hyperphagia, indicating that brown fat deficient mice have increased metabolic efficiency. As obesity progresses, transgenic animals develop hyperphagia. This study supports a critical role for brown adipose tissue in the nutritional homeostasis of mice.
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PMID:Development of obesity in transgenic mice after genetic ablation of brown adipose tissue. 826 93

Corticotropin-releasing factor (CRF) appears to regulate several physiological systems that display prominent abnormalities in Zucker fatty (fa/fa) rats, including the hypothalamic-pituitary-adrenal axis, the autonomic nervous system, and feeding behavior. Moreover, central administration of CRF ameliorates the obese phenotype. In light of these observations, the gene for CRF is a plausible candidate for the defective gene in the Zucker fatty rat. We report here the use of molecular genetic linkage analysis to test the hypothesis that fa is a mutant allele of the CRF gene. A restriction fragment length polymorphism for CRF between Zucker (13M) and Brown Norway (BN) DNA allowed us to examine segregation of 13M and BN CRF alleles relative to fa in 58 obese (fa/fa) F2 progeny of a 13MBN fa/+F1 intercross. If fa = CRF, all animals homozygous for the fatty mutation should be homozygous for the 13M CRF allele. However, only 10/58 fa/fa animals were homozygous for the 13M CRF allele, indicating that fa and CRF are not allelic. Thus, although CRF may be important in the physiology of Zucker rat obesity, fa is not a CRF mutation. Using a mouse C57BL/6J Spretus F1 x C57BL DBA/2J F1 intercross, we were able to demonstrate that the mouse CRF gene is linked to the carbonic anhydrase II (Car-2) gene on mouse chromosome 3, in a region of synteny-homology with rat chromosome 2. Thus the rat CRF gene is probably located on chromosome 2.
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PMID:The Zucker fatty (fa) gene is not a mutation of corticotropin-releasing factor. 843 Aug 72

In seeking an animal model of age-associated changes in the male reproductive tract, we examined the effects of age on the health and testicular steroidogenic activity of the Brown Norway rat, with comparisons made to the Sprague-Dawley rat. When perfused in vitro under conditions of maximally stimulating luteinizing hormone significant age-associated reductions were seen in testosterone production by testes of Sprague-Dawley rats of 21-24 months of age and by testes of Brown Norway rats of 18-30 months of age. Decreases in the capacity of the testes to produce testosterone were reflected in age-associated decreases in both serum testosterone and in testosterone concentration within the seminiferous tubule fluid. In contrast to the Sprague-Dawley rat, changes in steroidogenic activity in the Brown Norway rat were not accompanied by the occurrence of pituitary adenomas, obesity, or testicular tumors. This along with its longevity, make the Brown Norway strain a highly promising model for testicular aging.
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PMID:Testicular steroidogenesis in the aging brown Norway rat. 851 17

Brown adipose tissue (BAT) is involved in the control of energy balance and has been demonstrated to be activated through beta 3-adrenoceptor (beta 3-AR) occupation in rodents. The ability to specifically activate energy expenditure via this receptor is of great interest for the treatment of obesity. Nevertheless, the extent of BAT and the presence of a functional beta 3-AR in humans are now debated, and this situation is difficult to clarify for evident practical and ethical reasons. We investigated the occurrence of brown adipocytes in fat deposits of prepubertal baboons using antibodies raised against uncoupling protein (UCP) in Western blotting and immunocytology experiments. UCP was detected in all types of fat pads studied and was revealed in multilocular cells. Pericardiac and axillary adipose tissues displayed large amounts of UCP and can be assimilated to typical BAT. Most of the other pads looked like white adipose tissue, but exhibited areas with clusters of brown adipocytes and, thus, can be assimilated to the convertible adipose tissue as previously described in rodents. The presence of beta 3-ARs was evaluated by both beta 2-agonist-stimulated lipolysis and messenger ribonucleic acid (mRNA) expression studies. There was no significant lipolytic effect of any of the beta 3-AR agonists tested (SR 58611A, BRL 37344, CGP 12177, or CL 316243) in either white or brown tissues. PCR analysis demonstrated that beta 3-AR mRNA expression is not related to the UCP content of fat pads and that beta 3-AR expression is low. This study demonstrates the presence of great proportions of brown adipocytes in adipose tissue and the heterogeneity of the fat pads in baboons. The lack of a metabolic effect of beta 3-agonists combined with the weak expression of beta 3-AR mRNAs raise the question of the role of beta 3-ARs in adipose tissues of primates.
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PMID:Evidence for numerous brown adipocytes lacking functional beta 3-adrenoceptors in fat pads from nonhuman primates. 855 Jul 79


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