Regulation of haptoglobin gene expression in 3T3-L1 adipocytes by cytokines, catecholamines, and PPARgamma.
Factors which regulate expression of the haptoglobin (acute phase reactant) gene in adipocytes have been examined using 3T3-L1 cells. Haptoglobin expression was observed by Northern blotting in each of the major white adipose tissue depots of mice (epididymal, subcutaneous, mesenteric, and perirenal) and in interscapular brown fat. Expression occurred in mature adipocytes, but not in the stromal-vascular fraction. In 3T3-L1 cells, haptoglobin mRNA was detected from day 4 after the induction of differentiation into adipocytes. Lipopolysaccharide and the cytokines, TNFalpha and interleukin-6, resulted in substantial increases in haptoglobin mRNA in 3T3-L1 adipocytes; the increase (7-fold) was highest with TNFalpha. Increases in haptoglobin mRNA level were also induced by dexamethasone, noradrenaline, isoprenaline, and a beta3-adrenoceptor agonist. In contrast, haptoglobin mRNA was reduced by nicotinic acid and the PPARgamma agonist, rosiglitazone. RT-PCR showed that the haptoglobin gene was expressed in human adipose tissue (subcutaneous, omental). It is concluded that haptoglobin gene expression in adipocytes is stimulated by inflammatory cytokines, glucocorticoids, and the sympathetic system, while activation of the PPARgamma nuclear receptor is strongly inhibitory.
do Nascimento
Claudia Oller
CO
Liverpool Centre for Nutritional Genomics, Neuroendocrine and Obesity Biology Unit, Department of Medicine, University of Liverpool, University Clinical Departments, Duncan Building, Liverpool L69 3GA, UK.
Hunter
Leif
L
Trayhurn
Paul
P
D041721:3T3-L1 Cells / Q000378:metabolism*; D017667:Adipocytes / Q000378:metabolism; D000273:Adipose Tissue / Q000378:metabolism; D000316:Adrenergic alpha-Agonists / Q000494:pharmacology; D058667:Adrenergic beta-3 Receptor Agonists; D000318:Adrenergic beta-Agonists / Q000494:pharmacology; D000818:Animals; D015152:Blotting, Northern; D002395:Catecholamines / Q000378:metabolism*; D016207:Cytokines / Q000378:metabolism*; D003907:Dexamethasone / Q000494:pharmacology; D005786:Gene Expression Regulation; D005938:Glucocorticoids / Q000494:pharmacology; D006242:Haptoglobins / Q000096:biosynthesis* / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D007545:Isoproterenol / Q000494:pharmacology; D008070:Lipopolysaccharides / Q000378:metabolism; D051379:Mice; D008820:Mice, Obese; D041681:NIH 3T3 Cells; D009638:Norepinephrine / Q000494:pharmacology; D016376:Oligonucleotides, Antisense / Q000378:metabolism; D012313:RNA / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D018160:Receptors, Cytoplasmic and Nuclear / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013997:Time Factors; D014018:Tissue Distribution; D014157:Transcription Factors / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D014466:Ultraviolet Rays
D000316:Adrenergic alpha-Agonists; D058667:Adrenergic beta-3 Receptor Agonists; D000318:Adrenergic beta-Agonists; D002395:Catecholamines; D016207:Cytokines; D005938:Glucocorticoids; D006242:Haptoglobins; D015850:Interleukin-6; D008070:Lipopolysaccharides; D016376:Oligonucleotides, Antisense; D012333:RNA, Messenger; D018160:Receptors, Cytoplasmic and Nuclear; D014157:Transcription Factors; D014409:Tumor Necrosis Factor-alpha; D012313:RNA; D003907:Dexamethasone; D007545:Isoproterenol; D009638:Norepinephrine