Insulin-dependent cytoplasmic distribution of Rab4a in mouse adipocytes is inhibited by interleukin-6, -8, and -15

Cell Biol Int. 2017 Apr;41(4):457-463. doi: 10.1002/cbin.10743. Epub 2017 Feb 21.

Abstract

The purpose of the study was to examine the effect of interleukins, IL-6, IL-8, and IL-15, on insulin-mediated redistribution of Rab4a, an early endosome marker, in mouse 3T3-L1 adipocytes. The interleukins did not affect cell viability; however, cell number was slightly but significantly higher in cultures exposed to IL-8 and IL-15. IL-8 and IL-15 decreased lipid storage in adipocytes, whereas IL-6 had no effect. Rab4A showed cytoplasmic localization, and in control unstimulated adipocytes it was found primarily nearby nucleus, that was supported by cellular fluorescence distribution profile, and by calculated indices, that is, high percentage of near-nuclear area fluorescence and a low mean peripheral cytoplasmic fluorescence/mean near-nuclear fluorescence ratio. Insulin stimulation (100 nmol/l, 30 min) altered the cytoplasmic localization of Rab4a in control adipocytes, which was manifested by its redistribution towards plasma membrane. This effect of insulin was prevented in adipocytes exposed to IL-6, IL-8, or IL-15. We concluded that insulin-dependent Rab4a redistribution, probably reflecting stimulation of vesicle-mediated transport, is inhibited in adipocytes subjected to differentiation in the presence of IL-6, IL-8, or IL-15. Such alterations may be involved in the mechanisms contributing to development of insulin resistance associated with inflammation; however, further studies in this field are required.

Keywords: adipocytes; cytokines; insulin; vesicle-mediated transport.

MeSH terms

  • 3T3-L1 Cells
  • Adipocytes / enzymology*
  • Animals
  • Cytoplasm / enzymology
  • Insulin / physiology*
  • Interleukin-15 / physiology
  • Interleukin-6 / physiology*
  • Interleukin-8 / physiology*
  • Mice
  • Protein Transport
  • rab4 GTP-Binding Proteins / metabolism*

Substances

  • Insulin
  • Interleukin-15
  • Interleukin-6
  • Interleukin-8
  • rab4 GTP-Binding Proteins