Abstract
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.
Highlights
The synthesis of Apolipoprotein E (apoE) by adipocytes has profound effects on adipose tissue lipid flux and gene expression
Provision of WT adipose tissue to apoE knockout (EKO) recipients produced a circulating apoE level of 0.48 mcg per ml in one experiment (14-week-old recipients) and 0.32 mcg per ml in the other (12-week-old recipients) The plasma apoE levels in both adipose tissue transplantation experiments are above the threshold apoE levels reported to correct hyperlipidemia and suppress atherosclerosis in EKO mice after bone marrow transplantation (BMT) or transgenic expression of apoE in adrenal glands [14,15,16,17]
This contrasts with the activity of macrophage-derived apoE derived from bone marrow transplantation, which is capable of both lowering plasma cholesterol as shown in this study and in previous studies and attenuating atherosclerosis as shown in previous studies [14, 15]
Summary
The synthesis of apoE by adipocytes has profound effects on adipose tissue lipid flux and gene expression. Different from circulating apoE produced by bone marrow transplantation (BMT), 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. After BMT into EKO hosts, plasma cholesterol and macrophage-derived apoE are largely within IDL/LDL- and HDL-sized particles. Most cholesterol and adipocyte apoE remain in VLDL. Fat transplantation provides circulating apoE levels similar to those provided by bone marrow transplantation, but it does not suppress hyperlipidemia or atherosclerosis. ApoE derived from adipose tissue does not suppress atherosclerosis or correct hyperlipidemia in apoE knockout mice.
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