ADP-ribosylation factor 6 modulates adrenergic stimulated lipolysis in adipocytes

Yingqiu Liu, Dequan Zhou, Nada A. Abumrad, Xiong Su

Research output: Contribution to journalArticlepeer-review

19 Scopus citations

Abstract

ADP-ribosylation factor 6 (Arf6) is a small GTPase that influences membrane receptor trafficking and the actin cytoskeleton. In adipocytes, Arf6 regulates the trafficking of the glucose transporter type 4 (GLUT4) and consequently insulin-stimulated glucose transport. Previous studies also indicated a role of Arf6 in adrenergic receptor trafficking, but whether this contributes to the control of lipolysis in adipocytes remains unknown. This was examined in the present study by using RNA interference (RNAi) and pharmaceutical inhibition in murine cultured 3T3-L1 adipocytes. Downregulation of Arf6 by RNAi impairs isoproterenol-stimulated lipolysis specifically but does not alter triacylglycerol (TAG) synthesis or the insulin signaling pathway. Neither total TAG amounts nor TAG fatty acid compositions are altered. The inhibitory effect on lipolysis is mimicked by dynasore, a specific inhibitor for dynamin, which is required for endocytosis. In contrast, lipolysis triggered by reagents that bypass events at the plasma membrane (e.g., forskolin, isobutylmethylxanthine or 8-bromo-cAMP) is not affected. Moreover, Arf6 protein levels in white adipose tissues are markedly increased in ob/ob mice, whereas they are decreased in obesity-resistant CD36 null mice. These changes reflect at least in part alterations in Arf6 mRNA levels. Collectively, these results suggest a role of the endocytic pathway and its regulation by Arf6 in adrenergic stimulation of lipolysis in adipocytes and potentially in the development of obesity.

Original languageEnglish
Pages (from-to)C921-C928
JournalAmerican Journal of Physiology - Cell Physiology
Volume298
Issue number4
DOIs
StatePublished - Apr 2010

Keywords

  • Trafficking
  • β-adrenergic receptor

Fingerprint

Dive into the research topics of 'ADP-ribosylation factor 6 modulates adrenergic stimulated lipolysis in adipocytes'. Together they form a unique fingerprint.

Cite this