Isoproterenol is a positive regulator of the suppressor of cytokine signaling-3 gene expression in 3T3-L1 adipocytes

Faßhauer, Mathias; Klein, Johannes; Lössner, Ulrike; Paschke, Ralf

doi:10.1677/joe.0.1750727

Cited by 23 publications

(17 citation statements)

References 39 publications

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“…They include upregulation of IRS-1, the p85 subunit of phosphatidylinositol 3-kinase (PI3-kinase), thymoma viral proto-oncoprotein (Akt), growth factor receptor-bound protein 2 (Grb2), growth factor receptorbound protein 10 (Grb10), and extracellular signal-regulated kinase 1 (Erk1) and downregulation of SOCS3, an inhibitor of insulin signaling. It has been shown that activation of the PI3K/ Akt pathway is required for insulin-induced adipogenesis (1,34,58,60), while adipocyte differentiation is associated with downregulation of SOCS3 expression (12). Thus, the coordinated regulation of insulin signaling components by BMP7 suggests that BMP7-induced adipogenesis is mediated at least partly by enhancing insulin signaling.…”

Section: Bmp7 Induces Expression Of Insulin Signaling Components In Mmentioning

confidence: 99%

Cross Talk between Insulin and Bone Morphogenetic Protein Signaling Systems in Brown Adipogenesis

Zhang

Schulz

Espinoza

et al. 2010

Molecular and Cellular Biology

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Both insulin and bone morphogenetic protein (BMP) signaling systems are important for adipocyte differentiation. Analysis of gene expression in BMP7-treated fibroblasts revealed a coordinated change in insulin signaling components by BMP7. To further investigate the cross talk between insulin and BMP signaling systems in brown adipogenesis, we examined the effect of BMP7 in insulin receptor substrate 1 (IRS-1)-deficient brown preadipocytes, which exhibit a severe defect in differentiation. Treatment of these cells with BMP7 for 3 days prior to adipogenic induction restored differentiation and expression of brown adipogenic markers. The high level of adipogenic inhibitor preadipocyte factor 1 (Pref-1) in IRS-1-null cells was markedly reduced by 3 days of BMP7 treatment, and analysis of the 1.3-kb pref-1 promoter revealed 9 putative Smad binding elements (SBEs), suggesting that BMP7 could directly suppress Pref-1 expression, thereby allowing the initiation of the adipogenic program. Using a series of sequential deletion mutants of the pref-1 promoter linked to the luciferase gene and chromatin immunoprecipitation, we demonstrate that the promoter-proximal SBE (؊192/؊184) was critical in mediating BMP7's suppressive effect on pref-1 transcription. Together, these data suggest cross talk between the insulin and BMP signaling systems by which BMP7 can rescue brown adipogenesis in cells with insulin resistance.Obesity and insulin resistance are two hallmark features of a larger collection of abnormalities called the metabolic syndrome. It is estimated that over 40 million people in the United States have the metabolic syndrome, and it is this cluster of abnormalities that creates risk for many of our most common medical conditions, including glucose intolerance, dyslipidemias, nonalcoholic fatty liver, cardiovascular disease, renal failure, Alzheimer's disease, and even some cancers (7,8,21,24). Adipose tissue plays an active role in systemic energy metabolism (14) and therefore contributes to the pathogenesis of the metabolic syndrome. There are two functionally different types of adipose tissue: white adipose tissue, which is specialized for the storage of excess energy in the form of triglycerides, and brown adipose tissue, which is completely dedicated to energy expenditure in response to cold or overfeeding. Given its tremendous capacity to dissipate chemical energy (4) and its recently demonstrated presence in adult humans (9,53,32,40,55,62), promoting brown fat differentiation and function provides an attractive approach to the treatment of obesity and related metabolic complications.Adipocyte differentiation is regulated by a network of hormones and growth factors (4, 14). Insulin signaling is known to play a pivotal role in both white and brown adipogenesis (38). Insulin receptor substrates (IRSs) function as the docking proteins coordinating hormone binding to the receptor and downstream signaling events (56). There are four members of the IRS protein family, and each has a unique and complementary function ...

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Section: Bmp7 Induces Expression Of Insulin Signaling Components In Mmentioning

confidence: 99%

Cross Talk between Insulin and Bone Morphogenetic Protein Signaling Systems in Brown Adipogenesis

Zhang

Schulz

Espinoza

et al. 2010

Molecular and Cellular Biology

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“…Our current findings suggest that downregulation of visfatin in adipocytes may contribute to impaired glucose tolerance caused by increased GH levels. However, it has to be pointed out that stimulation of suppressor of cytokine signaling (SOCS)-1 (Fasshauer et al 2004b) and -3 (Fasshauer et al 2002), activation of MCP-1 (Fasshauer et al 2004a) and IL-6 (Fasshauer & Paschke 2003), as well as altered insulin signaling downstream of phosphatidylinositol 3-kinase (Takano et al 2001), are additional mechanisms by which GH affects glucose metabolism.…”

Section: Figurementioning

confidence: 99%

“…In 3T3-L1 adipocytes significant impairment of insulin-stimulated glucose uptake is seen after treatment with 4 µM isoproterenol for 16 h (Kaestner et al 1991). Several mechanisms by which catecholamines induce insulin resistance have been suggested, including molecular interactions on several levels between adrenergic and insulin signaling cascades (Klein et al 1999, Klein et al 2000, upregulation of IL-6 (Fasshauer & Paschke 2003) and SOCS-3 (Fasshauer et al 2002), as well as suppression of adiponectin (Fasshauer & Paschke 2003). Based on the findings in our current study, downregulation of the insulinmimetic visfatin may also contribute to catecholamineinduced glucose intolerance.…”

Section: Figurementioning

confidence: 99%

Hormonal regulation of the novel adipocytokine visfatin in 3T3-L1 adipocytes

Kralisch¹,

Klein²,

Lössner³

et al. 2005

Journal of Endocrinology

148

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Recently, visfatin was characterized as a novel adipocytokine that is upregulated in obesity and exerts insulinmimetic effects in various tissues. To clarify expression and regulation of this adipocytokine, visfatin mRNA was measured by quantitative real-time reverse transcriptionpolymerase chain reaction in 3T3-L1 adipocytes during adipogenesis and after treatment with various hormones known to alter insulin sensitivity. Visfatin expression was about 6-fold higher in 3T3-L1 adipocytes in vitro as compared with epididymal fat in vivo and increased during adipogenic conversion more than 3-fold. Interestingly, 100 nM dexamethasone significantly increased visfatin mRNA by almost 1·5-fold. In contrast, 500 ng/ml growth hormone (GH), 10 ng/ml tumor necrosis factor (TNF) , and 10 µM isoproterenol downregulated visfatin expression by 45%, 36%, and 43% respectively. Insulin did not influence synthesis of this adipocytokine. The effects of dexamethasone, GH, TNF and isoproterenol were time-and dose-dependent. Furthermore, activation of G s -protein-coupled pathways by forskolin and cholera toxin was sufficient to significantly downregulate visfatin mRNA. Taken together, our results show a differential regulation of visfatin mRNA by insulin resistanceinducing hormones, supporting the view that this adipocytokine might be an interesting novel candidate linking core components of the metabolic syndrome such as obesity and insulin resistance.

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“…Recently, we and others have demonstrated that GH, TNF , insulin and -adrenergic agonists stimulate SOCS-3 mRNA expression and that SOCS-3 inhibits insulin signaling in 3T3-L1 adipocytes (Emanuelli et al 2000, 2001, Fasshauer et al 2002. Furthermore, it has been shown that SOCS-1 and -6 are also potent inhibitors of insulin signaling (Mooney et al 2001, Rui et al 2002, and it appears plausible that cytokines such as TNF , GH, and IL-6 might further decrease insulin sensitivity in fat cells by upregulating either of these proteins.…”

Section: Introductionmentioning

confidence: 99%

Insulin resistance-inducing cytokines differentially regulate SOCS mRNA expression via growth factor- and Jak/Stat-signaling pathways in 3T3-L1 adipocytes

Faßhauer

Kralisch²,

Klier³

et al. 2004

Journal of Endocrinology

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Various cytokines, including tumor necrosis factor (TNF) , growth hormone (GH) and interleukin (IL)-6, induce insulin resistance. Recently, it was demonstrated that induction of suppressor of cytokine signaling (SOCS)-3 by TNF and GH is an important mechanism by which these cytokines impair insulin sensitivity. The current study investigated in 3T3-L1 adipocytes whether TNF and GH also upregulate SOCS-1 and SOCS-6, which have both been shown to inhibit insulin signaling potently, and whether IL-6 might alter synthesis of SOCS-1, -3 and -6. Interestingly, 10 ng/ml TNF , 500 ng/ml GH and 30 ng/ml IL-6 induced SOCS-1 mRNA timedependently with maximal stimulation detectable after 8 h of TNF and 1 h of GH and IL-6 addition respectively. Furthermore, TNF and GH caused sustained upregulation of SOCS-1 for up to 24 h, whereas stimulation by IL-6 was only transient, with SOCS-1 mRNA returning to basal levels 2 h after effector addition. Induction of SOCS-1 was dose-dependent, and significant stimulation was detectable at concentrations as low as 3 ng/ml TNF , 50 ng/ml GH and 10 ng/ml IL-6. Furthermore, stimulation experiments and studies using pharmacologic inhibitors suggested that the positive effect of TNF , GH and IL-6 on SOCS-1 mRNA is, at least in part, mediated by Janus kinase (Jak) 2. Finally, SOCS-3 expression was dose-and time-dependently induced by IL-6, at least in part via Jak2, but none of the cytokines affected SOCS-6 expression. Taken together, our results show a differential regulation of SOCS mRNA by insulin resistance-inducing hormones, and suggest that SOCS-1, as well as SOCS-3, may be an important intracellular mediator of insulin resistance in fat cells and a potential pharmacologic target for the treatment of impaired insulin sensitivity.

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Isoproterenol is a positive regulator of the suppressor of cytokine signaling-3 gene expression in 3T3-L1 adipocytes

Cited by 23 publications

References 39 publications

Cross Talk between Insulin and Bone Morphogenetic Protein Signaling Systems in Brown Adipogenesis

Cross Talk between Insulin and Bone Morphogenetic Protein Signaling Systems in Brown Adipogenesis

Hormonal regulation of the novel adipocytokine visfatin in 3T3-L1 adipocytes

Insulin resistance-inducing cytokines differentially regulate SOCS mRNA expression via growth factor- and Jak/Stat-signaling pathways in 3T3-L1 adipocytes

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