Mohamed-Ali, V and Flower, L and Sethi, J and Hotamisligil, G and Gray, R and Humphries, SE and York, DA and Pinkney, J (2001) beta-adrenergic regulation of IL-6 release from adipose tissue: In vivo and in vitro studies. J CLIN ENDOCR METAB , 86 (12) 5864 - 5869.
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Circulating IL-6 levels are elevated in obesity. Although IL-6 is expressed in adipose tissue, neither its regulation nor cell of origin is well characterized. Here we investigated the beta -adrenergic regulation of IL-6 release in a combination of studies on humans and sn im als in vivo and cultured adipocytes in vitro. Human in vivo study: Human volunteers were infused with isoproterenol, norepinephrine, or saline (4 m:4F; mean (SD) age 35.5 (5.8) yr; body mass index 24.6 (4.2) kg/m(-2)]. Plasma IL-6 levels increased during a 3-h infusion of isoproterenol (P = 0.01) and fell 2 h post infusion (P = 0.05). IL-6 levels did not change significantly with either norepinephrine or saline. Murine in vivo study: C57BL6/J male mice were injected ip with dobutamine (beta (1) agonist), clenbuterol. (beta (2)), CL316243 (beta (3)), or saline, placebo. Plasma IL-6 levels at 3 h were increased by clenbuterol (P = 0.02) and CL316243 (P = 0.02) but not dobutamine (P = 0.51), compared with placebo. In vitro studies: In human peripheral blood cells, lipopolysaccharide treatment enhanced secretion of IL-6 (vs. controls; P < 0.001), whereas isoproterenol inhibited IL-6 secretion (P = 0.012) and norepinephrine had no significant effect. In contrast, isolated human adipocytes and differentiated 3T3F442A adipocytes all rapidly secreted IL-6 in response to adrenergic agonists (P < 0.01, compared with untreated cells). We conclude that beta2/beta3 adrenoceptor stimulation on adipocytes, rather than macrophages, may be responsible for the increases in plasma IL-6 concentrations observed during sympathetic activation and in obesity.
|Title:||beta-adrenergic regulation of IL-6 release from adipose tissue: In vivo and in vitro studies|
|Keywords:||TUMOR-NECROSIS-FACTOR, RECOMBINANT HUMAN INTERLEUKIN-6, CULTURED RAT HEPATOCYTES, PITUITARY-ADRENAL AXIS, PLASMA INTERLEUKIN-6, GLUCOSE-TRANSPORT, 3T3-L1 ADIPOCYTES, GENE-EXPRESSION, SECRETION, CELLS|
|UCL classification:||UCL > School of Life and Medical Sciences > Faculty of Medical Sciences > Medicine (Division of)|
UCL > School of Life and Medical Sciences > Faculty of Population Health Sciences > Institute of Cardiovascular Science
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