Author
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SHEARER, GREGORY - UCD NEPHROLOGY |
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Newman, John |
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Submitted to: Trade Journal Publication
Publication Type: Peer Reviewed Journal Publication Acceptance Date: 9/22/2008 Publication Date: 12/1/2008 Citation: Shearer, G.C., Newman, J.W. 2008. Lipoprotein lipase releases esterified oxylipins from very low-density lipoproteins. Prostaglandins Leukot. Essent. Fatty Acids. 79:215-222. Interpretive Summary: Obesity-associated changes in lipoprotein metabolism and trafficking may be related to elevated levels of cardio vascular risk associated with this condition. We have previously reported that defects in lipoprotein metabolism alter the lipoprotein distribution of oxidized PUFAs, and we speculate that lipoprotein lipase (LpL) is a determinant in the release of VLDL-associated oxylipins. Using an obese rat model, the Zucker rat, we tested this hypothesis. Using 12 wk old normolipidemic (lean) and hyperlipidemic (obese) Zucker-rats, we measured PUFA alcohols, epoxides, diols, ketones and triols (i.e. oxylipins) in the esterified and unesterified fractions of plasma, VLDL, and in LpL lipolysates of VLDL produced under physiologic conditions. The fraction of plasma oxylipins transported by VLDL varied from ~50% (alcohols) to <10% (ketones and triols). Of these, LpL released VLDL-alcohols, -epoxides and -diols but not –ketones. The profiles of oxylipins from plasma, VLDL and lipolysate were each distinct and altered by obesity. Specifically, the content of mid-chain alcohols in each fraction was elevated in obese animals. Lean VLDL epoxides were dominated by 9(10)-epoxyoctadecamonoenoic acid, while obese VLDL epoxids were dominated by 5(6)-epoxyeicosatrienoic acid. The finding that lipoproteins carry a substantial fraction of plasma oxylipins, that the profile of VLDL-oxylipins is distinct from plasma, that the oxylipins are primarily esterified in lipoproteins, that LpL releases oxylipins from VLDL, and that dysoxylipinemias appears to be concurrent with dyslipidemias suggests an important role for the VLDL-LpL axis in tissue targeting of lipoprotein oxylipins. Technical Abstract: Defects in lipoprotein metabolism alter the lipoprotein distribution of oxidized PUFAs, and we speculate that lipoprotein lipase (LpL) is a determinant in the release of VLDL-associated oxylipins. Here, using 12 wk old normolipidemic (lean) and hyperlipidemic (obese) Zucker-rats, we measured PUFA alcohols, epoxides, diols, ketones and triols (i.e. oxylipins) in the esterified and unesterified fractions of plasma, VLDL, and in LpL lipolysates of VLDL produced under physiologic conditions. The fraction of plasma oxylipins transported by VLDL varied from ~50% (alcohols) to <10% (ketones and triols). Of these, LpL released VLDL-alcohols, -epoxides and -diols but not –ketones. The profiles of oxylipins from plasma, VLDL and lipolysate were each distinct and altered by obesity. Specifically, the content of mid-chain alcohols in each fraction was elevated in obese animals. Lean VLDL epoxides were dominated by 9(10)-epoxyoctadecamonoenoic acid, while obese VLDL epoxids were dominated by 5(6)-epoxyeicosatrienoic acid. The finding that lipoproteins carry a substantial fraction of plasma oxylipins, that the profile of VLDL-oxylipins is distinct from plasma, that the oxylipins are primarily esterified in lipoproteins, that LpL releases oxylipins from VLDL, and that dysoxylipinemias appears to be concurrent with dyslipidemias suggests an important role for the VLDL-LpL axis in tissue targeting of lipoprotein oxylipins. |
