scholarly journals Effects of prepartum 2,4-thiazolidinedione on insulin sensitivity, plasma concentrations of tumor necrosis factor-α and leptin, and adipose tissue gene expression

2011 ◽  
Vol 94 (11) ◽  
pp. 5523-5532 ◽  
Author(s):  
K.M. Schoenberg ◽  
K.L. Perfield ◽  
J.K. Farney ◽  
B.J. Bradford ◽  
Y.R. Boisclair ◽  
...  
Keyword(s):  
Gene Expression ◽  
Adipose Tissue ◽  
Insulin Sensitivity ◽  
Tumor Necrosis ◽  
Tumor Necrosis Factor Α ◽  
Plasma Concentrations ◽  
Adipose Tissue Gene Expression ◽  
Factor Α ◽  
Necrosis Factor ◽  
Tissue Gene Expression

scholarly journals Metformin reduces lipolysis in primary rat adipocytes stimulated by tumor necrosis factor-α or isoproterenol

2006 ◽  
Vol 37 (1) ◽  
pp. 175-183 ◽  
Author(s):  
Tingting Ren ◽  
Jinhan He ◽  
Hongfeng Jiang ◽  
Luxia Zu ◽  
Shenshen Pu ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Insulin Sensitivity ◽  
Tumor Necrosis Factor ◽  
High Glucose ◽  
Tumor Necrosis ◽  
Tumor Necrosis Factor Α ◽  
Lipolytic Action ◽  
Tnf Α ◽  
Factor Α ◽  
Necrosis Factor

In patients with type 2 non-insulin-dependent diabetes mellitus (NIDDM), the biguanide, metformin, exerts its antihyperglycemic effect by improving insulin sensitivity, which is associated with decreased level of circulating free fatty acids (FFA). The flux of FFA and glycerol from adipose tissue to the blood stream primarily depends on the lipolysis of triacylglycerols in the adipocytes. Adipocyte lipolysis is physiologically stimulated by catecholamine hormones. Tumor necrosis factor-α (TNF-α), a cytokine largely expressed in adipose tissue, stimulates chronic lipolysis, which may be associated with increased systemic FFA and insulin resistance in obesity and NIDDM. In this study, we examined the role of metformin in inhibiting lipolytic action upon various lipolytic stimulations in primary rat adipocytes. Treatment with metformin attenuated TNF-α-mediated lipolysis by suppressing phosphorylation of extracellular signal-related kinase 1/2 and reversing the downregulation of perilipin protein in TNF-α-stimulated adipocytes. The acute lipolytic response to adrenergic stimulation of isoproterenol was also restricted by metformin. A high concentration of glucose in the adipocyte culture promoted the basal rate of glycerol release and significantly enhanced the lipolytic action stimulated by either TNF-α or isoproterenol. Metformin not only inhibits the basal lipolysis simulated by high glucose, but also suppresses the high glucose-enhanced lipolysis response to TNF-α or isoproterenol. The antilipolytic action in adipocytes could be the mechanism by which cellular action by metformin reduces systemic FFA concentration and thus improves insulin sensitivity in obese patients and the hyperglycemic conditions of NIDDM.

Insulin stimulates interleukin-6 and tumor necrosis factor-α gene expression in human subcutaneous adipose tissue

2004 ◽  
Vol 286 (2) ◽  
pp. E234-E238 ◽  
Author(s):  
Rikke Krogh-Madsen ◽  
Peter Plomgaard ◽  
Pernille Keller ◽  
Charlotte Keller ◽  
Bente Klarlund Pedersen
Keyword(s):  
Gene Expression ◽  
Skeletal Muscle ◽  
Adipose Tissue ◽  
Tumor Necrosis Factor ◽  
Skeletal Muscles ◽  
Tumor Necrosis ◽  
Tumor Necrosis Factor Α ◽  
Tnf Α ◽  
Factor Α ◽  
Necrosis Factor

High circulating levels of interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) are found in patients with hyperinsulinemia. Insulin stimulates release of IL-6 from adipocyte cultures, and it stimulates IL-6 gene expression in insulin-resistant, but not control, rat skeletal muscle. In addition, TNF-α may be involved in the pathogenesis of insulin resistance. Therefore, we studied the effect of insulin on IL-6 and TNF-α gene expression in human skeletal muscle and adipose tissue. Nine healthy young volunteers participated in the study. They underwent a 6-h hyperinsulinemic euglycemic clamp at a fixed insulin infusion rate, with blood glucose clamped at fasting level. Blood samples drawn at 0, 1, 2, 3, 4, 5, and 6 h were analyzed for IL-6 and TNF-α. Muscle and fat biopsies, obtained at 0, 2, 4, and 6 h, were analyzed for IL-6 and TNF-α mRNA with real-time PCR. IL-6 mRNA increased 11-, 3-, and 5-fold at 2, 4, and 6 h, respectively, in adipose tissue (ANOVA P = 0.027), whereas there was no significant effect of insulin on skeletal muscles. Plasma IL-6 increased during insulin stimulation. TNF-α mRNA increased 2.4-, 1.4-, and 2.2-fold in adipose tissue (ANOVA P = 0.001) and decreased 0.74-, 0.64-, and 0.68-fold in muscle tissue (ANOVA P = 0.04). Plasma levels of TNF-α were constant. In conclusion, the finding that insulin stimulates IL-6 and TNF-α gene expression in adipose tissue only and inhibits the TNF-α production in skeletal muscles suggests a differential regulation of muscle- and adipose tissue-derived IL-6 and TNF-α.

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