title: Selective suppression of adipose tissue apoE expression impacts systemic metabolic phenotype and adipose tissue inflammation.
abstract: 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.
authors.affiliation: Department of Pathology, University of Chicago, Chicago, IL.
authors.forename: Zhi H
authors.initials: ZH
authors.lastname: Huang
authors.affiliation: Department of Pathology, University of Chicago, Chicago, IL.
authors.forename: Catherine A
authors.initials: CA
authors.lastname: Reardon
authors.affiliation: Department of Pathology, University of Chicago, Chicago, IL.
authors.forename: Godfrey S
authors.initials: GS
authors.lastname: Getz
authors.affiliation: Department of Pathology and Laboratory Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC.
authors.forename: Nobuyo
authors.initials: N
authors.lastname: Maeda
authors.affiliation: Department of Medicine, NorthShore University HealthSystem, Evanston, IL and University of Chicago, Chicago, IL.
authors.forename: Theodore
authors.initials: T
authors.lastname: Mazzone
mesh_terms: D017667:Adipocytes / Q000378:metabolism; D000273:Adipose Tissue / Q000378:metabolism* / Q000473:pathology; D000818:Animals; D001057:Apolipoproteins E / Q000235:genetics* / Q000378:metabolism; D015153:Blotting, Western; D005786:Gene Expression Regulation; D007249:Inflammation / Q000378:metabolism*; D007333:Insulin Resistance / Q000502:physiology; D050356:Lipid Metabolism / Q000502:physiology; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D009765:Obesity / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014280:Triglycerides / Q000378:metabolism
chemical_list: D001057:Apolipoproteins E; D014280:Triglycerides
keywords: apolipoprotein E; apolipoproteins; insulin resistance; lipid metabolism; obesity