Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P56851 (epididymal)
 11,273 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Obesity is associated with inflammation and increased expression of suppressor of cytokine signaling (SOCS) proteins, which inhibit cytokine and insulin signaling. Thus, reducing SOCS expression could prevent the development of obesity-induced insulin resistance. Using SOCS-1 knockout mice, we investigated the contribution of SOCS-1 in the development of insulin resistance induced by a high-fat diet (HFD). SOCS-1 knockout mice on HFD gained 70% more weight, displayed a 2.3-fold increase in epididymal fat pads mass and increased hepatic lipid content. This was accompanied by increased mRNA expression of leptin and the macrophage marker CD68 in white adipose tissue and of SREBP1c and FAS in liver. HFD also induced hyperglycemia in SOCS-1 deficient mice with impairment of glucose and insulin tolerance tests. Thus, despite the role of SOCS proteins in obesity-related insulin resistance, SOCS-1 deficiency alone is not able to prevent insulin resistance induced by a diet rich in fat.
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PMID:SOCS-1 deficiency does not prevent diet-induced insulin resistance. 1892 39

Interleukin-(IL)6 is the most prominent circulating cytokine induced by systemic infection and inflammation, and the main humoral mediator to the brain in fever. We have previously demonstrated that the PG-pathway, the ultimate step in fever generation, is activated by circulating IL-6 by triggering the expression of the rate limiting enzyme cyclooxygenase (COX)2 in the brain. Downstream of COX2, another enzyme, microsomal PG synthase (mPGES)-1 has also been implicated in the inflammatory response but relatively little is known about its role in cytokine mediated inflammation. Here, we investigated for the first time the direct role of circulating IL-6 in brain and peripheral mPGES-1-expression. Rats were either treated with LPS into a subcutaneous air pouch combined with intraperitoneal injection of a rat specific IL-6 antiserum (AS) or received a single intraperitoneal injection of IL-6. LPS increased the expression of mPGES-1 mRNA in the brain, liver and brown adipose tissue (BAT) but not epididymal white (eW) adipose tissue. This response was reversed by IL-6AS in LPS-injected animals for the brain and liver. IL-6-treatment only induced mPGES-1-expression in the brain and its immunoreactivity co-localized with phosphorylated signal transducer and activator of transcription (STAT)3 the main transcription factor activated by IL-6. Moreover, circulating IL-6 levels and the suppressor of cytokine signaling (SOCS)-3, a broadly used marker of STAT3-activation, strongly correlated with mPGES-1 expression in the brain. In summary, we have clearly shown that circulating IL-6 can directly induce mPGES-1 linked to STAT3-activation in the brain but not peripheral tissues of rats during localised peripheral inflammation.
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PMID:Circulating IL-6 contributes to peripheral LPS-induced mPGES-1 expression in the rat brain. 2194 87

Increased iron stores associated with elevated levels of the iron hormone hepcidin are a frequent feature of the metabolic syndrome. The aim of this study was to assess the effect of dietary iron supplementation on insulin resistance and the role of hepcidin in C57Bl/6 male mice fed a standard or iron-enriched diet for 16 weeks. Iron supplementation increased hepatic iron and serum hepcidin fivefold and led to a 40% increase in fasting glucose due to insulin resistance, as confirmed by the insulin tolerance test, and to threefold higher levels of triglycerides. Iron supplemented mice had lower visceral adipose tissue mass estimated by epididymal fat pad, associated with iron accumulation in adipocytes. Decreased insulin signaling, evaluated by the phospho-Akt/Akt ratio, was detected in the visceral adipose tissue of iron overloaded mice, and gene expression analysis of visceral adipose tissue showed that an iron-enriched diet up-regulated iron-responsive genes and adipokines, favoring insulin resistance, whereas lipoprotein lipase was down-regulated. This resulted in hyperresistinemia and increased visceral adipose tissue expression of suppressor of cytokine signaling-3 (Socs3), a target of resistin and hepcidin implicated in insulin resistance. Acute hepcidin administration down-regulated lipoprotein lipase and up-regulated Socs3 in visceral adipose tissue. In conclusion, we characterized a model of dysmetabolic iron overload syndrome in which an iron-enriched diet induces insulin resistance and hypertriglyceridemia and affects visceral adipose tissue metabolism by a mechanism involving hepcidin up-regulation.
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PMID:Dietary iron overload induces visceral adipose tissue insulin resistance. 2357 84