Work

The mRNA‐Binding Protein Zfp36 Is Upregulated by β‐Adrenergic Stimulation and Represses IL‐6 Production in 3T3‐L1 Adipocytes

Year: 2011

Type: article

Abstract: Obesity produces a chronic inflammatory state that contributes to the development of diabetes and atherosclerosis. In obese humans, fat depot adipocytes and macrophages produce inflammatory cytokines and other factors which exert unfavorable local and systemic immune responses. The expression of many cytokines is modulated at the post-transcriptional level by mRNA-binding proteins which recognize AU-rich elements (AREs) in the 3'-untranslated regions (3'-UTR) of these transcripts. One such protein, zinc finger protein 36 (Zfp36), is known to destabilize target mRNAs leading to decreased cytokine expression. Few regulators of Zfp36 expression in adipocytes have been described and mRNA targets of Zfp36 in adipocytes are largely unknown. We found that macrophage-derived inflammatory stimuli enhanced endogenous Zfp36 expression in 3T3-L1 adipocytes. Furthermore, the β-adrenergic receptor agonist isoproterenol (Iso) and the glucocorticoid dexamethasone (Dex) each enhanced Zfp36 expression in adipocytes, the former most likely via a cyclic adenosine monophosphate (cAMP)-dependent pathway. By contrast, Zfp36 expression in murine macrophages (RAW 264.7) was not enhanced by exposure to Dex but was stimulated by retinoic acid (RA). Zfp36 inhibited basal and lipopolysaccharide (LPS)-stimulated interleukin-6 (IL-6) expression in adipocytes. These data reveal important and cell type-specific modulators of Zfp36 expression in adipocytes and macrophages and identify Zfp36 as a potent repressor of adipocyte-derived IL-6. Furthermore, this work identifies new factors that stimulate adipocyte Zfp36 expression that are neither classically inflammatory nor mitogenic. Upregulating an mRNA-binding protein for therapeutic purposes may provide a novel mechanistic approach with which to treat diverse inflammatory disorders including common conditions associated with obesity.

Source: Obesity

DOI: 10.1038/oby.2011.259