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)

Despite mounting evidence that depression increases risk for cardiovascular morbidity and mortality, little is known about the mechanisms responsible for this association. The current study examined the inter-relationships between depression, adiposity, and inflammatory molecules implicated in the pathogenesis of coronary heart disease. One hundred adults were enrolled. Half were clinically depressed; the others were matched controls with no history of psychiatric illness. All subjects were in excellent health, defined as having no acute infectious disease, chronic medical illness, or prescribed medication regimen. Structural equation modeling yielded support for a model in which depressive symptoms promote weight accumulation, which in turn activates an inflammatory response through two distinct pathways: expanded adipose tissue release of interleukin-6 and leptin-induced upregulation of interleukin-6 release by white blood cells (CFI =.99; NNFI =.99; RMSEA =.05). It did not support a sickness behavior model in which the inflammatory molecules arising from expanded adipose tissue promote depressive symptoms.
 ...
PMID:Pathways linking depression, adiposity, and inflammatory markers in healthy young adults. 1283 30

Prostate cancer is one of the leading causes of death among men in the United States, and acquisition of hormone resistance (androgen independence) by cancer cells is a fatal event during the natural history of prostate cancer. Obesity is another serious health problem and has been shown to be associated with prostate cancer. However, little is known about the molecular basis of this association. Here we show that factor(s) secreted from adipocytes stimulate prostate cancer cell proliferation. Leptin is one of the major adipose cytokines, and it controls body weight homeostasis through food intake and energy expenditure. We identify leptin as a novel growth factor in androgen-independent prostate cancer cell growth. Strikingly, leptin stimulates cell proliferation specifically in androgen-independent DU145 and PC-3 prostate cancer cells but not in androgen-dependent LNCaP-FGC cells, although both cell types express functional leptin receptor isoforms. c-Jun NH2-terminal kinase (JNK) has been shown recently to play a crucial role in obesity and insulin resistance. Intriguingly, leptin induces JNK activation in androgen-independent prostate cancer cells, and the pharmacological inhibition of JNK blocked the leptin stimulation of androgen-independent prostate cancer cell proliferation. This suggests that JNK activation is required for leptin-mediated, androgen-independent prostate cancer cell proliferation. Furthermore, other cytokines produced by adipocytes and critical for body weight homeostasis cooperate with leptin in androgen-independent prostate cancer cell proliferation: interleukin-6 and insulin-like growth factor I demonstrate additive and synergistic effects on the leptin stimulation of androgen-independent prostate cancer cell proliferation, respectively. Therefore, adipose cytokines, as well as JNK, are key mediators between obesity and hormone-resistant prostate cancer and could be therapeutic targets.
 ...
PMID:Prostate cancer cell-adipocyte interaction: leptin mediates androgen-independent prostate cancer cell proliferation through c-Jun NH2-terminal kinase. 1290 51

It is well known that obesity is associated with insulin resistance and an increased risk for type 2 diabetes mellitus. Formerly it was postulated that increased lipolysis and consequently free fatty acid (FFA) production, from with triglycerides overloaded fat cells, would disrupt glucose homeostasis via Randle's hypothesis. Lipodystrophy, however, also leads to insulin resistance. Recently it has become clear that adipose tissue functions as an endocrine organ and secretes numerous proteins in response to a variety of stimuli. These secreted proteins exert a pleiotropic effect. The proteins that are involved in glucose and fat metabolism and hence can influence insulin resistance are discussed in this paper. They include leptin, resistin, adiponectin, acylation-stimulating protein, tumour necrosis factor-alpha and interleukin-6. The stimuli for production and the site and mechanism of action in relation to insulin resistance will be discussed. None of these proteins are, however, without controversy with regard to their mechanism of action. Furthermore, some of these proteins may influence each other via common signalling pathways. A theory is presented to link the interrelationship between these adipocyte secretory products and their effect on insulin resistance.
 ...
PMID:Adipose tissue as an endocrine organ: impact on insulin resistance. 1294 64

Exercise training is associated with peripheral-cellular and central-cerebral processes, hormonal-neuronal regulation and transmission mechanisms. During the acute training response, peripheral cellular mechanisms are mainly metabolostatic to achieve energy supply and involve associated cytokine and hormonal reactions. Glycogen deficiency is associated with increased expression of local cytokines (interleukin-6, IL-6), decreased expression of glucose transporters, increased cortisol and decreased insulin secretion and beta-adrenergic stimulation. A nutrient-sensing signal of adipose tissue may be represented by leptin which, as for insulin, IL-6 and insulin-like growth-factor I (IGF-I), has profound effects on the hypothalamus and is involved in the metabolic hormonal regulation of exercise and training. Muscle damage and repair processes may involve the expression of inflammatory cytokines (e.g. tumour necrosis factor-alpha, TNF-alpha) and of stress proteins (e.g. heat shock protein 72). During overreaching and overtraining, a myopathy-like state is observed in skeletal muscle with depressed turnover of contractile proteins (e.g. in fast-type glycolytic fibres with a concomitant increase in slow type myosins). These alterations are influenced by exercise-induced hypercortisolism, and by decreased somatotropic hormones (e.g. IGF-I). The hypothalamus integrates various error signals (metabolic, hormonal, sensory afferents and central stimuli) and therefore pituitary releasing hormones represent the functional status of an athlete and long-term hypothalamic hormonal and sympathoadrenal downregulation are some of the prominent hormonal signs of prolonged overtraining and performance incompetence syndrome.
 ...
PMID:New aspects of the hormone and cytokine response to training. 1460 61

It is now recognized that the WAT (white adipose tissue) produces a variety of bioactive peptides, collectively termed "adipokines". Alteration of WAT mass in obesity or lipoatrophy affects the production of most adipose secreted factors. Since both conditions are associated with insulin resistance, the idea has emerged that certain adipokines might influence insulin action. Among these, tumour necrosis factor alpha, interleukin-6 and resistin are increased in the obese state and interfere negatively with insulin-mediated processes. Conversely, leptin and adiponectin exert an insulin-sensitizing effect, at least in part by favouring tissue fatty-acid oxidation through AMP-activated kinase activation. Obesity-induced insulin resistance has been linked to leptin resistance and decreased plasma adiponectin, while administration of leptin and adiponectin normalizes plasma levels in lipoatrophic mice and reverses insulin resistance. Thiazolidinedione anti-diabetic agents increase endogenous adiponectin production in rodents and humans, supporting the idea that drugs targeting adipokines might represent a new therapeutic approach to sensitize peripheral tissues to insulin.
 ...
PMID:Extending the glucose/fatty acid cycle: a glucose/adipose tissue cycle. 1464 Oct 17

The prevalence of overweight and obesity continues to increase rapidly in the United States, with more than half of all adults currently overweight or obese. In general, people become obese because of a combination of inherited genes and a lifestyle consisting of low levels of physical activity and consumption of excess calories. Obesity, especially the central or visceral type, is a predisposing factor for the development of type 2 diabetes mellitus, hypertension, and cardiovascular disease (CVD). Obesity and type 2 diabetes are associated with insulin resistance. The relation among obesity, insulin resistance, and CVD appears to develop at a relatively young age. Central obesity is linked with hyperinsulinemia, insulin resistance, dyslipidemia, and proinflammatory and prothrombotic clinical states. Adipose tissue synthesizes and secretes biologically active molecules that may affect CVD risk factors. These chemical messengers include adiponectin, resistin, leptin, plasminogen activator inhibitor-1, tumor necrosis factor-alpha, and interleukin-6. In overweight and obese individuals, weight loss may improve insulin sensitivity, leading to reduction in risk factors for CVD and, consequently, the potential for cardiovascular events. Agents that improve insulin sensitivity, such as the thiazolidinediones, have been shown to reduce visceral obesity. Decreases in visceral adipose tissue contribute to improvements in insulin sensitivity and blood pressure, and weight loss reduces serum levels of triglycerides and low-density lipoprotein cholesterol while increasing serum levels of high-density lipoprotein cholesterol. Reduction of risk factors suggests that the development of cardiovascular disease will be reduced by the improvement of insulin sensitivity and weight loss.
 ...
PMID:Obesity as a cardiovascular risk factor. 1467 64

Metabolic and nutritional derangements are prominent features of the uremic syndrome. Recent evidence suggest that several large-molecular-weight molecules that often are elevated in uremia, such as leptin, ghrelin, and proinflammatory cytokines, may have nutritional impact in this patient group. On the basis of present knowledge, these compounds could be regarded as suspected but not established uremic toxins. The discovery of the ob gene, its product leptin, and cerebral leptin receptors has undoubtedly widened our understanding of obesity and the underlying molecular and physiologic mechanisms that regulate food intake and body weight. Moreover, the recent discovery of leptin receptor isoforms in several peripheral organs suggests that leptin besides having a central function also has several important peripheral biological functions. Because uremic patients in general have an inappropriate elevation of circulatory leptin, further research is necessary to determine the potential biological effects of elevated leptin levels in end-stage renal disease. Also, because many symptoms and findings prevalent in the uremic syndrome are known to be associated with elevated levels of proinflammatory cytokines, such as interleukin-6, future studies are needed to evaluate the role of specific anti-inflammatory treatment strategies in malnourished uremic patients.
 ...
PMID:Leptin, ghrelin, and proinflammatory cytokines: compounds with nutritional impact in chronic kidney disease? 1468 62

Circulating leptin concentrations are raised in animal models of inflammation and sepsis and leptin production is also increased in rodents by administration of endotoxin or cytokines. The purpose of this study was to investigate the effect of sepsis on serum leptin concentration and whether circulating leptin was related to tumor necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6) release in newborn infants. Plasma leptin, TNF-alpha and IL-6 were measured in 20 neonates with culture-proven sepsis as soon as sepsis was diagnosed and after recovery and in 15 healthy control infants. There was no significant difference in plasma leptin levels between septic and control infants (p > 0.05); there was also no difference in plasma leptin levels in septic neonates before and after therapy (p > 0.05). No relationship between leptin and TNF-alpha (r = 0.16, p > 0.05) or IL-6 (r = 0.12, p > 0.05) was identified. These findings suggest that a major role of leptin in acute neonatal sepsis appears unlikely.
 ...
PMID:Serum leptin levels and their relationship to tumor necrosis factor-alpha and interleukin-6 in neonatal sepsis. 1471 52

At baseline, weight-losing pancreatic cancer patients (n=7) had lower leptin (P<0.05) but higher cortisol, interleukin-6, resting energy expenditure and fat oxidation than healthy subjects (n=6, P<0.05). Over a 4 h feeding period, the areas under the curve for glucose, cortisol and interleukin-6 were greater (P<0.05), but less for leptin in the cancer group (P<0.05). Therefore, it would appear that low leptin concentrations, increased fat oxidation and insulin resistance are associated with increased concentrations of cortisol and interleukin-6 in weight-losing patients with pancreatic cancer.
 ...
PMID:The response of leptin, interleukin-6 and fat oxidation to feeding in weight-losing patients with pancreatic cancer. 1502 90

That obesity is associated with insulin resistance and type II diabetes mellitus is well accepted. Overloading of white adipose tissue beyond its storage capacity leads to lipid disorders in non-adipose tissues, namely skeletal and cardiac muscles, pancreas, and liver, effects that are often mediated through increased non-esterified fatty acid fluxes. This in turn leads to a tissue-specific disordered insulin response and increased lipid deposition and lipotoxicity, coupled to abnormal plasma metabolic and (or) lipoprotein profiles. Thus, the importance of functional adipocytes is crucial, as highlighted by the disorders seen in both "too much" (obesity) and "too little" (lipodystrophy) white adipose tissue. However, beyond its capacity for fat storage, white adipose tissue is now well recognised as an endocrine tissue producing multiple hormones whose plasma levels are altered in obese, insulin-resistant, and diabetic subjects. The consequence of these hormonal alterations with respect to both glucose and lipid metabolism in insulin target tissues is just beginning to be understood. The present review will focus on a number of these hormones: acylation-stimulating protein, leptin, adiponectin, tumour necrosis factor alpha, interleukin-6, and resistin, defining their changes induced in obesity and diabetes mellitus and highlighting their functional properties that may protect or worsen lipid metabolism.
 ...
PMID:Diabetes, lipids, and adipocyte secretagogues. 1505 36


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>