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

Previous studies showed that atrophy of brown adipose tissue (BAT) of capsaicin-desensitized rats occurs rapidly and persists for up to 28 days. The rats do not, however, become any more obese than control rats, despite the frequent association of atrophied BAT with obesity. The objective of the present study was to assess longer-term effects of capsaicin desensitization on BAT and on energy balance. Rats were studied at 2.5, 3.5, and 8 mo after treatment. Major effects at 8 mo, mostly seen to a lesser extent at 3.5 mo but not at 2.5 mo, were a marked reduction in body weight that was largely attributable to a reduction in body fat but also to some stunting of growth and an atrophy or lack of growth of BAT (reduced weight and content of protein, DNA, cytochrome oxidase, and uncoupling protein). Resting metabolic rates and food intake at 8 mo were reduced in proportion to the smaller body size. We suggest that the lack of trophic influence of sensory neuropeptides on BAT proposed previously may extend to other organs, including white adipose tissue, and contribute to the reduced adiposity and the smaller body size of capsaicin-desensitized rats.
 ...
PMID:Long-term decrease in body fat and in brown adipose tissue in capsaicin-desensitized rats. 131 15

The regulation of energy metabolism in obesity may differ from normal condition in several respects. The synthesis of lipids may be enhanced due to a greater production of insulin, estrogens and cortisol and to a lack of dehydroepiandrosterone. Lipolysis is reduced in obese subjects by a decreased secretion of catecholamines, growth hormone, adipsin and cachectin. Inadequate intake of food and stress modify the T3/rT3 ratio. Oxidative phosphorylation and the production of ATP is modified, thermogenesis decreases due to a reduced synthesis of thermogenin. A decreased activity of substrate cycles and of the Na-K ATPase, is expected. Most of these disorders are normalized in post-obese patients. Many common drugs interfere with energy metabolism, namely those used in psychiatry and all hormones and their antagonists mentioned above and used for a long time. Obesity should not be considered as a simple result of overeating and lack of physical activity.
 ...
PMID:[Energy metabolism in obesity]. 158 28

Injections of 6-hydroxydopamine in mouse neonates caused extensive and long lasting damage to the sympathetic nervous system and impaired brown fat development. Brown adipose tissue (BAT) thermogenic capacity of sympathectomized mice (up to 120 days old) was reduced because of marked reductions in the tissue mitochondrial protein content and the mitochondrial concentration of uncoupling protein, as assessed by [3H]GDP binding and immunoassay. Neonatal sympathectomy did not affect BAT DNA content. Sympathectomized mice also had reduced epinephrine-stimulated rates of oxygen consumption. BAT of sympathectomized mice failed to respond by increases in [3H]GDP binding to isolated mitochondria and uncoupling protein concentration when animals were offered a palatable high-fat dietary supplement that increased calorie intake of both normal and sympathectomized mice. The high-fat diet caused increases in body weight, carcass fat, and gonadal white fat pad weights in sympathectomized animals that were similar to those of control mice. These results show that inactivation of BAT metabolism did not accentuate the development of obesity caused by a dietary supplement rich in fat and suggest that stimulation of BAT metabolism was not very effective in counteracting the obesity-inducing effect of this diet.
 ...
PMID:Effects of neonatal sympathectomy on brown fat development and susceptibility to high fat diet induced obesity in mice. 180 59

Besides having a metabolic and insulatory-supporting function, adipose tissue in endotherms also performs a thermogenic function. Thermogenic adipocytes contain specific UC-mitochondria with uncoupling protein (UCP) and produce heat. Thermogenic adipose tissue has two forms: brown adipose tissue (BAT) and convertible adipose tissue (CAT). Brown adipocytes have UC-mitochondria and express UCP throughout the entire life of small rodents, chiropterans, and insectivores. However, in other endotherms and in humans CAT participates as thermogenic tissue only during early postnatal period. Both BAT and CAT start to develop in utero, although in some animals (hamsters, marsupials) or in some particular areas (thoraco-periaortal and medio-perirenal areas in rats) development of thermogenic adipose tissue starts after birth. Postnatal development of BAT in small endotherms is characterized by quantitative changes (the amount of UC-mitochondria, UCP, and lipids). Postnatal development of CAT causes qualitative changes during which UC-mitochondria in convertible adipocytes are replaced by common, nonthermogenic C-mitochondria; vascularization of adipocytes drops to a low level and, with lipid accumulation, convertible adipocytes appear as lipid-store cells. Postnatal development of CAT can be modulated or reversed by the environmental temperature. The duration of postnatal changes varies between species; i.e., cats, rabbits and sheep, change their thermogenic form of CAT into the lipid-store form within the first postnatal month, while in humans the same process takes up to 15-20 years. In maturity all these large endotherms have CAT in lipid-store form. In light of these results, the question of participation of thermogenic adipose tissue in the regulation of human obesity needs to be answered.
 ...
PMID:Development of thermogenic adipose tissue. 181 13

The uncoupling protein (UCP) is a proton/anion transporter found in the inner mitochondrial membrane of brown adipocyte. Although UCP has not been detected in mitochondria from any other tissue, it shares structural and catalytic properties with several other mitochondrial carrier proteins. Although UCP was discovered only recently it is one of the most extensively studied mitochondrial carrier proteins. Many tools useful in research on UCP have been developed such as antibodies and cDNAs corresponding to UCP of several animal species. More recently, the mouse, rat, and human genes encoding for UCP have been isolated and sequenced. The availability of these various tools has led to several significant observations. UCP gene expression is strongly controlled at the level of transcription by signals that are activated after the stimulation of brown adipocytes by norepinephrine. The comparison of UCP gene with the genes encoding the adenine nucleotide translocator revealed the existence of structural and evolutionary homologies. Moreover, in humans the UCP gene and one form of adenine nucleotide translocator gene are located on the same chromosome. Recently, the expression of functional UCP in various heterologous systems was achieved (Xenopus oocytes, CHO cells, yeasts). These data will facilitate studies of the structure/function relationship in UCP (identification of residues involved in H+ transport, Cl- transport, nucleotide binding, mitochondrial targeting...). Another aspect of the present research on UCP is the understanding of mechanisms that control the UCP gene and the differentiated commitment of adipose precursor cells to thermogenic brown adipocytes. The multifaceted aspects of research on UCP make this protein interesting in areas of research as different as studies of ion translocating mechanisms, cellular specificity of gene transcription, control of gene expression by neuromediators, adipocyte differentiation, and the pharmacological treatment of obesity.
 ...
PMID:Molecular studies of the uncoupling protein. 186 Jun 14

Energy expenditure for thermogenesis in brown adipose tissue (BAT) serves either to maintain body temperature in the cold or to waste food energy. It has roles in thermal balance and energy balance, and when defective, is usually associated with obesity. BAT can grow or atrophy; it is usually atrophied in obese animals. Control of BAT thermogenesis and growth is by the sympathetic nervous system, with integration of signals in the hypothalamus. Sensory nerves may also be involved. Understanding the control of growth and differentiation of BAT is important for discovering how to reactivate it is obesity. Studies on control of gene expression in BAT are concentrating on thermogenically important components such as the uncoupling protein (which allows BAT mitochondria to operate in a thermogenic uncoupled mode), lipoprotein lipase (which allows BAT to compete with white adipose tissue for dietary lipid), and thyroxine 5'-deiodinase (which allows endogenous triiodothyronine generation, part of the control of differentiation and growth of BAT). Differentiation of BAT cell precursors in culture has recently been achieved. BAT is present in adult humans and some anti-obesity drugs are targeted to stimulation of BAT thermogenesis. However, extrapolation to humans of results of studies of BAT requires the development of novel approaches to the noninvasive assessment of amount and function of human BAT.
 ...
PMID:Brown adipose tissue thermogenesis: interdisciplinary studies. 219 86

Mice selected for high body weight (QL522) had increased food intake, body weight gain, and fat deposition relative to mice without weight selection (QL521). Brown adipose tissue (BAT) thermogenic capacity, as determined by the tissue content of protein, DNA, and succinate dehydrogenase and by mitochondrial uncoupling protein content was similar or slightly higher in 2- and 10-mo-old QL522 mice relative to age-matched QL521 mice. When food intake of QL522 mice was restricted to the level of QL521 mice, body weight gain and fat deposition over 28 days were then comparable to those of QL521 mice. Food restriction had no effect on BAT composition of QL522 mice. Both QL521 and QL522 mice increased calorie intake by 40-50% when offered a palatable high-fat supplement (HF), but only QL522 mice increased weight gain and fat deposition significantly. QL521 mice fed a high-fat supplement showed a significant increase in brown fat succinate dehydrogenase content, whereas QL522 mice showed significant increases in brown fat weight, protein, and succinate dehydrogenase content relative to mice fed stock diet. Nonshivering thermogenic capacity, as assessed by norepinephrine-stimulated oxygen uptake in anesthetized animals at 30 degrees C was similar between QL521 and QL522 mice eating stock diet and was significantly increased by the high-fat supplement in both strains. Thus mice selected for high body weight are very susceptible to diet-induced obesity, and we have no evidence that a reduction in brown fat thermogenic capacity contributes to the increased fat deposition of QL522 mice as they grow old or when they are offered palatable energy-dense supplements.
 ...
PMID:Weight gain and brown fat composition of mice selected for high body weight fed a high-fat diet. 231 10

The effect of a new type of antidiabetic agent, BRL 26830A, has been tested in obese mice. Since this drug increases thermogenesis, insulin receptor binding and kinase activity were studied in brown adipose tissue and skeletal muscle of mice made obese by gold thioglucose. At 1 mg.kg-1.day-1, a 3-wk treatment normalized the glycemia and increased the uncoupling protein content of brown adipose tissue. The insulin receptor number and its associated kinase activity increased only in brown adipose tissue. At 2 mg.kg-1.day-1, additional effects, i.e., a 20% reduction in body weight and a normalization of insulin receptor number both in brown adipose tissue and in skeletal muscle, were observed. All those results were obtained even though hyperinsulinemia was not corrected. At the higher drug dosage, insulin receptor kinase activity evolved in direct proportion to the receptor number in brown adipose tissue. By contrast, in skeletal muscle, the receptor kinase activity toward exogenous substrates increased more than the receptor number, suggesting that the alteration of insulin receptor kinase activity previously reported in skeletal muscle of obese mice was partly reversed by BRL 26830A. None of these parameters was modified by the drug in lean mice. These results show that, even without affecting obesity, BRL 26830A improves insulin resistance in obese mice, probably through its effect on insulin receptors. This action prevails in brown adipose tissue, supporting the idea that this tissue plays an important role in glucose homeostasis. Thermogenic drugs could thus be powerful agents for the treatment of noninsulin-dependent diabetics.
 ...
PMID:Effect of a thermogenic agent, BRL 26830A, on insulin receptors in obese mice. 284 63

A cloned cDNA sequence for the unique mitochondrial uncoupling protein of rat brown adipose tissue has been used to assay the corresponding mRNA in several situations. When thermogenesis in brown adipose tissue is stimulated (exposure of adult rats to the cold, birth) a rapid and prolonged increase in the level of uncoupling protein mRNA is observed. Such an increase can be mimicked by injection of animals with a new beta-adrenoreceptor agonist BRL 26830A. Conversely it is known that mice and rats with genetic or surgical obesity have a weakly thermogenic brown adipose tissue with a reduced norepinephrine turnover. A reduced level of uncoupling protein mRNA was measured in obese fa/fa rats 10 days or 10 weeks old and in obese rats with a lesion of the ventromedial hypothalamic area but not in obese ob/ob mice. Moreover, exposure of obese animals to cold or dosing with BRL 26830A strikingly increased the level of uncoupling protein mRNA. Measurement of the relative concentration of nascent Ucp transcripts in nuclei isolated from brown adipose tissue indicates that Ucp gene is acutely (within 15 min) regulated at the level of transcription and is controlled via activation of beta-adrenoreceptors of plasma membrane. Ucp gene transcription is decreased in obese fa/fa rats but can be fully and rapidly turned on after injection of BRL 26830A.
 ...
PMID:Expression of uncoupling protein mRNA in thermogenic or weakly thermogenic brown adipose tissue. Evidence for a rapid beta-adrenoreceptor-mediated and transcriptionally regulated step during activation of thermogenesis. 302 20

The objective was to assess the effect of a new, highly selective beta 3-adrenergic agonist, CL-316,243 (CL) (J. D. Bloom, M. D. Dutia, B. D. Johnson, A. Wissner, M. G. Burns, E. E. Largis, J. A. Dolan, and T. H. Claus., J. Med. Chem. 35: 3081, 1992), on energy balance and brown and white adipose tissues (BAT and WAT, respectively) in young rats eating a high-fat diet to induce obesity. Chronic treatment with CL increased body temperature and 24-h energy expenditure, mainly by increasing resting metabolic rate. Food intake was not altered but carcass fat was reduced. Interscapular BAT was markedly hypertrophied, with three- to fourfold increases in the content of uncoupling protein (UCP) and cytochrome oxidase. Quantitative immunoelectron microscopy of interscapular BAT of CL-treated rats showed smaller mitochondria with an unchanged total amount of UCP per mitochondrion. The relative frequency of the four major cell types in BAT (mature brown adipocytes, preadipocytes, interstitial cells, endothelial cells) was not altered. The CL-induced hypertrophy differed from that induced by chronic stimulation by endogenous norepinephrine (as in cold-adaptation) in absence of hyperplasia (there was a slightly reduced DNA content), absence of an increase in the thyroxine (T4) 5'-deiodinase activity, and absence of a selective increase in UCP concentration. WAT depots weighed less and had fewer cells (lower DNA content) in the CL-treated rats. Some multilocular adipocytes appeared in these normally almost exclusively unilocular WAT depots (mesenteric, inguinal, epididymal, retroperitoneal). We conclude that CL not only promotes BAT mitochondrial proliferation and thermogenesis and overall energy expenditure and leanness, but also retards the development of WAT hyperplasia during the early stage of diet-induced obesity.
 ...
PMID:Effect of CL-316,243, a thermogenic beta 3-agonist, on energy balance and brown and white adipose tissues in rats. 791 Apr 36


1 2 3 4 5 6 7 8 9 10 Next >>