Omega-3 Triglycerides Modify Blood Clearance and Tissue Targeting Pathways of Lipid Emulsions

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• 作者：Kemin Qi ; Toru Seo ; Maysoon Al-Haideri ; Tilla S. Worgall ; Tikva Vogel ; Yvon A. Carpentier ; and Richard J. Deckelbaum
• 刊名：Biochemistry
• 出版年：2002
• 出版时间：March 5, 2002
• 年：2002
• 卷：41
• 期：9
• 页码：3119 - 3127
• 全文大小：115K
• 年卷期：v.41,no.9(March 5, 2002)
• ISSN：1520-4995

文摘

Omega-3-rich (n-3) triglycerides (TG) are increasingly recognized as having modulating rolesin many physiological and pathological conditions. We questioned whether the catabolism of lipid emulsionswould be changed after enrichment with fish oil (n-3) TG as compared to enrichment with omega-6-richsoy oil (n-6) TG. Phospholipid-stabilized emulsions of n-3 TG and n-6 TG were labeled with [³H]cholesteryloleoyl ether and administered by bolus injection to wild-type (WT) mice, mice lacking the low-densitylipoprotein receptor (LDL-R) (LDL-R -/-), and apolipoprotein E (apoE) knockout mice (apoE -/-).The effects of exogenous apoE, heparin, Triton WR 1339, and lactoferrin on catabolism of emulsionswere also assayed. n-3 TG emulsions were cleared faster from blood and had different extrahepatic tissuetargeting compared to n-6 TG emulsions. In apoE -/- and LDL-R -/- mice, blood clearance of n-6 TGemulsions slowed with decreased liver uptake, but no changes were observed in n-3 TG emulsion clearanceand tissue uptake compared to WT mice. In WT mice, addition of exogenous apoE to the emulsion increasedliver uptake of n-6 TG emulsions but had no impact on n-3 TG emulsions. Pre-injection of heparin increasedand Triton WR 1339 and lactoferrin decreased blood clearance of n-6 TG emulsions with little or noeffect on n-3 TG emulsions. Liver uptake of n-6 TG emulsions increased after heparin injection anddecreased after Triton WR 1339 injection, but uptake of n-3 TG emulsions was not changed. These datashow that the catabolism of n-3 TG emulsions and the catabolism of n-6 TG emulsions occur via verydifferent mechanisms. Removal of chylomicron-sized n-6 TG emulsions is modulated by lipoprotein lipase(LPL), apoE, LDL-R, and lactoferrin-sensitive pathways. In contrast, clearance of chylomicron-sized n-3TG emulsions relies on LPL to a very minor extent and is independent of apoE, LDL-R, and lactoferrin-sensitive pathways.