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 levels. These mice had less adipose tissue with smaller adipocytes containing fewer
lipids, but no change in adipocyte number compared with control mice. Adipocyte TG 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 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.