Iron Inhibits the Secretionof Apolipoprotein E in Cultured Human Adipocytes.

Abstract

Nonalcoholic steatohepatitis (NASH) is characterized by adipose tissue dysfunction with insulin resistance and the dysregulation of adipokines.1 Recent data indicate repartitioning of iron from the liver to adipocytes in obesity and a role for iron in the development of adipose tissue dysfunction.2, 3 However, the molecular mechanisms have not been established. To test the hypothesis that iron modulates adipokine release, we performed a quantitative proteomics analysis of the human Simpson-Golabi-Behmel Syndrome (SGBS) adipocyte secretome after 48 hours of treatment with ferric ammonium citrate (FAC). We used stable isotope-labeled amino acids in cell culture (SILAC) to characterize changes in the adipocyte secretome in response to iron. This technique has enabled direct comparison of quantities of individual proteins in the adipocyte secretome in response to iron using a proteomics approach as a tool for the identification of novel treatment targets in NASH. Detailed methodology is described in Supplementary Methods...