Increased lipolysis by secretory phospholipase A(2) group V of lipoproteins in diabetic dyslipidaemia.
BACKGROUND
Lipolysis of lipoproteins by secretory phospholipase A(2) group V (sPLA(2)-V) promotes inflammation, lipoprotein aggregation and foam cell formation--all considered as atherogenic mechanisms.


OBJECTIVE
In this study, we compared the susceptibility to sPLA(2)-V lipolysis of VLDL and LDL from individuals with type 2 diabetes and the metabolic syndrome (T2D-MetS) and from healthy controls. Design. VLDL and LDL were isolated from 38 T2D-MetS subjects and 38 controls, treated pair-wise. Extent of sPLA(2)-V lipolysis was measured as release of nonesterified free fatty acids (NEFA). In a subset of the subjects, lipoprotein composition was determined as a relationship between lipid and apolipoprotein components.


RESULTS
Mean paired increase in sPLA(2)-V lipolysis after 1 h for T2D-MetS versus control was 2.0 micromol NEFA l(-1) for VLDL (P = 0.004) and 0.75 micromol NEFA l(-1) for LDL (P = 0.001). There were also substantial differences in lipoprotein composition between the groups. T2D-MetS VLDL had higher triglyceride and cholesterol contents than control VLDL. T2D-MetS LDL was smaller and contained more triglycerides and less cholesterol than control LDL. Both VLDL and LDL from T2D-MetS subjects also contained more apolipoprotein CIII per particle.


CONCLUSIONS
VLDL and LDL from T2D-MetS individuals were more susceptible to sPLA(2)-V lipolysis than those from control individuals. This may result in elevated levels of NEFA and lysophosphatidylcholine, both in circulation and in LDL, possibly contributing to the elevated inflammatory state and increased risk of cardiovascular diseases seen in these individuals.
Pettersson
C
C
Department of Molecular and Clinical Medicine, The Wallenberg Laboratory, Sahlgrenska Academy University of Gothenburg, Gothenburg, Sweden. camilla.pettersson@wlab.gu.se
Fogelstrand
L
L
Rosengren
B
B
Ståhlman
S
S
Hurt-Camejo
E
E
Fagerberg
B
B
Wiklund
O
O
D000704:Analysis of Variance; D002784:Cholesterol / Q000097:blood; D003324:Coronary Artery Disease / Q000201:enzymology; D003924:Diabetes Mellitus, Type 2 / Q000201:enzymology / Q000378:metabolism*; D050171:Dyslipidemias / Q000201:enzymology / Q000378:metabolism*; D004797:Enzyme-Linked Immunosorbent Assay; D005230:Fatty Acids, Nonesterified / Q000097:blood; D005260:Female; D054505:Group V Phospholipases A2 / Q000378:metabolism*; D006801:Humans; D008066:Lipolysis / Q000502:physiology*; D008077:Lipoproteins, LDL / Q000302:isolation & purification / Q000378:metabolism*; D008079:Lipoproteins, VLDL / Q000302:isolation & purification / Q000378:metabolism*; D024821:Metabolic Syndrome / Q000201:enzymology; D008875:Middle Aged; D018709:Statistics, Nonparametric
D005230:Fatty Acids, Nonesterified; D008077:Lipoproteins, LDL; D008079:Lipoproteins, VLDL; D002784:Cholesterol; D054505:Group V Phospholipases A2