TY - JOUR
T1 - The majority of lipoprotein lipase in plasma is bound to remnant lipoproteins
T2 - A new definition of remnant lipoproteins
AU - Sato, Koichi
AU - Okajima, Fumikazu
AU - Miyashita, Kazuya
AU - Imamura, Shigeyuki
AU - Kobayashi, Junji
AU - Stanhope, Kimber
AU - Havel, Peter J
AU - Machida, Tetsuo
AU - Sumino, Hiroyuki
AU - Murakami, Masami
AU - Schaefer, Ernst
AU - Nakajima, Katsuyuki
PY - 2016/10/1
Y1 - 2016/10/1
N2 - Background Lipoprotein lipase (LPL) is a multifunctional protein and a key enzyme involved in the regulation of lipoprotein metabolism. We determined the lipoproteins to which LPL is bound in the pre-heparin and post-heparin plasma. Methods Tetrahydrolipstatin (THL), a potent inhibitor of serine lipases, was used to block the lipolytic activity of LPL, thereby preventing changes in the plasma lipoproteins due to ex vivo lipolysis. Gel filtration was performed to obtain the LPL elution profiles in plasma and the isolated remnant lipoproteins (RLP). Results When ex vivo lipolytic activity was inhibited by THL in the post-heparin plasma, majority of the LPL was found in the VLDL elution range, specifically in the RLP as inactive dimers. However, in the absence of THL, most of the LPL was found in the HDL elution range as active dimers. Furthermore, majority of the LPL in the pre-heparin plasma was found in the RLP as inactive form, with broadly diffused lipoprotein profiles in the presence and absence of THL. Conclusions It is suggested that during lipolysis in vivo, the endothelial bound LPL dimers generates RLP, forming circulating RLP-LPL complexes in an inactive form that subsequently binds and initiates receptor-mediated catabolism.
AB - Background Lipoprotein lipase (LPL) is a multifunctional protein and a key enzyme involved in the regulation of lipoprotein metabolism. We determined the lipoproteins to which LPL is bound in the pre-heparin and post-heparin plasma. Methods Tetrahydrolipstatin (THL), a potent inhibitor of serine lipases, was used to block the lipolytic activity of LPL, thereby preventing changes in the plasma lipoproteins due to ex vivo lipolysis. Gel filtration was performed to obtain the LPL elution profiles in plasma and the isolated remnant lipoproteins (RLP). Results When ex vivo lipolytic activity was inhibited by THL in the post-heparin plasma, majority of the LPL was found in the VLDL elution range, specifically in the RLP as inactive dimers. However, in the absence of THL, most of the LPL was found in the HDL elution range as active dimers. Furthermore, majority of the LPL in the pre-heparin plasma was found in the RLP as inactive form, with broadly diffused lipoprotein profiles in the presence and absence of THL. Conclusions It is suggested that during lipolysis in vivo, the endothelial bound LPL dimers generates RLP, forming circulating RLP-LPL complexes in an inactive form that subsequently binds and initiates receptor-mediated catabolism.
KW - Chylomicron remnants (CM-R)
KW - Lipoprotein lipase (LPL)
KW - Remnant-like lipoprotein particles-cholesterol (RLP-C)
KW - Tetrahydrolipstatin (THL)
KW - Very low density lipoprotein remnants (VLDL-R)
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U2 - 10.1016/j.cca.2016.06.020
DO - 10.1016/j.cca.2016.06.020
M3 - Article
C2 - 27342999
AN - SCOPUS:84982719978
VL - 461
SP - 114
EP - 125
JO - Clinica Chimica Acta
JF - Clinica Chimica Acta
SN - 0009-8981
ER -