摘要:

Purpose of reviewOrexins, also called hypocretins, are a pair of neuropeptides expressed by a specific population of neurons in the lateral hypothalamic area, a region of the brain implicated in feeding, arousal and motivated behaviour. The purpose of this review is to summarize recent relevant findings on orexins, and discuss the physiological roles of these peptides.Recent findingsRecent findings suggest that orexin neurons provide a critical link between the peripheral energy balance and central nervous system mechanisms that coordinate sleep‐wakefulness and motivated behaviours such as food seeking, especially in the physiological state of fasting stress.SummaryOrexin (hypocretin) neurons interact with feeding centres in the hypothalamus, arousal and sleep‐wakefulness centres in the brainstem, sympathetic and parasympathetic nuclei and the limbic system. The central administration of orexin dose‐dependently increases food intake, waking time, motor activity, and metabolic rate, as well as heart rate and blood pressure in many species. Recent electrophysiological studies have shown that orexin neurons are regulated by metabolic cues, including leptin, glucose, and ghrelin, as well as monoamines and acetylcholin. Orexin neurons thus have the requisite functional interactions with hypothalamic feeding pathways and monoaminergic‐cholinergic centres in the brain stem, and regulation by nutritional factors, to suggest that they may be an important cellular link in the integration of adaptive behaviour associated with arousal and energy homeostasis.

ISSN:1363-1950    

出版商:OVID    

年代:2003

数据来源: OVID

摘要:

Purpose of reviewObesity is a major public health problem and is associated with significant morbidity and mortality from coronary heart disease and type 2 diabetes. The population is becoming increasingly obese, yet for individuals weight is regulated within a narrow range. This regulation depends on the balance between energy intake (in the form of food) and energy expenditure. Thus in order to regulate weight and energy stores, the body must be able to control food intake accurately. Recently there has been a remarkable increase in our understanding of the molecular mechanisms regulating food intake and energy homeostasis.Recent findingsThere is increased understanding of the central pathways by which known neurotransmitters affect food intake. These include peptides expressed in hypothalamic nuclei, but other brain regions including brain stem, amygdala and nucleus accumbens, are also important. Further central transmitters have been identified, such as that encoded by the gene identified in mice with the mahoganoid mutation, and roles for known transmitters have been elucidated, such as endocannabinoids and acetylcholine. There is new evidence regarding peripheral modulation of these pathways including the role of ghrelin as an initiator of feeding, and peptide YY as a medium‐term satiety signal.SummaryComplex central circuitry controls food intake and energy expenditure. Circulating factors that modulate these pathways have appetite stimulation or satiety effects. These are potentially important targets for therapy in obesity. Single‐gene models of obesity in animals are important in understanding these pathways, however human clinical correlates for genetically determined obesity are uncommon.

ISSN:1363-1950    

出版商:OVID    

年代:2003

数据来源: OVID

摘要:

Purpose of reviewThe models currently proposed for the genetic architecture of obesity are critically reviewed in the light of recent developments in the search for genetic causes of this condition.Recent findingsAs for many other ‘complex’ diseases, most of the genetic variants predisposing to human obesity have not yet been identified. To date, investigation of the genetic contribution to obesity has been conducted according to two main hypotheses. The common disease/common variant hypothesis proposes that the genetic architecture of complex diseases (including obesity) is likely to consist of a limited number of alleles, each conferring a small increase in risk to the individual. Alternatively, it has also been proposed that complex diseases such as obesity may instead result from the effects of a large number of rare variants, with substantial allelic heterogeneity at disease‐causing loci. These two hypotheses have shaped strategies for the identification of disease genes, including the use of linkage analysis, association studies and the systematic sequencing of candidate genes. Linkage studies have recently been very successful in identifying new genes in which mutations cause rare monogenic syndromes of obesity. In common obesity, numerous linkage and association studies have suggested that an increasing number of genetic loci could be involved. Overall, however, these studies have failed to identify the causal genetic variants. In contrast, the direct sequencing of well‐chosen candidate genes has led to the identification of numerous rare alleles causing both syndromic and common obesity, which are less severe forms of the condition in humans.SummaryThe genetic architecture of obesity is still a matter of debate. The previously accepted hypothesis of a small number of common variants has been undermined by the low reproducibility of association studies and inconsistencies among genome scans for obesity. While high‐throughput association mapping of candidate regions holds some promise for the identification of common susceptibility alleles, it must also be considered that the genetic predisposition to obesity may instead result from multiple rare variants in a large number of genes.

ISSN:1363-1950    

出版商:OVID    

年代:2003

数据来源: OVID

摘要:

Purpose of reviewThyroid hormones are key regulators of development and metabolism that modulate transcription via nuclear receptors. Although the molecular actions of thyroid hormones have been thoroughly studied, their pleiotropic effects are mediated by complex changes in expression of numerous, but still largely unknown, target genes. This review summarizes the recent advances in the characterization of target genes in different organs.Recent findingsNew patterns of gene expression regulation have been described in tissues with known physiological actions of thyroid hormone, that is brain, liver, skeletal and cardiac muscles, and brown and white adipose tissues. The studies have benefited from the numerous transgenic models with altered thyroid hormone receptor expression and the application of DNA microarray technology to mouse and human tissues.SummaryData on thyroid hormone‐mediated control of gene expression and on the roles of the different thyroid hormone receptor isoforms bring new clues to our understanding of the molecular mechanisms of thyroid hormone action in physiological situations and, most importantly, in diseases associated with alterations of the thyroid status.

ISSN:1363-1950    

出版商:OVID    

年代:2003

数据来源: OVID

ISSN:1363-1950    

出版商:OVID    

年代:2003

数据来源: OVID

摘要:

Purpose of reviewThis review presents the latest clinical applications of bioelectrical impedance analysis. It discusses the evaluation of nutritional status by using fat‐free mass and body fat, percentiles of fat‐free mass and body fat, height‐normalized fat‐free mass and body fat mass indices and a resistance/reactance vector graph.Recent findingsFat‐free mass and body fat can be used to evaluate nutritional status by comparing individuals or groups of individuals with themselves or with reference values. Percentile distributions are also useful in determining whether individuals or groups fall within the population range. Percentile ranks can also be used to define nutritional depletion and obesity. The use of the fat‐free mass and body fat mass indices has the advantage of compensating for differences in body height. The use of low, normal, high and very high fat‐free mass and body fat mass indices ranges that correspond to underweight, normal, overweight and obese body mass index categories further aid in the nutritional assessment process. With vector bioelectrical impedance analysis, an individual impedance vector is compared with the 50, 75, and 95% tolerance ellipses calculated in the reference, healthy population, allowing evaluation in any clinical condition. More accurate estimates of conventional bioelectrical impedance analysis equations might be obtained in individuals with a normal impedance vector.SummaryThe assessment of fat‐free mass and body fat provides valuable information about changes in body composition with weight gain or loss and physical activity, and during ageing. The use of percentiles and height‐normalized fat‐free mass and body fat permit the classification of patients as under or overnourished.

ISSN:1363-1950    

出版商:OVID    

年代:2003

数据来源: OVID

摘要:

Purpose of reviewLeptin, a member of the interleukin‐6 superfamily of proteins, modifies the gene expression and synthetic pathway of both orexigenic (appetite‐stimulating) and anorexigenic (appetite‐suppressing) molecules in the hypothalamus, thereby controlling adipocyte energy stores. Lack of leptin secretion or the inability of leptin to interact with these molecules via leptin receptors, prevent leptin's effects and lead to obesity. It is not well known, however, how these feeding‐regulatory molecules are affected in cachexia associated with cancer and other critical conditions in which cytokines such as interleukin‐1 and interleukin‐6 may have a key role.Recent findingsDecreased leptin and increased leptin‐like signaling by cytokines in the hypothalamus are the hallmark of obesity and cachexia, respectively. Increased orexigenic and impaired anorexigenic signaling produces hyperphagia and obesity, while the reverse applies to anorexia‐cachexia in which adaptive feeding response to starvation is lacking or insufficient.SummaryImbalanced operation of orexigenic and anorexigenic circuits perturbs the homeostatic loop of body weight regulation leading to either obesity or cachexia. Modifiers of the central effects on appetite and energy metabolism could restore the balance and be effective for treating both conditions. In cachexia this may especially be true when combined with agents that target muscle and protein breakdown.

ISSN:1363-1950    

出版商:OVID    

年代:2003

数据来源: OVID

摘要:

Purpose of reviewThe aim of the present review is to summarize and update the role of different cytokines in the pathogenesis of cancer cachexia and to provide therapeutic strategies based on cytokine action.Recent findingsCancer cachexia is a syndrome characterized by a marked weight loss, anorexia, asthenia and anemia. The cachectic state is invariably associated with the presence and growth of the tumor and leads to a malnutrition status due to the induction of anorexia or decreased food intake. In addition, the competition for nutrients between the tumor and the host leads to an accelerated starvation state which promotes severe metabolic disturbances in the host, including hypermetabolism, which leads to an increased energetic inefficiency. Different cytokines are clearly implicated in this process, possibly being responsible for anorexia, hypermetabolism and many other metabolic abnormalities, such as muscle proteolysis and apoptosis.SummaryAlthough the search for the cachectic factor(s) started a long time ago, and although many scientific and economic efforts have been devoted to its discovery, we are still a long way from knowing the whole truth. A lot of progress has been made, however, in understanding the role of different cytokines ‐ tumor necrosis factor and IL‐6 in particular ‐ in muscle wasting associated with cancer cachexia, perhaps the most paradigmatic feature of this complex syndrome.

ISSN:1363-1950    

出版商:OVID    

年代:2003

数据来源: OVID

摘要:

Purpose of reviewMuscle protein wasting frequently complicates patient outcome in several chronic pathologies. The underlying mechanisms remain largely obscure, although studies on experimental models have clarified that a complex interplay of different factors such as nutrient supply, classical hormones, cytokines and other less well defined factors likely concur in causing muscle depletion. The aim of the present review is to highlight some crucial points in the interpretation of the data available about the contribution of the different proteolytic systems, with particular reference to the ubiquitin‐proteasome system, in the onset of muscle protein wasting in disease states.Recent findingsMuch effort has been directed to understanding the role of different signals, transduction pathways, and proteolytic mechanisms in the acceleration of muscle protein catabolism. Several reports propose that ATP‐ubiquitin‐dependent proteolysis plays a critical role in the enhancement of muscle protein catabolism observed in different pathological states. Other papers, however, suggest that the lysosomal or the calcium‐dependent proteolytic pathways or both may be involved. Finally, the studies have been extended to evaluate the possibility of interfering pharmacologically with the onset of muscle protein hypercatabolism.SummaryAs the present overview points out, several questions still remain unanswered in the issue of muscle wasting. While many different signals that have the potential to enforce the acceleration of muscle protein breakdown have been identified, it is largely unknown how they are transduced and converge into the hypercatabolic response and how the proteolytic pathways involved are activated. The concept seems to emerge that there may be a coordinated action of different proteolytic pathways in setting up muscle protein turnover towards excess catabolism.

ISSN:1363-1950    

出版商:OVID    

年代:2003

数据来源: OVID

摘要:

Purpose of reviewTo discuss the possible relationship between long‐chain polyunsaturated fatty acids, cytokines, anandamides, nitric oxide, leptin, various neurotransmitters in the brain, and their role in anorexia of acute and chronic inflammatory conditions and cancer.Recent findingsRecent studies have shown that long‐chain polyunsaturated fatty acids, especially the omega‐3 series, have antiinflammatory actions, increase the concentrations of anandamides, enhance the levels of acetylcholine and nitric oxide and modulate the concentrations and actions of various neurotransmitters, including leptin, in the brain. Patients suffering from acute and chronic inflammatory conditions have low tissue concentrations of various long‐chain polyunsaturated fatty acids, and high levels of proinflammatory cytokines that can cause anorexia and decrease food intake.SummaryIt is suggested that supplementation of long‐chain polyunsaturated fatty acids may have a role in the prevention and treatment of acute and chronic inflammatory conditions, improving anorexia associated with these conditions.

ISSN:1363-1950    

出版商:OVID    

年代:2003

数据来源: OVID