Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0948265 (metabolic syndrome)
 24,271 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Immune activation occurs in response to noxious stimuli such tissue injury, infection, inflammation and malignant neoplasia with the production of cytokines both in the circulation and the central nervous system (CNS). In addition to their fundamental immune functions, cytokines such as the interleukins (ILs), interferons (IFNs) and tumour necrosis factor-alpha also elicit significant pathophysiological effects on feeding behaviour and play prominent roles in the anorexia and cachexia syndrome often seen in chronic disease states. There is now compelling evidence that demonstrates that an important site of cytokine bioactivity is located within the hypothalamus where they appear to modulate appetite and energy homeostasis. Hypercytokinaemia has also been observed in the obese state where it has been proposed that they may play pivotal roles in mediating the detrimental components of the metabolic syndrome including insulin resistance, impaired glucose tolerance, hypertension. dyslipidaemia and increased cardiovascular risk. This review summarises these putative roles of various cytokines in the regulation of feeding in the setting of anorexia-cachexia and obesity.
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PMID:Role of cytokines in regulating feeding behaviour. 1505 11

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

Bilateral non inflammatory salivary gland enlargement (sialadenosis) is seen with a diverse number of diseases. It is commonly recognized in alcoholism, anorexia and bulimia nervosa and HIV infections. The association between diabetes mellitus and sialadenosis has been reported rarely in the last three decades. We report a patient with sialadenosis in association with metabolic syndrome. We discuss the clinical implications of this novel association including possible regression of salivary gland enlargement with intensive glycemic and lipid control.
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PMID:Marked bilateral parotid enlargement in metabolic syndrome: a case report and review of the literature. 1728 56

The incidence of the metabolic syndrome, type 2 diabetes and cardio- and cerebrovascular disease is increasing in the Western world. The adipocyte derived protein adiponectin is thought to have a protective role against these conditions. But why is it so? Is it reasonable to believe that we have adiponectin to gain protection from welfare related diseases? Humans have had a far deadlier foe throughout history than obesity and sedentariness and that is starvation. During starvation, the body is catabolic in order to provide fuel. Catabolism is also seen in patients with advanced cardiac or renal failure, type 1 diabetes and anorexia. These subjects have higher adiponectin levels than controls. In this article, I will put forward the hypothesis that the adiponectin system evolved in order to help us to survive periods of malnourishment.
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PMID:Adiponectin: saving the starved and the overfed. 1750 73

Cannabis sativa L. preparations have been used in medicine for millenia. However, concern over the dangers of abuse led to the banning of the medicinal use of marijuana in most countries in the 1930s. Only recently, marijuana and individual natural and synthetic cannabinoid receptor agonists and antagonists, as well as chemically related compounds, whose mechanism of action is still obscure, have come back to being considered of therapeutic value. However, their use is highly restricted. Despite the mild addiction to cannabis and the possible enhancement of addiction to other substances of abuse, when combined with cannabis, the therapeutic value of cannabinoids is too high to be put aside. Numerous diseases, such as anorexia, emesis, pain, inflammation, multiple sclerosis, neurodegenerative disorders (Parkinson's disease, Huntington's disease, Tourette's syndrome, Alzheimer's disease), epilepsy, glaucoma, osteoporosis, schizophrenia, cardiovascular disorders, cancer, obesity, and metabolic syndrome-related disorders, to name just a few, are being treated or have the potential to be treated by cannabinoid agonists/antagonists/cannabinoid-related compounds. In view of the very low toxicity and the generally benign side effects of this group of compounds, neglecting or denying their clinical potential is unacceptable--instead, we need to work on the development of more selective cannabinoid receptor agonists/antagonists and related compounds, as well as on novel drugs of this family with better selectivity, distribution patterns, and pharmacokinetics, and--in cases where it is impossible to separate the desired clinical action and the psychoactivity--just to monitor these side effects carefully.
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PMID:Cannabinoids in health and disease. 1828 1

On December 13th and 14th a group of scientists and clinicians met in Washington, DC, for the cachexia consensus conference. At the present time, there is no widely agreed upon operational definition of cachexia. The lack of a definition accepted by clinician and researchers has limited identification and treatment of cachectic patient as well as the development and approval of potential therapeutic agents. The definition that emerged is: "cachexia, is a complex metabolic syndrome associated with underlying illness and characterized by loss of muscle with or without loss of fat mass. The prominent clinical feature of cachexia is weight loss in adults (corrected for fluid retention) or growth failure in children (excluding endocrine disorders). Anorexia, inflammation, insulin resistance and increased muscle protein breakdown are frequently associated with cachexia. Cachexia is distinct from starvation, age-related loss of muscle mass, primary depression, malabsorption and hyperthyroidism and is associated with increased morbidity. While this definition has not been tested in epidemiological or intervention studies, a consensus operational definition provides an opportunity for increased research.
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PMID:Cachexia: a new definition. 1871 96

White coat hypertension (WCH) is most likely a disorder associated with metabolic syndrome. The study was performed at the Internal Medicine Polyclinic of Dumlupinar University on routine check-up patients. WCH cases who were overweight or obese and desiring weight loss were divided into two subgroups according to whether they preferred to achieve weight loss by medication or diet therapy. The study included 324 cases (204 females) with WCH, 45 of whom were in normal weight range. Therefore, 86.1% (279) of cases with WCH were either overweight or obese, and 41.3% (134) of all WCH cases had dyslipidemia. Twenty-five cases (14.7%) stopped metformin therapy due to excessive anorexia. At the end of a 6-month period, there were highly significant differences between the two groups with respect to the prevalences of resolved WCH, hyperbetalipoproteinemia, hypertriglyceridemia, dyslipidemia, overweight and obesity, and decreased fasting plasma glucose below 110 mg/dL (P < 0.001 for all). Due to gradually increased prevalences of impaired glucose tolerance, type 2 diabetes mellitus, dyslipidemia, excess body weight, and obesity-like disorders from sustained normotension towards WCH and hypertension (HT) cases, and very high prevalences of excess weight and dyslipidemia in the WCH group, WCH may be an associated disorder of metabolic syndrome rather than just being a predisposing factor of atherosclerosis or HT alone. Thus, the management of WCH should not focus solely on the regulation of blood pressure with antihypertensive medications, but rather on the prevention of future excess weight and various associated disorders, and metformin alone is an effective therapeutic option, most likely due to its powerful inhibitory effect on appetite.
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PMID:Treatment of white coat hypertension with metformin. 1907 83

Many individuals with diabetic nephropathy, the leading cause of chronic kidney disease (CKD) in the United States, progress to stage 5 of CKD and undergo maintenance dialysis treatment. Recent data indicate that in up to one third of diabetic dialysis patients with a presumptive diagnosis of diabetic nephropathy, glycemic control improves spontaneously with the progression of CKD, loss of residual renal function, and the initiation of dialysis therapy, leading to normal-to-low hemoglobin A1c (<6%) and glucose levels, requiring cessation of insulin or other anti-diabetic medications. Potential contributors to this so-called "burnt-out diabetes" include decreased renal and hepatic insulin clearance, a decline in renal gluconeogenesis, deficient catecholamine release, diminished food intake (because of anorexia or diabetic gastroparesis), protein-energy wasting (with resultant loss of weight and body fat), and the hypoglycemic effects of dialysis treatment. Although the concept of "burnt-out diabetes" appears in sharp contradistinction to the natural history of diabetes mellitus, studying this condition and its potential causes and consequences, including the role of genetic factors, may lead to a better understanding of the pathophysiology of metabolic syndrome and diabetes mellitus in the CKD population and in many other individuals with chronic disease states associated with wasting syndrome that can confound the natural history of diabetes.
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PMID:Burnt-out diabetes: impact of chronic kidney disease progression on the natural course of diabetes mellitus. 1912 68

A breakthrough using "reverse pharmacology" identified and characterized acyl ghrelin from the stomach as the endogenous cognate ligand for the growth hormone (GH) secretagogue receptor (GHS-R) 1a. The unique post-translational modification of O-n-octanoylation at serine 3 is the first in peptide discovery history and is essential for GH-releasing ability. Des-acyl ghrelin, lacking O-n-octanoylation at serine 3, is also produced in the stomach and remains the major molecular form secreted into the circulation. The third ghrelin gene product, obestatin, a novel 23-amino acid peptide identified from rat stomach, was found by comparative genomic analysis. Three ghrelin gene products actively participate in modulating appetite, adipogenesis, gut motility, glucose metabolism, cell proliferation, immune, sleep, memory, anxiety, cognition, and stress. Knockdown or knockout of acyl ghrelin and/or GHS-R1a, and overexpression of des-acyl ghrelin show benefits in the therapy of obesity and metabolic syndrome. By contrast, agonism of acyl ghrelin and/or GHS-R1a could combat human anorexia-cachexia, including anorexia nervosa, chronic heart failure, chronic obstructive pulmonary disease, liver cirrhosis, chronic kidney disease, burn, and postsurgery recovery, as well as restore gut dysmotility, such as diabetic or neurogenic gastroparesis, and postoperative ileus. The ghrelin acyl-modifying enzyme, ghrelin O-Acyltransferase (GOAT), which attaches octanoate to serine-3 of ghrelin, has been identified and characterized also from the stomach. To date, ghrelin is the only protein to be octanylated, and inhibition of GOAT may have effects only on the stomach and is unlikely to affect the synthesis of other proteins. GOAT may provide a critical molecular target in developing novel therapeutics for obesity and type 2 diabetes.
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PMID:Ghrelin gene products and the regulation of food intake and gut motility. 2003 70

Energy regulation (EnR) is most important for homoeostatic regulation of physiological processes. Neuroendocrine pathways are involved in EnR. We can separate factors that provide energy-rich fuels to stores [parasympathetic nervous system (PSNS), insulin, insulin-like growth factor-1, oestrogens, androgens and osteocalcin] and those that provide energy-rich substrates to consumers [sympathetic nervous system (SNS), hypothalamic-pituitary-adrenal axis, thyroid hormones, glucagon and growth hormone]. In chronic inflammatory diseases (CIDs), balanced energy-rich fuel allocation to stores and consumers, normally aligned with circadian rhythms, is largely disturbed due to the vast fuel consumption of an activated immune system (up to 2000 kJ day(-1)). Proinflammatory cytokines such as tumour necrosis factor or interleukins 1beta and 6, circulating activated immune cells and sensory nerve fibres signal immune activation to the rest of the body. This signal is an appeal for energy-rich fuels as regulators are switched on to supply energy-rich fuels ('energy appeal reaction'). During evolution, adequate EnR evolved to cope with nonlife-threatening diseases, not with CIDs (huge negative selection pressure and reduced reproduction). Thus, EnR is inadequate in CIDs leading to many abnormalities, including sickness behaviour, anorexia, hypovitaminosis D, cachexia, cachectic obesity, insulin resistance, hyperinsulinaemia, dyslipidaemia, fat deposits near inflamed tissue, hypoandrogenaemia, mild hypercortisolaemia, activation of the SNS (hypertension), CID-related anaemia and osteopenia. Many of these conditions can contribute to the metabolic syndrome. These signs and symptoms become comprehensible in the context of an exaggerated call for energy-rich fuels by the immune system. We propose that the presented pathophysiological framework may lead to new therapeutical approaches and to a better understanding of CID sequence.
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PMID:Energy regulation and neuroendocrine-immune control in chronic inflammatory diseases. 2021 Aug 43


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