1. Regulation of haptoglobin gene expression in 3T3-L1 adipocytes by cytokines, catecholamines, and PPARgamma.
- Author
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do Nascimento CO, Hunter L, and Trayhurn P
- Subjects
- Adipocytes metabolism, Adipose Tissue metabolism, Adrenergic alpha-Agonists pharmacology, Adrenergic beta-3 Receptor Agonists, Adrenergic beta-Agonists pharmacology, Animals, Blotting, Northern, Dexamethasone pharmacology, Glucocorticoids pharmacology, Haptoglobins metabolism, Interleukin-6 metabolism, Isoproterenol pharmacology, Lipopolysaccharides metabolism, Mice, Mice, Obese, NIH 3T3 Cells, Norepinephrine pharmacology, Oligonucleotides, Antisense metabolism, RNA metabolism, RNA, Messenger metabolism, Reverse Transcriptase Polymerase Chain Reaction, Time Factors, Tissue Distribution, Tumor Necrosis Factor-alpha metabolism, Ultraviolet Rays, 3T3-L1 Cells metabolism, Catecholamines metabolism, Cytokines metabolism, Gene Expression Regulation, Haptoglobins biosynthesis, Receptors, Cytoplasmic and Nuclear metabolism, Transcription Factors metabolism
- Abstract
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.
- Published
- 2004
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