Interleukin-6 mimics insulin-dependent cellular distribution of some cytoskeletal proteins and Glut4 transporter without effect on glucose uptake in 3T3-L1 adipocytes

Histochem Cell Biol. 2022 May;157(5):525-546. doi: 10.1007/s00418-022-02091-3. Epub 2022 Mar 1.

Abstract

Interleukin (IL)-6, a known proinflammatory cytokine, is released in both visceral adipose tissue and contracting skeletal muscle. In this study, we used microRNA profiling as a screening method to identify miRNA species modified by IL-6 treatment in mouse 3T3-L1 adipocytes. miRNA microarray analysis and qRT-PCR revealed increased expression of miR-146b-3p in adipocytes exposed to IL-6 (1 ng/ml) during 8-day differentiation. On the basis of ontological analysis of potential targets, selected proteins associated with cytoskeleton and transport were examined in the context of adipocyte response to insulin, using immunofluorescence and confocal microscopy. We concluded that IL-6: (i) does not affect insulin action on actin cellular distribution; (ii) modulates the effect of insulin on myosin light chain kinase (Mylk) distribution by preventing its shift toward cytoplasm; (iii) mimics the effect of insulin on dynein distribution by increasing its near-nuclear accumulation; (iv) mimics the effect of insulin on glucose transporter Glut4 distribution, especially by increasing its near-nuclear accumulation; (v) supports insulin action on early endosome marker Rab4A near-nuclear accumulation. Moreover, as IL-6 did not disturb insulin-dependent glucose uptake, our results do not confirm the IL-6-induced impairment of insulin action observed in some in vitro studies, suggesting that the effect of IL-6 is dose dependent.

Keywords: Adipocytes; Cytoskeletal proteins; Glucose uptake; IL-6; MicroRNA; Vesicle transport.

MeSH terms

  • 3T3-L1 Cells
  • Adipocytes / metabolism
  • Animals
  • Cytoskeletal Proteins / metabolism
  • Glucose / metabolism
  • Glucose Transporter Type 4 / metabolism
  • Insulin / metabolism
  • Insulin / pharmacology
  • Interleukin-6* / metabolism
  • Mice
  • MicroRNAs* / metabolism

Substances

  • Cytoskeletal Proteins
  • Glucose Transporter Type 4
  • Insulin
  • Interleukin-6
  • MicroRNAs
  • Glucose