Effects of NYGGF4 knockdown on insulin sensitivity and mitochondrial function in 3T3-L1 adipocytes

J Bioenerg Biomembr. 2010 Oct;42(5):433-9. doi: 10.1007/s10863-010-9313-8. Epub 2010 Nov 16.

Abstract

NYGGF4 is a recently discovered gene that is involved in obesity-associated insulin resistance. It has been suggested that mitochondrial dysfunction might be responsible for the development of insulin resistance induced by NYGGF4 overexpression. In the present study, we aimed to define the impact of down-regulating NYGGF4 expression by RNA interference (RNAi) on the insulin sensitivity and mitochondrial function of 3T3-L1 adipocytes. The results revealed that NYGGF4 knockdown enhanced the glucose uptake of adipocytes, which reconfirmed the regulatory function of NYGGF4 in adipocyte insulin sensitivity. However, an unexpected observation was that knockdown of NYGGF4 reduced intracellular ATP concentration and promoted an increase in mitochondrial transmembrane potential (ΔΨm) and reactive oxygen species (ROS) level without affecting mitochondrial morphology or mtDNA. Therefore, the role of NYGGF4 in mitochondrial function remains unclear, and further animal studies are needed to explore the biological function of this gene.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3T3-L1 Cells
  • Adipocytes / metabolism*
  • Adipocytes / physiology
  • Adipocytes / ultrastructure
  • Analysis of Variance
  • Animals
  • Carrier Proteins / genetics*
  • DNA Primers / genetics
  • DNA, Complementary / genetics
  • Gene Knockdown Techniques
  • Glucose / metabolism
  • Insulin Resistance / genetics*
  • Membrane Potential, Mitochondrial / physiology
  • Mice
  • Microscopy, Electron
  • Mitochondria / genetics*
  • Mitochondria / physiology
  • Plasmids / genetics
  • RNA, Small Interfering / genetics
  • Reactive Oxygen Species / metabolism
  • Reverse Transcriptase Polymerase Chain Reaction
  • Transfection

Substances

  • Carrier Proteins
  • DNA Primers
  • DNA, Complementary
  • NYGGF4 protein, mouse
  • RNA, Small Interfering
  • Reactive Oxygen Species
  • Glucose