Rader D

References (2)

Title : Potential role of hepatic lipase in the accretion of docosahexaenoic acid (DHA) by the brain - Sugasini_2021_Biochim.Biophys.Acta.Mol.Cell.Biol.Lipids__159002
Author(s) : Sugasini D , Yang P , Ng D , Khetarpal S , Vitali C , Rader D , Subbaiah PV
Ref : Biochimica & Biophysica Acta Molecular & Cellular Biology Lipids , :159002 , 2021
Abstract : DHA (docosahexaenoic acid) is an essential fatty acid that is required for the normal development and function of the brain. Because of its inability to synthesize adequate amounts of DHA from the precursors, the brain has to acquire DHA from plasma through the blood brain barrier (BBB). Recent studies demonstrated the presence of a transporter at the BBB that specifically transports DHA into the brain in the form of lysophosphatidylcholine (LPC-DHA). However, the mechanism by which LPC-DHA is generated in the plasma is not known. Our previous studies showed that there are at least three different enzymes - lecithin cholesterol acyltransferase (LCAT), endothelial lipase (EL), and hepatic lipase (HL), which can generate LPC-DHA from sn-2 DHA phosphatidylcholine. Here we determined the relative contributions of these enzymes in the delivery of DHA to the brain by measuring the brain DHA levels in the mice deficient in each of these enzymes. The results show that the brain DHA levels of LCAT-deficient mice or EL-deficient mice were not significantly lower than those of their littermates. However, brain DHA was significantly decreased in HL deficient mice (13.5% of total fatty acids) compared to their littermates (17.1%) (p<0.002), and further decreased to 8.3% of total fatty acids in mice deficient in both HL and EL. These results suggest that HL activity may be the major source for the generation of LPC-DHA in the plasma necessary for transport into the brain, and EL might contribute to this process in the absence of HL.
ESTHER : Sugasini_2021_Biochim.Biophys.Acta.Mol.Cell.Biol.Lipids__159002
PubMedSearch : Sugasini_2021_Biochim.Biophys.Acta.Mol.Cell.Biol.Lipids__159002
PubMedID: 34197964

Title : S447X variant of the lipoprotein lipase gene, lipids, and risk of coronary heart disease in 3 prospective cohort studies - Jensen_2009_Am.Heart.J_157_384
Author(s) : Jensen MK , Rimm EB , Rader D , Schmidt EB , Sorensen TI , Vogel U , Overvad K , Mukamal KJ
Ref : American Heart Journal , 157 :384 , 2009
Abstract : BACKGROUND: Lipoprotein lipase (LPL) has a prominent role in the metabolism of triglycerides (TGs) and high-density lipoprotein cholesterol (HDL-C) and is a potential interesting target for the development of antiatherogenic treatment. To provide deeper insight into the role of natural variation in this gene, we investigated the association between the LPL S447X variant with lipids and risk of coronary heart disease (CHD) in 3 independent, prospective studies. METHODS: The S447X variant was genotyped in case-control studies of incident CHD nested within the Nurses' Health Study (NHS), the Health Professionals Follow-up Study (HPFS), and the Danish Diet, Cancer and Health (DCH) study, totaling 245, 258, and 962 cases, respectively. RESULTS: S447X carriers tended to have lower TG and higher HDL-C concentrations than noncarriers. The S447X variant was associated with a lower risk of CHD in the NHS; the association was weaker in the HPFS and not statistically significant in the DCH women and men. The pooled relative risk per minor allele was 0.74 (0.56-1.00). There was a suggestion that the associations of the S447X variant with plasma lipids and CHD risk were more pronounced in obese individuals in the NHS study, but this finding was not consistent across the studies. CONCLUSIONS: The LPL S447X variant tended to be associated with lower TG and higher HDL-C levels, and lower risk of CHD in all 3 cohorts. Lipoprotein lipase is an attractive target for clinical intervention, but studies are needed to clarify whether greater benefit from this variant may be conferred in some subgroups.
ESTHER : Jensen_2009_Am.Heart.J_157_384
PubMedSearch : Jensen_2009_Am.Heart.J_157_384
PubMedID: 19185650