Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0155339 (Brown)
 12,436 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

BRL 26830A, (R*, R*)-(+/-)-methyl 4-[2-[(2-hydroxy-2-phenylethyl) amino] propyl]-benzoate, (E)-2-butenedioate (2:1) salt, is a new antihyperglycemic agent orally active in obese-hyperglycemic animal models. In C57Bl/6 ob/ob mice, BRL 26830A (1 mg/kg) given daily for periods of 14 d-6 weeks produced a marked improvement in glucose tolerance and a reduction in the fasting plasma insulin concentration. Adipocytes prepared from treated mice showed improved insulin responsiveness. In Zucker fa/fa rats, treatment with BRL 26830A (2.9 mg/kg/d for 23 d) produced improvements in both glucose tolerance and whole animal insulin sensitivity, as assessed by rate of fall of blood glucose in response to an intravenous dose of insulin. In C57Bl/KSJ db/db mice, BRL 26830A (admixed with food at 50 mg/kg diet) decreased blood glucose to values similar to those in lean mice. At the end of a 10-week treatment, BRL 26830A-treated mice had a higher plasma and pancreatic insulin content than the untreated db/db mice. In normoglycaemic rats and mice, BRL 26830A increases the plasma insulin concentration and increases glucose disposal. However, in most circumstances, there is a counteracting increase in endogenous glucose synthesis and, therefore, no change in blood glucose occurs. Improvements in glucose tolerance occur in 24-h fasted rats and mice. BRL 26830A has thermogenic activity and it is suggested that this might be linked to increased glucose utilization. Brown adipose tissue (BAT) of C57Bl/KSJ db/db mice has a reduced maximum glycolytic capacity relative to lean littermates. Treatment with BRL 26830A increased the glycolytic capacity 10-fold.
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PMID:Effects of novel beta-adrenoceptor agonists on carbohydrate metabolism: relevance for the treatment of non-insulin-dependent diabetes. 615 58

Brown adipose cells are heat-producing cells through non-shivering thermogenesis by intramitochondrial "thermogenin". This specific protein is a marker for their cellular differentiation. It has long been known that cultured brown adipose cells in monolayer rapidly lose the thermogenin bioactivity. In this study, we cultured brown adipose cells in three-dimensional type I collagen gel matrix. Under this culture condition, they were able to survive, and differentiated morphologically and functionally for a long period of time, especially exhibited the characteristic immunohistochemical activity of thermogenin. These findings suggest that brown adipose cells differentiate in type I collagen gel. In this condition, cholera toxin or BRL 37344, one of beta 3-adrenoceptor agonists, specifically stimulated the brown adipose cells.
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PMID:Differentiation of brown adipose cells in three-dimensional collagen gel culture. 851 19

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

We have recently shown that injection of the hypothalamic peptide cocaine and amphetamine regulated transcript (CART) into discrete hypothalamic nuclei stimulates food intake. This stimulation was particularly marked in the arcuate nucleus. Here we show that twice daily intra-arcuate injection of 0.2 nmole CART peptide for 7 days was associated with a 60% higher daytime food intake, an 85% higher thermogenic response to the beta3 agonist BRL 35135, and a 60% increase in brown adipose tissue UCP-1 mRNA. In a separate study, using stereotactically targeted gene transfer, a CART transgene was delivered by using polyethylenimine to the arcuate nucleus of adult rats. Food intake was increased significantly during ad libitum feeding and following periods of food withdrawal and food restriction in CART over-expressing animals. CART over-expressing animals lost 12% more weight than controls following a 24-h fast. Brown adipose tissue uncoupling protein-1 (UCP-1) mRNA levels (collected Day 25) were 80% higher in CART over-expressing animals. Finally, by using quantitative in situ hybridization, we found that chronic cold exposure (20 days at 4oC) increased arcuate nucleus CART mRNA by 124%. Together with the orexigenic and thermogenic effects of CART, this finding suggests a role for arcuate nucleus CART in cold adaptation.
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PMID:A role for arcuate cocaine and amphetamine-regulated transcript in hyperphagia, thermogenesis, and cold adaptation. 1295 77

Tomato yellow leaf curl virus (TYLCV) is a begomovirus (Geminiviridae) that causes a serious disease of tomato throughout the world. In 1997, the strain from Israel of TYLCV (TYLCV-IS) was found infecting tomatoes in Florida for the first time in the United States (1). During late spring of 2000, approximately 90% of the tomato plants (Lycopersicon esculentum) in a farm near New Orleans exhibited severe stunting, leaf cupping, and chlorosis. Symptoms were similar to those caused by TYLCV. Whiteflies (Bemisia tabaci biotype B) were present in the field but in relatively low numbers. The effect on yield reduction varied from negligible (late infections) to 100% (early infections). Six selected plants showing symptoms were assayed by polymerase chain reaction (PCR) using begomovirus-specific primers. Capsicum frutescens infected with an isolate of Texas pepper virus from Costa Rica was used as positive control. DNA was extracted using Plant DNAzol Reagent (GIBCO BRL). PCR was conducted using degenerate primers AV494/AC1048 that amplify the core coat protein region of most begomoviruses (2). PCR yielded a DNA fragment of approximately 550 bp, suggesting that a begomovirus was associated with the disease. The amplified DNA of one field isolate was cloned and the nucleotide (nt) sequence determined. Sequence comparisons with other begomoviruses in the GenBank Database indicated that the Louisiana isolate shared 100% nt identity with TYLCV-IS (GenBank Accession X76319). Successful transmission (100%) to Bonny Best tomato were obtained with four groups of 10 whiteflies each (B. tabaci biotype B) that fed on TYLCV-IS infected tomato plants. Acquisition and transmission feedings were for 2 days. In all cases, the virus was diagnosed by the ability to reproduce typical TYLCV-like symptoms in tomato and PCR. The virus was also successfully graft-transmitted to tomato cv. Bonny Best, Nicotiana benthamiana, and tomatillo (Physalis ixocarpa) using scions from tomato plants infected with a whitefly transmitted virus isolate. This is the first report of TYLCV-IS in Louisiana. References: (1) J. E. Polston et al. Plant Dis. 83:984-988, 1999. (2) S. D. Wyatt and J. K. Brown. Phytopathology 86:1288-1293, 1996.
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PMID:First Report of Tomato yellow leaf curl virus in Louisiana. 3083 58