Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P05231 (interleukin-6)
 23,907 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Cilostazol, a novel oral phosphodiesterase inhibitor, has shown consistent improvement in exercise tolerance in patients with intermittent claudication (IC). In addition to this effect, cilostazol has previously been shown to have beneficial effects on the dyslipidemia, i.e., combination of high triglycerides with low high-density-lipoprotein cholesterol (HDL-C) levels. Interleukin-6 (IL-6) suppresses the activity of lipoprotein lipase, which modulates the metabolism of triglycerides and HDL-C. To determine whether a reduction of IL-6 contributes to the improvement of lipid profiles, we prospectively investigated the effect of cilostazol (n=16, 100 mg, twice daily) on the changes of lipid profiles and on the association with the changes of IL-6 compared with those of pentoxifylline (n=16, 400 mg, bid) in patients with IC. After eight weeks of administration of cilostazol to patients with IC, walking distances were increased, associated with a 29% decrease in plasma triglycerides and a 13% increase in HDL-C. No significant changes of lipid profiles in the pentoxifylline and placebo groups were observed although a similar improvement in walking distances was achieved in the pentoxifylline group. IL-6 levels were significantly reduced in patients receiving cilostazol as compared with those receiving placebo or pentoxifylline. The cilostazol-induced changes in the IL-6 were positively related to those of triglycerides in the cilostazol group (r=0.63, P<0.05) and negatively related to those of HDL-C (r=-0.55, P<0.05). These findings suggest that in addition to consistent improvement of exercise tolerance, cilostazol may improve lipid profiles by reducing IL-6 release. However, pentoxifylline did not affect lipid profiles although a similar improvement of maximal walking distance (MWD) was achieved.
 ...
PMID:Differential lipogenic effects of cilostazol and pentoxifylline in patients with intermittent claudication: potential role for interleukin-6. 1158 28

Coronary heart disease (CHD) is one of the main leading causes of death worldwide. CHD is a complex condition resulting from numerous gene-gene and gene-environment interactions. A large number of candidate genes exist. We review the evidence for the role of apolipoprotein E, lipoprotein lipase and interleukin-6 in CHD and their interaction with smoking (an environmental risk). The main objective of genetic research into CHD is to provide a complete risk assessment, complementing the well-studied traditional clinical and biochemical risk factors. Unravelling the role that functional gene polymorphisms play in determining risk, and in determining the levels of intermediate phenotypes is crucial to our understanding of the key metabolic pathways and physiology not only in the diseased, but also in the disease-free state. The identification of new molecules (implicated in the relevant metabolic pathways) may subsequently lead to potential targets for therapeutic intervention. Improving our molecular understanding may also lead to the development of improved diagnostics. Sequencing of the entire genome is now a reality. Advances in technology, such as the development of "gene chips" may allow us to study 100 000 genes at a time on a single chip. Such advances will amplify the power available to us in the realms of research into genetic physiology and interaction with environmental stimuli. The insights that these novel approaches may yield are eagerly awaited.
 ...
PMID:The molecular genetics of cardiovascular disease: clinical implications. 1254 51

Cardiovascular disease is common in patients with chronic kidney disease (CKD). As renal function fails, many patients become progressively malnourished, as evidenced by reduced levels of albumin, prealbumin, and transferrin. Malnourished patients have increased levels of C reactive protein (CRP), interleukin-6 (IL-6), and concomitant cardiovascular disease when they reach end stage. Many diseases that cause CKD, diabetes, and hypertension are also associated with cardiovascular disease. Thus the direct effect of renal failure per se directly contributing to the inflammation-malnutrition-atherosclerosis paradigm is not completely established in early stages of CKD. Some aspects of progressive renal failure, however, cause changes in plasma composition and endothelial structure and function that favor vascular injury. As renal function fails, hepatic apo A-I synthesis decreases and HDL levels fall. HDL is an important antioxidant and defends the endothelium from the effects of cytokines. Inflammation causes further structural and functional abnormalities in HDL. Apolipoprotein C III (apo C III), a competitive inhibitor of lipoprotein lipase is increased in CKD. Serum triglyceride levels increase as a result of accumulation of intermediate-density lipoprotein (IDL) comprising VLDL and chylomicron remnants. These impede vascular relaxation and are associated with cardiovascular disease. Activation of the renin angiotensin axis is a component of many renal diseases and adaptation to loss of renal mass. Angiotensin II (AngII) activates NADPH oxidases, leading to production of the superoxide anion and decreased availability of nitric oxide (NO), further impairing vascular function. H(2)O(2), produced as a consequence of superoxide dismutation, stimulates vascular cell proliferation and hypertrophy. Leukocyte-derived myeloperoxidase functions as an "NO Oxidase" in the inflamed vasculature and contributes to decreased NO bioavailability and compromised vascular reactivity. The changes in lipoprotein composition and structure as well as AngII-mediated alterations in endothelial function amplify the effect of subsequent inflammatory events.
 ...
PMID:The role of oxidative stress-altered lipoprotein structure and function and microinflammation on cardiovascular risk in patients with minor renal dysfunction. 1497 55

Obesity is associated with increased incidence of cardiovascular mortality. However, the mechanisms that link increased fat mass with hypercholesterolemia, hypertension, endothelial dysfunction and coronary heart disease have not been fully elucidated. Unravelling the diverse neuroendocrine systems, which regulate energy balance and body fat has been a long-standing challenge in biology, with obesity as an increasingly important public health focus. Until recently, the adipocyte has been considered only a passive tissue for the storage of excess energy in the form of fat. However, there is now compelling evidence that adipocytes act as endocrine, secretory cells. It has been shown that several hormones, growth factors and cytokines are actually expressed in white adipose tissue. In a dynamic view of the adipocyte a wide range of signals emanates from white adipose tissue such as tumour necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6), and their respective soluble receptors. White adipose tissue also secretes important regulators of lipoprotein metabolism like lipoprotein lipase (LPL), apolipoprotein E (apoE) and cholesteryl ester transfer protein (CETP). The increasing number of products secreted by adipocytes also includes leptin, estrogen, angiotensinogen, plasminogen activator inhibitor-1 (PAI-1), tissue factor and transforming growth factor-beta (TGF-beta). Nitric oxide synthase (NOS) has been also reported to be expressed in white adipose tissue. Acylation stimulating protein (ASP), adipophilin, adipoQ, adipsin, monobutyrin, agouti protein and factors related to pro-inflammatory and immune processes have also been shown to be released by white adipocytes. Since blood vessels express receptors for most of the adipocyte-derived factors, adipose tissue seems to play a key role in cardiovascular physiology through the existence of a network of local and systemic signals. The current knowledge in this field will be reviewed in the broader perspective of cardiovascular physiology and pathophysiology.
 ...
PMID:The adipose tissue as a source of vasoactive factors. 1532 Jul 86

Oncostatin M (OSM) is a multifunctional cytokine of the interleukin-6 family and has been implicated in embryonic development, differentiation, inflammation, and regeneration of liver and bone. In the present study, we demonstrated that treatment of human adipose mesenchymal stem cells (hADSCs) with OSM-attenuated adipogenic differentiation, as indicated by decreased accumulation of intracellular lipid droplets and down-regulated expression of adipocytic markers, such as lipoprotein lipase and PPARgamma. However, OSM treatment stimulated osteogenic differentiation, as demonstrated by the increase in matrix mineralization and expression levels of osteogenic differentiation markers, including alkaline phosphatase, Runx2, and osteocalcin. OSM treatment induced activation of JAK2, JAK3, and ERK in hADSCs, and pre-treatment of hADSCs with the JAK2 inhibitor, AG490, significantly restored the OSM-induced inhibition of adipogenic differentiation. Whereas, the JAK3 inhibitor, WHI-P131, and the MEK inhibitor, U0126, had no effects on the anti-adipogenic activity of OSM. On the other hand, the pro-osteogenic activity of OSM was prevented by treatment of the cells with WHI-P131 or U0126, but not with AG490. These results indicate that distinct signaling pathways, including JAK2, JAK3, and MEK-ERK, play specific roles in the OSM-induced anti-adipogenic and pro-osteogenic differentiation of hADSCs.
 ...
PMID:Oncostatin M promotes osteogenesis and suppresses adipogenic differentiation of human adipose tissue-derived mesenchymal stem cells. 1722 68

Dietary model of steatohepatitis was established by feeding mice a methionine choline deficient (MCD) diet. Mice on MCD or control diet for 3 weeks were treated with or without NO-1886, a newly synthetic lipoprotein lipase (LPL) activator. In a separate experiment, NO-1886 was given after pre-treatment with 3 weeks of MCD diet. NO-1886 significantly reduced MCD-induced inflammation by repressing levels of hepatic lipid peroxides and pro-inflammatory tumor necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6), and cyclooxygenase-2 (COX-2). In addition, NO-1886 dampened hepatic steatosis via accelerating fatty acid oxidation caused by enhanced expression of PPARalpha, cytochrome P450-10 (Cyp4a10), and Acyl-CoA oxidase (ACO). It failed to regulate genes of fatty acid uptake and synthesis pathways. In conclusion, NO-1886 ameliorated and induced regression of experimental steatohepatitis via increasing endogenous LPL activation resulting in suppression on pro-inflammatory factors and reduction of hepatic fatty acids. These findings indicate that NO-1886 is a potential therapeutic agent for steatohepatitis.
 ...
PMID:Lipoprotein lipase activator ameliorates the severity of dietary steatohepatitis. 1735 May 93

Obesity is a complex disease, which in many cases appears as a polygenic condition affected by environmental factors (mainly unbalanced dietary patterns and physical inactivity). In this context, the weight loss response to dietary interventions varies widely and predictive factors of successful slimming including those concerned with the individual's genetic make-up are poorly understood. Indeed, a number of genes involved in the regulation of energy expenditure, appetite, lipid metabolism and adipogenesis have been reported to affect the risk of treatment failure in some obese subjects. Some candidate genes for the prognosis of weight loss response related to energy expenditure are those codifying for the adrenergic receptors (ADBRs) and uncoupling proteins (UCPs), while genes related to appetite potentially affected by energy restriction are leptin (LEP), leptin receptor (LEPR), melanocortin pathways genes (MC3R, POMC) and the serotonin receptor. Furthermore, adipogenesis related genes such as peroxisome proliferator-activated receptor (PPAR gamma 2) and genes related to cytokines such as interleukin-6 (IL-6) and lipid metabolism including hepatic lipase (LIPC), perilipin (PLIN) and lipoprotein lipase (LPL) have also been associated to the weight lowering outcome induced by hypocaloric diets. Therefore, this review shows preliminary evidence from human studies that support the existence of a genetic component in the fat reduction process associated to a negative energy balance.
 ...
PMID:Genotype-dependent response to energy-restricted diets in obese subjects: towards personalized nutrition. 1829 17

The hypertriglyceridemia of infection is produced by many of the cytokines that regulate the immune response, including the tumor necrosis factors, interleukin-1, interleukin-6, and the interferons. In rodents, this hypertriglyceridemia is primarily due to the ability of these cytokines to stimulate hepatic lipogenesis and very low density lipoprotein production without causing significant changes in adipose tissue lipoprotein lipase or triglyceride clearance. Induction of hypertriglyceridemia is not directly linked to the syndrome of wasting. Rather, the increase in hepatic production of lipoproteins is part of the acute-phase response and may contribute to host defense.
 ...
PMID:Tumor necrosis factor, cytokines, and the hyperlipidemia of infection. 1841 Nov 85

The mechanisms contributing to BW gain following ovariohysterectomy in domestic cats are poorly understood. Moreover, the effects of food restriction to maintain BW following spaying have been poorly studied. Thus, our primary objective was to determine the effects of spaying and food restriction to maintain BW on adipose and skeletal muscle mRNA abundance and activity levels in cats. After a 4-wk baseline period (wk 0), 8 adult (approximately 1.5 yr old) domestic shorthair cats were spayed and fed to maintain BW for 12 wk. After 12 wk, cats were fed ad libitum for an additional 12 wk. Body composition was determined, activity levels were measured, and adipose and muscle biopsies were collected at wk 0, 12, and 24. Fasting blood samples were collected at wk 0, 6, 12, 18, and 24. To maintain BW post-spay, food intake was decreased (P < 0.05) by 30%. During this phase, mRNA abundance of adipose tissue lipoprotein lipase and leptin was decreased (P < 0.05), representing only 52 and 23% of baseline expression, respectively. Interleukin-6 mRNA, however, was increased (P < 0.05) 2-fold. Physical activity was decreased (P < 0.05) by wk 12, most dramatically during the dark period (approximately 20% of baseline activity). During ad libitum feeding (wk 12 to 24), food intake, BW, body fat percentage, and total fat mass were greatly increased (P < 0.05). Compared with wk 0, circulating leptin concentrations tended to increase (P < 0.10) by wk 18 and 24 (4.45 vs. 10.02 and 9.14 ng/mL, respectively), whereas glucose (91 vs. 162 mg/dL) and triacylglyceride (30 vs. 48 mg/dL) concentrations were increased (P < 0.05) by wk 24. Adipose tissue lipoprotein lipase, hormone sensitive lipase, and adiponectin mRNA were decreased (P < 0.05) at wk 24. Adipose interleukin-6 mRNA was increased (P < 0.05) at 24 wk. Physical activity was further decreased (P < 0.05) by wk 24, during the light (60% of baseline) and dark (33% of baseline) periods. In summary, spaying and food restriction affect physical activity levels and several genes associated with lipid metabolism (decreased lipoprotein lipase), food intake (decreased leptin expression), and insulin insensitivity (increased interleukin-6). By identifying these changes, targets for nutritional intervention or lifestyle management have been identified that may curb the risk of obesity and related disorders in spayed cats.
 ...
PMID:Impact of ovariohysterectomy and food intake on body composition, physical activity, and adipose gene expression in cats. 1899 63

Adipose tissue is one of the main sources of inflammatory mediators, with interleukin-6 (IL-6) among them. Although high systemic levels of inflammatory mediators are cachectogenic and/or anorexic, today it is a widely propagated thesis that in the background of obesity, a low level of chronic inflammation can be found, with IL-6 being one of the many suggested mediators. This paper reviews the studies describing elevated IL-6 levels in obese patients and the role of adipocytes and adipose-tissue macrophages in the production of IL-6. The secretion of IL-6 is regulated by several physiologic or pathologic factors: hormones, cytokines, diet, physical activity, stress, hypoxia, and others. Adipose tissue-derived IL-6 may have an effect on metabolism through several mechanisms, including adipose tissue-specific gene expression, triglyceride release, lipoprotein lipase downregulation, insulin sensitivity, and so on. Having a better understanding of these mechanisms may contribute to the prevention and treatment of obesity.
 ...
PMID:The major inflammatory mediator interleukin-6 and obesity. 1954 91


<< Previous 1 2 3 4 5 Next >>