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 124,988 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The epidemiology of maintenance dialysis patients and heart failure patients has striking similarities. Both groups have a high prevalence of comorbid conditions, a high hospitalization rate, a low self-reported quality of life, and an excessively high mortality risk, mostly because of cardiovascular causes. Observational studies in both dialysis and heart failure patients have indicated the lack of a significant association between the traditional cardiovascular risk factors and mortality, or the existence of a paradoxic or reverse association, in that obesity, hypercholesterolemia, and hypertension appear to confer survival advantages. The time discrepancy between the 2 sets of risk factors, that is, overnutrition (long-term killer) versus undernutrition (short-term killer) may explain the overwhelming role of malnutrition, inflammation, and cachexia in causing the reverse epidemiology, which may exist in more than 20 million Americans. We have reviewed the opposing views about the concept of reverse epidemiology in dialysis and heart failure patients, the recent Die Deutsche Diabetes Dialyze study findings, and the possible role of racial disparities. Contradictory findings on hyperhomocysteinemia in dialysis patients are reviewed in greater details as a possible example of publication bias. Additional findings related to intravenous iron and serum ferritin, calcium, and leptin levels in dialysis patients may enhance our understanding of the new paradigm. The association between obesity and increased death risk in kidney transplanted patients is reviewed as an example of the reversal of reverse epidemiology. Studying the epidemiology of dialysis patients as the archetypical population with such paradoxic associations may lead to the development of population-specific guidelines and treatment strategies beyond the current Framingham cardiovascular risk factor paradigm.
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PMID:Epidemiology of dialysis patients and heart failure patients. 1653 Jun 5

Ghrelin, identified as an endogenous ligand for the growth hormone secretagogue receptor, functions as a somatotrophic and orexigenic signal from the stomach. Ghrelin has a unique post-translational modification: the hydroxyl group of the third amino acid, usually a serine but in some species a threonine, is esterified by octanoic acid and is essential for ghrelin's biological activities. The secretion of ghrelin increases under conditions of negative energy-balance, such as starvation, cachexia, and anorexia nervosa, whereas its expression decreases under conditions of positive energy-balance such as feeding, hyperglycemia, and obesity. In addition to having a powerful effect on the secretion of growth hormone, ghrelin stimulates food intake and transduces signals to hypothalamic regulatory nuclei that control energy homeostasis. Thus, it is interesting to note that the stomach may play an important role in not only digestion but also pituitary growth hormone release and central feeding regulation. We summarized recent findings on the integration of ghrelin into neuroendocrine networks that regulate food intake, energy balance, gastrointestinal function and growth.
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PMID:Biological, physiological, and pharmacological aspects of ghrelin. 1661 45

Since the earliest reports of human immunodeficiency virus (HIV) disease, undernutrition has been associated with HIV infection, typically with the late stages of the disease (namely acquired immunodeficiency syndrome), and may advance to severe wasting and cachexia. Specific micronutrient deficiencies are also recognized to occur with HIV infection, but their actual effect on the clinical course of the disease is hard to assess. The studies reviewed provide more insight into the complex interface between undernutrition and, in some cases, obesity and HIV/acquired immunodeficiency syndrome and highlight the possibility of alleviating or curing undernutrition by means of simple and comparatively inexpensive dietary adjustments.
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PMID:Nutritional and metabolic abnormalities in pre-AIDS HIV infection. 1670 57

Studies of experimental starvation that were carried out in healthy volunteers during the first half of this century often provide an invaluable source of 'untapped' data. The motivation and desire to gain a better insight into the regulation of body composition by re-analysing these data in the light of more 'modern' concepts of energy partitioning and thermogenesis become irresistible when similar studies can no longer be performed in humans, if only for ethical reasons. This paper brings together new findings, largely centered upon recent re-analysis of data from the classical studies of experimental starvation, semi-starvation and refeeding, and proposes a theory of regulation of body composition during weight recovery in which the cardinal features rest upon three auto-regulatory control systems. These control systems--operating via energy partitioning and two distinct forms of adaptive thermogenesis--have been integrated into a compartmental model for the autoregulation of body composition during cycles of underfeeding/refeeding. This model can be used to explain the individual pattern of lean and fat tissue deposition during weight recovery in situations ranging from rehabilitation after malnutrition/cachexia to the relapse of obesity. It also provides a framework of 'system physiology' for integrating the advances in molecular biology into this area of nutritional energetics.
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PMID:Regulation of body composition during weight recovery: integrating the control of energy partitioning and thermogenesis. 1684 18

The immune and neuroendocrine systems are closely involved in the regulation of metabolism at peripheral and central hypothalamic levels. In both physiological (meals) and pathological (infections, traumas and tumors) conditions immune cells are activated responding with the release of cytokines and other immune mediators (afferent signals). In the hypothalamus (central integration), cytokines influence metabolism by acting on nucleus involved in feeding and homeostasis regulation leading to the acute phase response (efferent signals) aimed to maintain the body integrity. Peripheral administration of cytokines, inoculation of tumor and induction of infection alter, by means of cytokine action, the normal pattern of food intake affecting meal size and meal number suggesting that cytokines acted differentially on specific hypothalamic neurons. The effect of cytokines-related cancer anorexia is also exerted peripherally. Increase plasma concentrations of insulin and free tryptophan and decrease gastric emptying and d-xylose absorption. In addition, in obesity an increase in interleukin (IL)-1 and IL-6 occurs in mesenteric fat tissue, which together with an increase in corticosterone, is associated with hyperglycemia, dyslipidemias and insulin resistance of obesity-related metabolic syndrome. These changes in circulating nutrients and hormones are sensed by hypothalamic neurons that influence food intake and metabolism. In anorectic tumor-bearing rats, we detected upregulation of IL-1beta and IL-1 receptor mRNA levels in the hypothalamus, a negative correlation between IL-1 concentration in cerebro-spinal fluid and food intake and high levels of hypothalamic serotonin, and these differences disappeared after tumor removal. Moreover, there is an interaction between serotonin and IL-1 in the development of cancer anorexia as well as an increase in hypothalamic dopamine and serotonin production. Immunohistochemical studies have shown a decrease in neuropeptide Y (NPY) and dopamine (DA) and an increase in serotonin concentration in tumor-bearing rats, in first- and second-order hypothalamic nuclei, while tumor resection reverted these changes and normalized food intake, suggesting negative regulation of NPY and DA systems by cytokines during anorexia, probably mediated by serotonin that appears to play a pivotal role in the regulation of food intake in cancer. Among the different forms of therapy, nutritional manipulation of diet in tumor-bearing state has been investigated. Supplementation of tumor bearing rats with omega-3 fatty acid vs. control diet delayed the appearance of tumor, reduced tumor-growth rate and volume, negated onset of anorexia, increased body weight, decreased cytokines production and increased expression of NPY and decreased alpha-melanocyte-stimulating hormone (alpha-MSH) in hypothalamic nuclei. These data suggest that omega-3 fatty acid suppressed pro-inflammatory cytokines production and improved food intake by normalizing hypothalamic food intake-related peptides and point to the possibility of a therapeutic use of these fatty acids. The sum of these data support the concept that immune cell-derived cytokines are closely related with the regulation of metabolism and have both central and peripheral actions, inducing anorexia via hypothalamic anorectic factors, including serotonin and dopamine, and inhibiting NPY leading to a reduction in food intake and body weight, emphasizing the interconnection of the immune and neuroendocrine systems in regulating metabolism during infectious process, cachexia and obesity.
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PMID:Hypothalamic integration of immune function and metabolism. 1687 87

Although the adverse health consequences of obesity in the general population have been well documented, recent evidence suggests that obesity is associated with better outcomes in patients with heart failure (HF). Studies of patients with HF that specifically examined the impact of body mass index (BMI) on outcomes have suggested the existence of an "obesity paradox." However, closer examination of these studies raises important questions on the validity of the paradox. First, the diagnosis of HF in obese patients, particularly when made using clinical variables, may not be accurate; the obese patients in these studies may actually be "healthier" than their nonobese comparators. Second, the deleterious effects of cachexia, rather than the salutary ones of obesity, are likely the main reason for the inverse correlation between BMI and HF outcome, especially once the underlying biologic mechanisms behind cachexia and obesity in patients with HF are considered. Furthermore, few studies have specifically examined the more severely obese population (BMI >35 kg/m(2)) when assessing outcomes, and those that have suggest that severely obese patients may have worse outcomes than patients with normal weights or those who are mildly obese. Therefore, a "U-shaped" outcome curve according to BMI for patients with HF may actually exist, in which mortality is greatest in cachectic patients; lower in normal, overweight, and mildly obese patients; but higher again in more severely obese patients. Further prospective studies assessing the impact of more marked degrees of obesity on outcomes in patients with HF are needed to more conclusively determine whether the obesity paradox truly exists.
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PMID:The obesity paradox: fact or fiction? 1699 80

The 350,000 maintenance hemodialysis (MHD) patients in the United States have an unacceptably high mortality rate of >20%/year. Almost half of all deaths are assumed to be cardiovascular. Markers of kidney disease wasting (KDW) such as hypoalbuminemia, anorexia, body weight and fat loss, rather than traditional cardiovascular risk factors, appear to be the strongest predictors of early death in these patients. The KDW is closely related to oxidative stress (SOX). Such SOX markers as serum myeloperoxidase are associated with pro-inflammatory cytokines and poor survival in MHD patients. Identifying the conditions that modulate the KDW/SOX-axis may be the key to improving outcomes in MHD patients. Dysfunctional lipoproteins such as a higher ratio of the high-density lipoprotein inflammatory index (HII) may engender or aggravate the KDW, whereas functionally intact or larger lipoprotein pools, as in hypercholesterolemia and obesity, may mitigate the KDW in MHD patients. Hence, a reverse epidemiology or "bad-gone-good" phenomenon may be observed. Diet and gene and their complex interaction may lead to higher proportions of pro-inflammatory or oxidative lipoproteins such as HII, resulting in the aggravation of the SOX and inflammatory processes, endothelial dysfunction, and subsequent atherosclerotic cardiovascular disease and death in MHD patients. Understanding the factors that modulate the KDW/SOX complex and their associations with genetic polymorphism, nutrition, and outcomes in MHD patients may lead to developing more effective strategies to improve outcomes in this and the 20 to 30 million Americans with chronic disease states such as individuals with chronic heart failure, advanced age, malignancies, AIDS, or cachexia.
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PMID:The kidney disease wasting: inflammation, oxidative stress, and diet-gene interaction. 1701 6

The analyses of large epidemiological databases have suggested that infants and children who show catch-up growth, or adiposity rebound at a younger age, are predisposed to the development of obesity, type 2 diabetes and cardiovascular diseases later in life. The pathophysiological mechanisms by which these growth trajectories confer increased risks for these diseases are obscure, but there is compelling evidence that the dynamic process of catch-up growth per se, which often overlaps with adiposity rebound at a younger age, is characterized by hyperinsulinemia and by a disproportionately higher rate in the recovery of body fat than lean tissue (i.e. preferential 'catch-up fat'). This paper first focuses upon the almost ubiquitous nature of this preferential 'catch-up fat' phenotype across the life cycle as a risk factor for obesity and insulin-related complications - not only in infants and children who experienced catch-up growth after earlier fetal or neonatal growth retardation, or after preterm birth, but also in adults who show weight recovery after substantial weight loss owing to famine, disease-cachexia or periodic dieting. It subsequently reviews the evidence indicating that such preferential catch-up fat is primarily driven by energy conservation (thrifty) mechanisms operating via suppressed thermogenesis, with glucose thus spared from oxidation in skeletal muscle being directed towards de novo lipogenesis and storage in white adipose tissue. A molecular-physiological framework is presented which integrates emerging insights into the mechanisms by which this thrifty 'catch-up fat' phenotype crosslinks with early development of insulin and leptin resistance. In the complex interactions between genetic constitution of the individual, programming earlier in life, and a subsequent lifestyle of energy dense foods and low physical activity, this thrifty 'catch-up fat' phenotype--which probably evolved to increase survival capacity in a hunter-gatherer lifestyle of periodic food shortages--is a central event in growth trajectories to obesity and to diseases that cluster into the insulin resistance (metabolic) syndrome.
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PMID:The thrifty 'catch-up fat' phenotype: its impact on insulin sensitivity during growth trajectories to obesity and metabolic syndrome. 1713 32

We have demonstrated a potent and specific lipolytic effect of natriuretic peptides (NP) in human and primates' fat cells. The lipolytic effect of NP is mediated through intracellular production of cGMP and activation of the cGMP-dependent kinase 1alpha. Local infusion of atrial-NP (ANP), directly within the subcutaneous adipose tissue through a microdialysis catheter, increases lipolysis and stimulates blood flow through its vasodilating effect in lean healthy men. This effect is blunted in overweight men and can be recovered by endurance training. Intravenous infusion of physiological doses of ANP induces lipid mobilization. Higher concentrations of ANP that are encountered during heart failure also stimulate lipid oxidation. ANP activates lipolysis and free fatty acids release from adipose tissue during endurance exercise. This effect is paradoxically amplified when exercise is performed under beta-blockade treatment, because of an enhanced cardiac release of ANP. No gender differences in ANP-induced lipid mobilization during exercise have been found. Heart failure is associated with high circulating levels of NP that could participate to the progression toward cachexia. On contrary, a negative correlation between NP levels and body mass index is found in obese persons. The molecular basis of this inverse correlation is not yet demonstrated from a functional standpoint. Further studies are needed to clearly define the pathophysiological role of NP in obesity and heart failure.
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PMID:[Physiological and pathophysiological features of the control of lipolysis and lipid mobilization by natriuretic peptides]. 1714 64

The central melanocortin system is comprised of discrete populations of neurons and circuits that play a key role in maintaining energy balance. This system can sense levels of peripheral energy stores and can integrate a variety of nutrient, neuronal and hormonal signals to regulate food intake, energy expenditure and nutrient metabolism. Disruption of this system at multiple levels causes obesity in humans and animals. This article reviews the normal physiology and regulation of the central melanocortin system, the abnormalities of this system that cause impaired energy balance in humans and in rodents and the potential to target this system for the treatment of obesity and cachexia.
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PMID:The central melanocortin system and the regulation of energy balance. 1748 53


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