Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0038187 (starvation)
 24,951 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Brown adipose tissue (BAT) is characterized by the existence of a unique mitochondrial protein (uncoupling protein or UCP) that uncouples oxidative phosphorylation and thus allows heat production. Its role in thermogenesis has been emphasized in recent years in response to cold stress (nonshivering thermogenesis, NST) as well as to hyperphagia (diet-induced thermogenesis, DIT). The present work was a first attempt to determine whether varying nutritional conditions could affect UCP gene expression. Total RNA was isolated from interscapular BAT and hybridized with a cDNA probe for UCP. Changes in UCP mRNA level were studied in rats fasted and refed for various periods at 23 or 28 degrees C. A 2 d fast at 23 degrees C reduced UCP mRNA level, whereas refeeding increased it. A prolonged starvation (53 h) induced an unexpected rise in UCP mRNA, which was associated with a fall in body temperature. Increasing the ambient temperature to thermoneutrality (28 degrees C) suppressed the fall in body temperature as well as the rise in UCP mRNA, which could then be characterized as a cold-induced response. Under the same environmental conditions (28 degrees C), refeeding still triggered a sharp, though transient, increase in UCP mRNA, showing that DIT was dissociated from NST.
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PMID:Effects of fasting and refeeding on the level of uncoupling protein mRNA in rat brown adipose tissue: evidence for diet-induced and cold-induced responses. 226 17

The relative stability against a decrease in adrenergic stimulation of the uncoupling protein (UCP) incorporated into different mitochondrial fractions was investigated in brown-fat-cell cultures. Cultures were initiated with undifferentiated cells from young mice and were acutely stimulated with noradrenaline at confluence (day 7). Cells were harvested just after the finish of the 24 h stimulation treatment or 24 h later, and three mitochondrial fractions were isolated by differential centrifugation: the M1 fraction (1000 g), the M3 fraction (3000 g) and the M15 fraction (15,000 g). The results obtained in vitro indicate that removal of adrenergic stimulation determines a selective loss of UCP from the lightest mitochondrial fractions (M3 and M15). Similar results were obtained in a situation in vivo (24 h starvation in mice) which is known to lead to a decreased noradrenaline input to brown adipose tissue, with decreased UCP levels. Thus brown adipocytes possess different mitochondrial subpopulations, which exhibit characteristic changes in their UCP turnover in response to thermogenic signals.
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PMID:Selective loss of the uncoupling protein from light versus heavy mitochondria of brown adipocytes after a decrease in noradrenergic stimulation in vivo and in vitro. 757 72

The effects of starvation on the thermogenic parameters of three different mitochondrial subpopulations in brown adipose tissue (BAT) of both post-cafeteria obese and lean rats were investigated. Tissue from different BAT depots from fed and 24 h starved rats were collected, pooled and three mitochondrial subpopulations were isolated by differential centrifugation; the M1 fraction (1000 g), the M3 fraction (3000 g) and the M15 fraction (15,000 g). Thermogenic parameters were measured in the three mitochondrial subtypes, and uncoupling protein (UCP) mRNA was determined in BAT. The results showed that starvation induced a decrease in mitochondrial turnover in BAT from both lean and obese rats. Moreover, a selective net loss of UCP from the lightest mitochondrial fraction (M15) in lean rats, with a concomitant reduction of UCP mRNA was observed. The reductions did not occur in obese rats and, as a result, a change in UCP distribution between the mitochondrial subpopulations was produced, with an increase in the M1 mitochondrial subtype. The lack of response of UCP to starvation observed in BAT of obese rats compared with the decrease seen in lean animals, is a consequence of a different mitochondrial subpopulation composition and/or a different response of a particular subpopulation to starvation.
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PMID:Changes induced by fasting and dietetic obesity in thermogenic parameters of rat brown adipose tissue mitochondrial subpopulations. 891 91

The aim of the present work is to investigate the effect of starvation on brown adipose tissue thermogenic activity with aging. Interscapular brown adipose tissue from female Wistar rats of different ages was used; half of them were fed and the other half were starved for 24 hours. Mitochondria were isolated and mitochondrial protein content, GDP-binding, Cytochrome-c Oxidase activity and uncoupling protein levels were measured. Results show a decrease of all studied parameters, indicating a diminished thermogenic activity with age. The response to starvation is almost the same in all the parameters studied: a general reduction with starvation and a progressive disappearance of this response to starvation with aging. On the whole, these results would indicate a deficient regulation of brown adipose tissue thermogenic activity in old animals, as it happens in other animal models with an alterated thermogenesis.
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PMID:Diminished response to food deprivation of the rat brown adipose tissue mitochondrial uncoupling system with age. 930 33

Mitochondrial uncoupling proteins (UCPs) are transporters that are important for thermogenesis. The net result of their activity is the exothermic movement of protons through the inner mitochondrial membrane, uncoupled from ATP synthesis. We have cloned a third member of the UCP family, UCP3. UCP3 is expressed at high levels in muscle and rodent brown adipose tissue. Overexpression in yeast reduced the mitochondrial membrane potential, showing that UCP3 is a functional uncoupling protein. UCP3 RNA levels are regulated by hormonal and dietary manipulations. In contrast, levels of UCP2, a widely expressed UCP family member, showed little hormonal regulation. In particular, muscle UCP3 levels were decreased 3-fold in hypothyroid rats and increased 6-fold in hyperthyroid rats. Thus UCP3 is a strong candidate to explain the effects of thyroid hormone on thermogenesis. White adipose UCP3 levels were greatly increased by treatment with the beta3-adrenergic agonist, CL214613, suggesting another pathway for increasing thermogenesis. UCP3 mRNA levels were also regulated by dexamethasone, leptin, and starvation, albeit differently in muscle and brown adipose tissue. Starvation caused increased muscle and decreased BAT UCP3, suggesting that muscle assumes a larger role in thermoregulation during starvation. The UCP3 gene is located close to that encoding UCP2, in a chromosomal region implicated in previous linkage studies as contributing to obesity.
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PMID:Uncoupling protein-3 is a mediator of thermogenesis regulated by thyroid hormone, beta3-adrenergic agonists, and leptin. 930 58

Chronic cold exposure stimulates sympathetically driven thermogenesis in brown adipose tissue (BAT), resulting in fat mobilization, weight loss, and compensatory hyperphagia. Hypothalamic neuropeptide Y (NPY) neurons are implicated in stimulating food intake in starvation, but may also suppress sympathetic outflow to BAT. This study investigated whether the NPY neurons drive hyperphagia in rats that have lost weight through cold exposure. Rats exposed to 4 degrees C for 21 days weighed 14% less than controls maintained at 22 degrees C (P < 0.001). Food intake increased after 3 days and remained 10% higher thereafter (P < 0.001). Increase BAT activity was confirmed by 64, 96, and 335% increases in uncoupling protein-1 mRNA at 2, 8, and 21 days. Plasma leptin decreased during prolonged cold exposure. Cold-exposed rats showed no significant changes in NPY concentrations in any hypothalamic regions or in hypothalamic NPY mRNA at any time. We conclude that the NPY neurons are not activated during cold exposure. This is in contrast with starvation-induced hyperphagia, but is biologically appropriate since enhanced NPY release would inhibit thermogenesis causing potentially lethal hypothermia. Other neuronal pathways must therefore mediate hyperphagia in chronic cold exposure.
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PMID:Hyperphagia in cold-exposed rats is accompanied by decreased plasma leptin but unchanged hypothalamic NPY. 945 99

The aim of the present work was to study the effects of various durations of fasting (12, 24 and 72 hours) on brown adipose tissue (BAT) thermogenic parameters--cytrochrome-c-oxidase (COX) activity, GDP-binding activity and uncoupling protein (UCP1) content--and also on morphological features of different mitochondrial subpopulations, obtained by differential centrifugation--M1 (1000 g), M3 (3000 g) and M15 (15,000 g) fractions. The mitochondrial subpopulations showed morphological differences and a different distribution of UCP1 levels and of GDP-binding in all experimental groups. Starvation induced a decrease in the average size for all mitochondrial subtypes. The main changes induced by fasting in thermogenic parameters were observed in the M15 subtype. After the first 24h of starvation, there was a significant decrease of UCP1 levels only in the lightest mitochondrial subpopulation. However, the 72h fasted situation reflected a tendency to increase UCP1 content and UCP1/COX ratio together with a significant decrease of GDP-binding/UCP1 ratio, thus indicating more masked GDP-binding sites. Important fasting-induced changes in both morphological and biochemical parameters in BAT mitochondrial subtypes reflect their role in the physiological response of BAT to starvation.
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PMID:Effect of 12, 24 and 72 hours fasting in thermogenic parameters of rat brown adipose tissue mitochondrial subpopulations. 960 Mar 30

UCP2 and UCP3 are two recently cloned genes with high sequence homology to the gene for uncoupling protein (UCP)-1, which regulates thermogenesis in brown adipose tissue. In the context of the current debate about whether UCP2 and UCP3 in the skeletal muscle may also function as mediators of thermogenesis or as regulators of lipids as fuel substrate, we have examined their mRNA expressions in rat gastrocnemius muscle in response to dietary manipulations known to differentially affect thermogenesis during the phase of weight recovery after starvation. Compared with ad libitum-fed control rats, the refeeding of isocaloric amounts of a low-fat (high-carbohydrate) diet resulted in lower energy expenditure and lower mRNA levels of muscle UCP2 and UCP3. This downregulation of UCP homologs was abolished by the refeeding of a high-fat diet, even though energy expenditure was significantly lower during refeeding on the high-fat than on the low-fat diet. Furthermore, major alterations in the fatty acid composition of the refeeding diet in favor of n-6 polyunsaturated or medium-chain fatty acids resulted in significant increases in energy expenditure, but with no significant changes in the expression of skeletal muscle UCP homologs. Regression analysis of gastrocnemius UCP mRNA levels against parameters that included body composition, energy expenditure, and plasma levels of free fatty acids (FFAs), insulin, and glucose as well as the increase in plasma glucose after a glucose load, revealed that only the latter (an index of insulin resistance) could explain the variability in muscle UCP2 and UCP3 mRNA expressions (r = 0.41, P < 0.02; r = 0.45, P < 0.01, respectively). Taken together, these data are at variance with a role for skeletal muscle UCP2 and UCP3 in dietary regulation (or modulation) of thermogenesis. However, they are consistent with the notion that these UCP homologs may function as regulators of lipids as fuel substrate and raise the possibility that high-fat induced upregulation of muscle UCP2 and UCP3 may be more closely linked to insulin resistance than to changes in circulating FFAs.
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PMID:Post-starvation gene expression of skeletal muscle uncoupling protein 2 and uncoupling protein 3 in response to dietary fat levels and fatty acid composition: a link with insulin resistance. 1033 28

The uncoupling protein UCP1 aids the production of heat by uncoupling respiration from oxidative phosphorylation in brown fat of rodents. UCP1 is down-regulated during starvation to conserve energy. Levels of other uncoupling proteins named UCP2 and UCP3, which are present in skeletal muscle, increase during starvation without changing heat production. Transgenic mice ectopically over-expressing UCP3 lost weight and had less adipose tissue than controls, although they were hyperphagic. It was proposed that muscle UCP3 regulated fat oxidation rather than thermogenesis.
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PMID:The uncoupling proteins UCP2 and UCP3 in skeletal muscle. 1131 Jul 77

During the past few years, there have been two major developments, if not revolutions, in the field of energy balance and weight regulation. The first at the molecular level, which was catalysed by developments in DNA screening technology together with the mapping of the human genome, has been the tremendous advances made in the identification of molecules that play a role in the control of food intake and metabolic rate. The second, at the systemic level, which centered upon the use of modern technologies or more robust analytical techniques for assessing human energy expenditure in response to starvation and overfeeding, has been the publication of several papers providing strong evidence that adaptive thermogenesis plays a much more important role in the regulation of body weight and body composition than previously thought. Within these same few years, several new members of the mitochondrial carrier protein family have been identified in a variety of tissues and organs. All apparently possess uncoupling properties in genetically-modified systems, with two of them (uncoupling protein (UCP) 2 and UCP3) being expressed in adipose tissues and skeletal muscles, which are generally recognised as important sites for variations in thermogenesis and/or in substrate oxidation. Considered as breakthrough discoveries, the cloning of these genes has generated considerable optimism for rapid advances in our molecular understanding of adaptive thermogenesis, and for the identification of new targets for pharmacological management of obesity and cachexia. The present paper traces first, from a historical perspective, the landmark events in the field of thermogenesis that led to the identification of these genes encoding candidate UCP, and then addresses the controversies and on-going debate about their physiological importance in adaptive thermogenesis, in lipid oxidation or in oxidative stress. The general conclusion is that UCP2 and UCP3 may have distinct primary functions, with UCP3 implicated in regulating the flux of lipid substrates across the mitochondria and UCP2 in the control of mitochondrial generation of reactive oxygen species. The distinct functions of these two UCP1 homologues have been incorporated in a conceptual model to illustrate how UCP2 and UCP3 may act in concert in the overall regulation of lipid oxidation concomitant to the prevention of lipid-induced oxidative damage.
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PMID:Uncoupling proteins: their roles in adaptive thermogenesis and substrate metabolism reconsidered. 1150 24


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