Hepatic lipoprotein biosynthesis

123

1. The precise effects of insulin, dexamethasone and lipogenic precursors on the secretion of very-low-density lipoprotein (VLDL) cholesterol and triacylglycerol were dependent on the age of the culture and the duration of treatment. 2. The rates of secretion of triacylglycerol and cholesterol gradually declined with the age of the culture, although there was no detectable decrease within a given 24 h period. 3. Between 4 h and 24 h after cell preparation, insulin inhibited VLDL secretion. Inhibition was maximal between 6 and 12 h after addition of insulin. Longer-term treatment (24-48 h) with insulin resulted in a stimulation of VLDL secretion. This effect was less apparent when dexamethasone was simultaneously present. The secretion of triacylglycerol and cholesteryl ester was more sensitive to insulin than was that of non-esterified cholesterol. 4. Dexamethasone alone stimulated the secretion of VLDL to an extent which increased with the age of the culture. In young cultures (up to 24 h old) dexamethasone protected against inhibition by insulin, but was ineffective in older cultures. 5. In young cultures the stimulatory effect of lipogenic precursors (lactate and pyruvate) on the secretion of triacylglycerol and cholesterol was more pronounced in the presence of dexamethasone. In cultures older than 24 h, the secretion of these components was less sensitive to short-term stimulation by lactate and pyruvate.

Section: Discussioncontrasting

confidence: 54%

Short- and longer-term regulation of very-low-density lipoprotein secretion by insulin, dexamethasone and lipogenic substrates in cultured hepatocytes. A biphasic effect of insulin

Bartlett

Gibbons

1988

123

“…These results suggested that apoprotein E may not be required for the hepatic recognition of remnants. Since in the isolated perfused liver lipoproteins and, presumably, also free apoprotein E are continuously secreted by the hepatocytes into the perfusion medium (Marsh, 1986), the possibility could not be ruled out that the proteinase-treated remnants re-acquired apoprotein E before being taken up by the hepatocytes. However, for this explanation to be valid, it is necessary to postulate either that the proteinase-treated chylomicrons, which were poorly taken up by the liver, did not acquire apoprotein E, or that they acquired lesser amounts of this apoprotein than the proteinase-treated remnants.…”

Section: Resultsmentioning

confidence: 99%

Apoprotein-independent binding of chylomicron remnants to rat liver membranes

Borensztajn

Kotlar

Chang

1991

Rat lymph chylomicrons and chylomicron remnants were treated with trypsin or Pronase. The ability of the resulting apoprotein-free lipoproteins to be taken up by the isolated perfused rat liver, and to bind to isolated rat liver membranes, was examined. Compared with control lipoproteins, the apoprotein-free chylomicrons and remnants retained unaltered their capacity to be differentiated by the intact liver and by the isolated membranes. Further, control remnants and apoprotein-free remnants competed for binding to the isolated membranes. We conclude that apoproteins are not required for the hepatic differentiation between chylomicrons and remnants, and suggest that the lipoprotein phospholipids may play a direct role in this process.

“…Insulin-dependent diabetes is almost invariably associated with an increased concentration of plasma nonesterified fatty acids [4]. Exogenous fatty acids are wellestablished precursors of hepatic VLDL [39][40][41][42][43][44], and it may be argued that the decreased VLDL triacylglycerol output in the diabetic hepatocytes compared with normal was a result of extracellular fatty acid deficiency rather than of diabetes itself. To investigate this possibility, hepatocyte cultures from normal and from diabetic animals were incubated with or without 0.75 mM-oleate for 24 h (Protocol A; 4-24 h after plating).…”

Section: Effects Of Insulin On Vldl Lipid Secretionmentioning

confidence: 99%

Regulation of very-low-density-lipoprotein lipid secretion in hepatocyte cultures derived from diabetic animals

Duerden

Bartlett

Gibbons

1989

Hepatocytes were derived from 2-3-day streptozotocin-diabetic rats and maintained in culture for up to 3 days. Compared with similar cultures from normal animals, these hepatocytes secreted less very-low-density-lipoprotein (VLDL) triacylglycerol, but the decrease in the secretion of VLDL non-esterified and esterified cholesterol was not so pronounced. This resulted in the secretion of relatively cholesterol-rich VLDL particles by the diabetic hepatocytes. Addition of insulin for a relatively short period (24 h) further decreased the low rates of VLDL triacylglycerol secretion from the diabetic hepatocytes. The secretion of VLDL esterified and non-esterified cholesterol also declined. These changes occurred irrespective of whether or not exogenous fatty acids were present in the culture medium. Little or no inhibitory effect of insulin was observed after longer-term (24-48 h) exposure to the hormone. Both dexamethasone and a mixture of lipogenic precursors (lactate plus pyruvate) stimulated VLDL triacylglycerol and cholesterol secretion, but not to the levels observed in hepatocytes from normal animals. The low rate of hepatic VLDL secretion in diabetes contrasts with the increase in whole-body VLDL production rate. This suggests that the intestine is a major source of plasma VLDL in insulin-deficient diabetes.