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Diabetic Dyslipidemia and Exercise alter the Plasma Low Density Lipoproteome
Author(s) -
Richardson Matthew R,
Dixon Joseph,
Sturek Michael,
Witzmann Frank
Publication year - 2006
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.20.4.a529
Subject(s) - dyslipidemia , glycation , medicine , chemistry , endocrinology , apolipoprotein b , lipidome , diabetes mellitus , biochemistry , cholesterol , lipid metabolism
A role for post‐translationally modified (PTM) low density lipoproteins (LDL) has been proposed in the development of coronary artery disease (CAD), yet little is known about the type or extent of such PTMs. Diabetics are 3‐4 times more likely to develop CAD and undergo enhanced LDL glycation, the latter considered a putative atherosclerotic accelerant. Increased coronary vascular constriction in a swine model of diabetic dyslipidemia (DD) was prevented by exercise training (DDX) without altering total LDL concentration (Mokelke et al. J. Appl. Physiol. 95:1179, 2003). A decrease in the number and/or extent of LDL modifications may explain the cardioprotective effects of exercise. We tested the hypothesis that the low density lipoproteome is altered both in abundance and PTMs in a diabetic state and by exercise. The lipoproteins, isolated by FPLC from normolipidemic controls, DD, and DDX pigs, were analyzed by 2‐D gel electrophoresis and identified by peptide mass fingerprinting. Of 430 spots matched across all gel patterns analyzed, 171 spots were differentially expressed (p ≤ 0.05) and their identities determined. Apolipoprotein E abundance increased in DD, but showed the greatest increase in DDX. To compare the extent of PTMs the charge modification index (CMI) of each LDL charge train was calculated. One such charge train, phospholipase C, increased in overall abundance and CMI in DD and to a lesser extent in DDX, thus supporting our hypothesis. Similar effects in other LDL proteins suggest significant differences in LDL protein modification, the nature of which requires the use of tandem mass spectrometric techniques in a subsequent investigation. Supported by NIH RR13223, HL62552 (MS) and AFOSR 49620‐002‐1‐0089 & FA9550‐05‐1‐0216 (FW).