ApoE derived from adipose tissue does not suppress atherosclerosis or correct hyperlipidemia in apoE knockout mice.
The synthesis of apoE by adipocytes has profound effects on adipose tissue lipid flux and gene expression. Using adipose tissue transplantation from wild-type (WT) to apoE knockout (EKO) mice, we show that adipose tissue also contributes to circulating apoE. Different from circulating apoE produced by bone marrow transplantation (BMT), however, adipose tissue-derived apoE does not correct hyperlipidemia or suppress atherosclerosis. ApoE secreted by macrophages has a more acidic isoform distribution, and it increases binding of reconstituted VLDL particles to hepatocytes and fibroblasts more effectively than apoE secreted by adipocytes. The incremental binding can be entirely accounted for by binding to the LDL receptor. After BMT into EKO hosts, plasma cholesterol and macrophage-derived apoE are largely within IDL/LDL- and HDL-sized particles. After adipose tissue transplantation, most cholesterol and adipocyte apoE remain in VLDL. After BMT, circulating apoE no longer demonstrates predominance of acidic isoforms compared with that circulating after fat transplantation. In conclusion, fat transplantation provides circulating apoE levels similar to those provided by bone marrow transplantation, but it does not suppress hyperlipidemia or atherosclerosis. A potential mechanism contributing to this difference is differential binding to cell surface lipoprotein receptors.
Department of Medicine, University of Chicago, Chicago, IL, USA.
Zhi H
ZH
Huang
Catherine A
CA
Reardon
Papasani V
PV
Subbaiah
Godfrey S
GS
Getz
Theodore
T
Mazzone
D000273:Adipose Tissue / Q000166:cytology / Q000378:metabolism*; D000818:Animals; D001057:Apolipoproteins E / Q000096:biosynthesis* / Q000097:blood / Q000172:deficiency / Q000235:genetics*; D050197:Atherosclerosis / Q000097:blood / Q000378:metabolism* / Q000473:pathology / Q000601:surgery; D001692:Biological Transport; D016026:Bone Marrow Transplantation; D002784:Cholesterol / Q000378:metabolism; D017077:Culture Media, Conditioned / Q000378:metabolism; D055786:Gene Knockout Techniques; D006949:Hyperlipidemias / Q000097:blood / Q000378:metabolism* / Q000473:pathology / Q000601:surgery; D008099:Liver / Q000378:metabolism; D008264:Macrophages / Q000378:metabolism; D008297:Male; D051379:Mice; D011956:Receptors, Cell Surface / Q000378:metabolism
D001057:Apolipoproteins E; D017077:Culture Media, Conditioned; D011956:Receptors, Cell Surface; D002784:Cholesterol