Selective Suppression of Adipose Tissue ApoE Expression Impacts Systemic Metabolic Phenotype and Adipose Tissue Inflammation.

Journal of lipid research

PubMedID: 25421060

Huang ZH, Reardon CA, Getz GS, Maeda N, Mazzone T. Selective Suppression of Adipose Tissue ApoE Expression Impacts Systemic Metabolic Phenotype and Adipose Tissue Inflammation. J Lipid Res. 2014;.
ApoE is a multi functional protein expressed in several cell types and in several organs. It is highly expressed in adipose tissue where it is important for modulating adipocyte lipid flux and gene expression in isolated adipocytes. In order to investigate a potential systemic role for apoE that is produced in adipose tissue, mice were generated with selective suppression of adipose tissue apoE expression and normal circulating apoE level. These mice had less adipose tissue with smaller adipocytes containing less lipid, but no change in adipocyte number, compared to control mice. Adipocyte triglyceride synthesis in the presence of apoE-containing VLDL was markedly impaired. Adipocyte caveolin and leptin gene expression were reduced but adiponectin, PGC-1 and CPT-1 gene expression were increased. Mice with selective suppression of adipose tissue apoE had lower fasting lipid, insulin and glucose levels, and glucose tolerance and insulin tolerance tests were consistent with increased insulin sensitivity. Lipid storage in muscle, heart and liver was significantly reduced. Adipose tissue macrophage inflammatory activation was markedly diminished with suppression of adipose tissue apoE expression. Our results establish a novel effect of adipose tissue apoE expression, distinct from circulating apoE, on systemic substrate metabolism and adipose tissue inflammatory state.