title: Apolipoprotein E promotes lipid accumulation and differentiation in human adipocytes.
abstract: Several studies in mice indicate a role for apolipoprotein E (APOE) in lipid accumulation and adipogenic differentiation in adipose tissue. However, little is yet known if APOE functions in a similar manner in human adipocytes. This prompted us to compare lipid loading and expression of adipocyte differentiation markers in APOE-deficient and control adipocytes using the differentiated human mesenchymal stem cell line hMSC-Tert as well as primary human and mouse adipocytes as model systems. Differentiated hMSC-Tert were stably transduced with or without siRNA targeting APOE while murine adipocytes were isolated from wild type and Apoe knockout mice. Human APOE knockdown hMSC-Tert adipocytes accumulated markedly less triglycerides compared to control cells. This correlated with strongly decreased gene expression levels of adipocyte markers such as adiponectin (ADIPOQ) and fatty acid binding protein 4 (FABP4) as well as the key transcription factor driving adipocyte differentiation, peroxisome proliferator activator receptor gamma (PPARG), in particular the PPARG2 isoform. Similarly, differentiation of murine Apoe-deficient adipocytes was characterized by reduced gene expression of Adipoq, Fabp4 and Pparg. Interestingly, incubation of APOE-deficient hMSC-Tert adipocytes with conditioned media from APOE3-overexpressing adipocytes or APOE-containing Very Low Density Lipoprotein (VLDL) partially restored triglyceride accumulation, but were unable to induce adipocyte differentiation, as judged by expression of adipocyte markers. Taken together, depletion of endogenous APOE in human adipocytes severely impairs lipid accumulation, which is associated with an inability to initiate differentiation.
authors.affiliation: Department of Biochemistry and Molecular Cell Biology, University Medical Center Hamburg-Eppendorf, Martinistr. 52, 20246 Hamburg, Germany.
authors.forename: Dorothee
authors.initials: D
authors.lastname: Lasrich
authors.affiliation: Department of Biochemistry and Molecular Cell Biology, University Medical Center Hamburg-Eppendorf, Martinistr. 52, 20246 Hamburg, Germany.
authors.forename: Alexander
authors.initials: A
authors.lastname: Bartelt
authors.affiliation: Faculty of Pharmacy A15, The University of Sydney, Sydney, NSW 2006, Australia. Electronic address: thomas.grewal@sydney.edu.au.
authors.forename: Thomas
authors.initials: T
authors.lastname: Grewal
authors.affiliation: Department of Biochemistry and Molecular Cell Biology, University Medical Center Hamburg-Eppendorf, Martinistr. 52, 20246 Hamburg, Germany. Electronic address: heeren@uke.de.
authors.forename: Joerg
authors.initials: J
authors.lastname: Heeren
mesh_terms: D017667:Adipocytes / Q000502:physiology*; D000818:Animals; D053318:Apolipoprotein E3 / Q000502:physiology*; D002454:Cell Differentiation; D015870:Gene Expression; D006801:Humans; D050356:Lipid Metabolism; D051379:Mice; D008810:Mice, Inbred C57BL
chemical_list: D053318:Apolipoprotein E3
keywords: Adipocyte differentiation; Adipocytes; Apolipoprotein E; Lipoproteins; Peroxisome proliferator activated receptor gamma; Triglycerides