IL-6 induces lipolysis and mitochondrial dysfunction, but does not affect insulin-mediated glucose transport in 3T3-L1 adipocytes

J Bioenerg Biomembr. 2011 Aug;43(4):367-75. doi: 10.1007/s10863-011-9361-8. Epub 2011 Jul 6.


Interleukin-6 (IL-6) has emerged as an important cytokine involved in the regulation of metabolism. However, the role of IL-6 in the etiology of obesity and insulin resistance is not fully understood. Mitochondria are key organelles of energy metabolism, and there is growing evidence that mitochondrial dysfunction plays a crucial role in the pathogenesis of obesity-associated insulin resistance. In this study, we determined the direct effect of IL-6 on lipolysis in adipocytes, and the effects of IL-6 on mitochondrial function were investigated. We found that cells treated with IL-6 displayed fewer lipids and an elevated glycerol release rate. Further, IL-6 treatment led to decreased mitochondrial membrane potential, decreased cellular ATP production, and increased intracellular ROS levels. The mitochondria in IL-6-treated cells became swollen and hollow with reduced or missing cristae. However, insulin-stimulated glucose transport was unaltered. PGC-1α, NRF1, and mtTFA mRNA levels were markedly increased, and the mitochondrial contents were also increased. Our results demonstrate that IL-6 can exert a direct lipolytic effect and induce mitochondrial dysfunction. However, IL-6 did not affect insulin sensitivity in adipocytes in vitro. We deduce that in these cells, enhanced mitochondrial biogenesis might play a compensatory role in glucose transport.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3T3-L1 Cells
  • Adipocytes / drug effects*
  • Adipocytes / metabolism
  • Animals
  • Biological Transport
  • Cell Culture Techniques
  • Drug Interactions
  • Glucose / metabolism*
  • Glucose Transport Proteins, Facilitative / metabolism*
  • Insulin / pharmacology*
  • Interleukin-6 / metabolism
  • Interleukin-6 / pharmacology*
  • Lipolysis / drug effects*
  • Mice
  • Mitochondria / drug effects*
  • Mitochondria / metabolism
  • Reactive Oxygen Species / metabolism


  • Glucose Transport Proteins, Facilitative
  • Insulin
  • Interleukin-6
  • Reactive Oxygen Species
  • Glucose