Much has recently been learned about the processes involved in postprandial
triacylglycerol clearance. As discussed previously, important differences in the metabolism of
chylomicrons and VLDL have become apparent. The ASP pathway has also been recognized and appears to play a critical role in
chylomicron metabolism. The ASP pathway is activated in order to trap the
fatty acids released from
chylomicrons by the action of LPL and there is now unequivocal in vivo evidence in human subjects that ASP is generated by adipocytes in the postprandial period. These findings match the in vitro data showing that
chylomicrons, but not the other plasma
lipoproteins or
fatty acids, activate the generation of ASP by cultured human adipocytes. An inverse relationship appears to exist between the proportion of
fatty acids taken up by adipocytes and that released into the general circulation. Too great a release into the general circulation because of diminished trapping of
fatty acids released from
chylomicrons appears to be critical in the pathogenesis of the dyslipoproteinaemias associated with hyperapo B or FCHL and omental
obesity. Evidence has been presented that dysfunction of the ASP pathway may be one of the causes of this disorder. Put differently, the ASP pathway is essential for the normal clearance and disposition of dietary
fatty acids. Binding of
chylomicrons to capillary endothelium followed by lipolysis by LPL results in the sudden liberation of
fatty acids, and in the marked generation of ASP by adipocytes. The ASP that is generated is essential if LPL is to continue to form
fatty acids at a normal rate. It is essential also if the
fatty acids which are formed are to enter the adipocyte rather than exit into the general circulation. The transport vehicle, the
chylomicron, therefore stimulates the formation of the
peptide, ASP, which is responsible for its successful metabolism. Thus, the ASP pathway provides the metabolic coordination between the
chylomicron and the adipocyte, which we describe as microenvironmental metabolic regulation and which we believe is essential for the normal clearance of dietary
triacylglycerol from plasma.