Role of high density lipoproteins in regulation of hepatic fatty acid synthesis by chylomicron and very low density lipoprotein remnants.

Abstract

High density lipoproteins (HDL) have been implicated in the transformation of native triglyceride-rich lipoproteins into their corresponding remnant particles during the action of peripheral lipoprotein lipase. The subsequent metabolism of these remnant particles by the liver results in the inhibition of hepatic lipogenesis. In the present study, remnant particles of chylomicrons or very low density lipoproteins (VLDL) have been generated in the perfused heart system both in the absence and presence of HDL. These have been characterized chemically, and the effects of both native lipoproteins and their respective remnants on fatty acid synthetic rates of hepatocytes have been assessed. Thirty to sixty-six per cent of the triglyceride moieties of native lymph chylomicrons or VLDL were hydrolyzed during a 45-min heart perfusion whether or not HDL was present in the perfusion media. Chylomicron remnants produced in the absence of HDL (25-300 micrograms/ml) caused only 10-20% inhibition of hepatic fatty acid synthesis, whereas remnants produced in the presence of HDL caused up to 78% inhibition at equivalent protein concentrations. The nonsuppressive remnants (produced in the absence of HDL) were converted to suppressive remnants upon incubation with HDL. Similar results were obtained with VLDL remnants produced in the absence and presence of HDL. The sodium dodecyl sulfate-polyacrylamide gel electrophoresis apoprotein profiles of the nonsuppressive and suppressive remnants indicated a marked loss of the C apoproteins during the conversion of native chylomicrons or the nonsuppressive remnants to the suppressive remnants. Thus, HDL seems to be required for the removal of apoprotein C during the transformation of triglyceride-rich lipoproteins to the suppressive remnants. There was, however, no enrichment of apo-E on the suppressive remnant particles. We, thus, could not verify the suggested role of HDL in enriching the suppressive remnants with apoproteins E.