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

The effect of treatment with a 0.03% fatty acid (FA) cocktail on leptin-receptor-mediated STAT (signal transducers and activators of transcription) activation in the rat insulinoma cell line BRIN-BD11 was investigated. Leptin (10 nM) stimulated the tyrosine phosphorylation of STAT3 and STAT5b. Acute treatment with FAs prevented leptin-stimulated STAT3 tyrosine phosphorylation and significantly raised basal STAT5 phosphorylation. A chronic treatment (5 days) of BRIN-BD11 cells with FAs similarly attenuated leptin-stimulated STAT tyrosine phosphorylation. Chronic FA treatment also attenuated prolactin-stimulated STAT5b tyrosine phosphorylation but not interleukin-6-stimulated STAT3 tyrosine phosphorylation, suggesting that the effect is receptor/ligand specific. TaqMan analysis of gene expression following chronic FA treatment showed neither a decrease in the amount of leptin receptor (Ob-R) mRNA, nor an increase in the negative regulators of STAT signalling, SOCS3 (suppressors of cytokine signalling) or cytokine inducible sequence (CIS). These data demonstrate that FAs modulate leptin and prolactin signalling in beta-cells, implying that high levels of circulating FAs present in obese individuals affect the action of selective cytokines in beta-cell function.
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PMID:Fatty acids inhibit leptin signalling in BRIN-BD11 insulinoma cells. 1124 Nov 66

Leptin is involved in the hypothalamic control of food intake and body weight. Fos immunohistochemistry has been used to functionally map leptin target neurons involved in these regulatory processes. However, only a subset of hypothalamic neurons expressing the long form of the leptin receptor (Ob-Rb) also coexpress the neuronal activation marker Fos after leptin stimulation. To functionally map all leptin target neurons, regardless of whether leptin-mediated neuronal activation or inhibition occurs, we immunohistochemically investigated the leptin-induced nuclear translocation of the signal transducer and activator of transcription molecule STAT3, which represents a crucial step in the regulation of leptin-dependent gene expression. As proven by colocalization studies with the nuclear 4',6-diamidino-2-phenylindole dilactate stain, intracerebroventricular leptin treatment, but not intracerebroventricular application of pyrogen-free saline, induced a time-dependent nuclear translocation of STAT3 immunoreactivity in hypothalamic nuclei, with strong nuclear STAT3 signals detectable in the arcuate nucleus, the lateral hypothalamus, and the ventromedial and dorsomedial hypothalamic nuclei. This leptin-induced STAT3 translocation pattern proved to be distinct from that induced by interleukin-6, another cytokine using STAT3 in its signaling pathway. Combined immunohistochemical STAT3 and Fos detection after leptin treatment revealed a higher number of STAT3-positive than Fos-positive cell nuclei in the aforementioned hypothalamic structures and showed that Fos immunoreactivity colocalized only in a subset of all leptin-responsive STAT3 nuclei. These results suggest that the detection of nuclear STAT3 immunoreactivity represents a new neuroanatomical tool to functionally map central leptin actions. They further support the importance of ventrally located caudal hypothalamic structures representing the main leptin targets involved in body weight regulation.
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PMID:Leptin-induced nuclear translocation of STAT3 immunoreactivity in hypothalamic nuclei involved in body weight regulation. 1126 15

Pituitary folliculostellate (FS) cells are usually located between the secretory cells in the anterior pituitary, and they produce many peptides that exert a paracrine effect on hormone-producing pituitary cells. Previous approaches have been unsuccessful in obtaining homogeneous populations of FS cells. We used a combination of immunostaining with S100 protein followed by laser capture microdissection (Immuno-LCM) to obtain purified populations of rat FS cells. These cells were analyzed along with a mouse FS cell line (TtT/GF) by RT-PCR for gene expression. RT-PCR analyses showed that both FS cell populations expressed the mRNAs for glial fibrillary acidic protein, S100 protein, transforming growth factor-beta1 (TGFbeta1), TGFbeta receptor, interleukin-6, leptin, leptin receptor, pituitary adenylate cyclase-activating polypeptide (PACAP), and PACAP receptors. Both FS cell populations were negative for PRL, GH, and POMC, supporting the homogeneity of the rat FS cell population. TGFbeta1, but not PACAP-38, treatment stimulated cell proliferation in both FS cell populations. TGFbeta1 increased leptin, but not interleukin-6, mRNA expression in rat FS cells. However, TGFbeta1 inhibited leptin RNA expression in the TtT/GF cell line, as shown by RT-PCR and Northern blot analysis. These results indicate that 1) homogeneous populations of FS cells can be prepared by Immuno-LCM; 2) TGFbeta1 stimulates the proliferation of normal rat FS cells and the TtT/GF cell line; and 3) the effects of TGFbeta1 to stimulate leptin mRNA expression in rat FS cells but inhibit leptin mRNA expression in TtT/GF cells probably reflect alterations in signal transduction in the TtT/GF cell line.
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PMID:Analysis of homogeneous populations of anterior pituitary folliculostellate cells by laser capture microdissection and reverse transcription-polymerase chain reaction. 1131 32

The ability to ensure continuous availability of energy despite highly variable supplies in the environment is a major determinant of the survival of all species. In higher organisms, including mammals, the capacity to efficiently store excess energy as triglycerides in adipocytes, from which stored energy could be rapidly released for use at other sites, was developed. To orchestrate the processes of energy storage and release, highly integrated systems operating on several physiological levels have evolved. The adipocyte is no longer considered a passive bystander, because fat cells actively secrete many members of the cytokine family, such as leptin, tumor necrosis factor-alpha, and interleukin-6, among other cytokine signals, which influence peripheral fuel storage, mobilization, and combustion, as well as energy homeostasis. The existence of a network of adipose tissue signaling pathways, arranged in a hierarchical fashion, constitutes a metabolic repertoire that enables the organism to adapt to a wide range of different metabolic challenges, such as starvation, stress, infection, and short periods of gross energy excess.
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PMID:The adipocyte: a model for integration of endocrine and metabolic signaling in energy metabolism regulation. 1135 Jul 65

Human adipose tissue has an important protein secretory function. Cytokines, hormones, prohormones and enzymes are secreted from fat cells and act in an endocrine or paracrine fashion. The production of several of these proteins is affected by obesity; normally there is an increase in the obese state. Protein production is, as a metabolic activity, subject to regional variations. In particular, the production of leptin, angiotensinogen, interleukin-6 and plasmin activator inhibitor-1 differs between subcutaneous and visceral adipose tissue sites, but no regional differences have been reported in the production of tumour necrosis factor alpha. It is possible that regional variations in protein production by adipose tissue are of importance in some of the endocrine and metabolic disturbances seen in various forms of obesity, such as visceral and upper-body obesity.
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PMID:Regional differences in protein production by human adipose tissue. 1135 30

Pfeiffer and colleagues years ago pointed out that different distributions and amounts of adipose tissue are associated with abnormalities of lipolysis and lipoprotein metabolism. Adipose tissue has several crucial roles including (i) mobilization from stores of fatty acids as an energy source, (ii) catabolism of lipoproteins such as very-low-density lipoprotein and (iii) synthesis and release of hormonal signals such as leptin and interleukin-6. These adipose tissue actions are crucially regulated by nutrition. The review considers the existence of metabolic pathways and modes of regulation within adipose tissue, and how such metabolic activity can be quantitated in humans. Nutrition can influence adipose tissue at several 'levels'. Firstly the level of obesity or malnutrition has important effects on many aspects of adipose tissue metabolism. Secondly short-term overfeeding, underfeeding and exercise have major impacts on adipose tissue behaviour. Lastly, specific nutrients are capable of regulating adipose tissue metabolism. Recently there have been considerable advances in understanding adipose tissue metabolism and in particular its regulation. This review discusses the behaviour of adipose tissue under various nutritional conditions. There is then a review of recent work examining the ways in which nutritional influences act via intra-cellular mechanisms, insulin and the sympathetic innervation of adipose tissue.
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PMID:Nutritional regulation of lipid metabolism in human adipose tissue. 1146 May 71

Previous research has shown that reductions in body weight prior to induction of acute inflammation can attenuate inflammation-induced anorexia in male rats. In the current study, potential mechanisms responsible for this observation were examined. Specifically, the effect of a 12% prior reduction in body weight on serum leptin, insulin, and corticosterone; levels of interleukin-1 (IL-1), interleukin-6 (IL-6) in the serum, liver, and spleen; neuropeptide Y (NPY) and POMC mRNA levels in the arcuate nucleus (ARC) of the hypothalamus were examined 8 h after induction of acute inflammation. Rats with prior weight reduction had significantly lower serum leptin levels and gene expression of POMC in the ARC than normal-weight rats. In contrast, prior weight reduction altered neither NPY mRNA in the ARC, nor IL-1alpha, IL-1beta, and IL-6 levels in the serum, liver, and spleen. These results suggest that the attenuation of inflammation-induced anorexia by prior weight reduction is not due to altered cytokine activity, but rather to changes in energy regulatory systems that moderate the anorexic actions of IL-1beta and IL-6. One potential change may be reduced activity of the CNS melanocortin system induced by decreased circulating leptin.
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PMID:Activity of body energy regulatory pathways in inflammation-induced anorexia. 1149 55

Endothelial cells and fibroblasts are important constituents of the haemopoietic microenvironment. Growth and function of these cells are controlled by a variety of cytokines, including vascular endothelial growth factor (VEGF) and platelet-derived growth factor (PDGF). We analysed the effects of novel tyrosine kinase inhibitors targeting the VEGF and PDGF receptors (compounds SU5614 and SU5768) on the performance of long-term cultures from normal human bone marrow. In developing cultures, the inhibitors induced a dose-dependent reduction in stromal fibroblasts, macrophages and endothelial cells with a concomitant decrease in blood cell production and an increase in fat cells. For SU5614, the concentration inhibiting stroma formation by 50% (IC50) was 123nM, and the IC50 for haemopoietic colony forming cell output was 186 nM. For SU5768, the respective values were 871 nM and 331 nM. Changes in stroma composition and inhibition of haemopoietic cell production were also demonstrable after delayed addition of the inhibitors to established cultures. By contrast, haemopoietic colony formation in clonogenic agar cultures was unimpaired (IC50 not reached at 100 microM). Immunofluorescence studies and time course analyses suggested that the primary effect of the inhibitors was interference with the proliferation and function of fibroblasts and endothelial cells which in turn resulted in decreased haemopoiesis and increased adipogenesis. This was associated with decreased levels in conditioned media of granulocyte-macrophage colony-stimulating factor, interleukin-6 and leptin. VEGF and PDGF may play a hitherto underestimated role in the control of blood cell formation. VEGF/PDGF receptor inhibitors may have therapeutic potential in stroma diseases such as myelofibrosis. Since they weaken the stimulatory signals provided by the microenvironment, they may also be of value in the treatment of leukaemia and other neoplastic bone marrow diseases.
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PMID:Effects of vascular endothelial and platelet-derived growth factor receptor inhibitors on long-term cultures from normal human bone marrow. 1167 6

Weight loss is typically found during severe infections, e.g. septic arthritis. The aim of our study was to evaluate the role of leptin, regulator of food intake and energy expenditure, for the development of Staphylococcus aureus-triggered arthritis. Leptin production was found to be decreased during murine S. aureus-induced arthritis. Treatment with recombinant leptin neither restored the basal leptin levels nor affected the weight loss during the disease, but it significantly decreased the severity of septic arthritis. Exogenous leptin did not affect the staphylococcal load as measured in blood, joints and kidneys. Preceding the effects on joint manifestations, serum levels of interleukin-6 decreased in leptin-treated mice. In conclusion, the treatment with recombinant leptin reduced both the severity of joint manifestations in S.aureus-induced arthritis and the inflammatory response, as measured by serum IL-6 levels, without affecting the survival of bacteria in vivo.
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PMID:Leptin in septic arthritis: decreased levels during infection and amelioration of disease activity upon its administration. 1171 94

Acute release of corticotropin-releasing factor (CRF) during repeated restraint (3-h restraint on each of 3 days) causes temporary hypophagia but chronic suppression of body weight in rats. Here we demonstrated that a second bout of repeated restraint caused additional weight loss, but continuing restraint daily for 10 days did not increase weight loss because the rats adapted to the stress. In these two studies serum leptin, which suppresses the endocrine response to stress, was reduced in restrained rats. Peripheral infusion of leptin before and during restraint did not prevent stress-induced weight loss, although stress-induced corticosterone release was suppressed. Restrained rats were hyperthermic during restraint, but there was no evidence that fever or elevated free interleukin-6 caused the sustained reduction in weight. Restraining food-restricted rats caused a small but significant weight loss. Food-restricted rats fed ad libitum after the end of restraint showed a blunted hyperphagia and slower rate of weight regain than their controls. These results indicate that repeated acute stress induces a chronic change in weight independent of stress-induced hypophagia and may represent a change in homeostasis initiated by repeated acute activation of the central CRF system.
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PMID:Weight loss in rats exposed to repeated acute restraint stress is independent of energy or leptin status. 1174 26


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