Effects of dexamethasone and insulin on the synthesis of triacylglycerols and phosphatidylcholine and the secretion of very-low-density lipoproteins and lysophosphatidylcholine by monolayer cultures of rat hepatocytes

Abstract

Rat hepatocytes in monolayer culture were preincubated for 19 h with 1 microM-dexamethasone, and the incubation was continued for a further 23 h with [14C]oleate, [3H]glycerol and 1 microM-dexamethasone. Dexamethasone increased the secretion of triacylglycerol into the medium in particles that had the properties of very-low-density lipoproteins. The increased secretion was matched by a decrease in the triacylglycerol and phosphatidylcholine that remained in the hepatocytes. Preincubating the hepatocytes for the total 42 h period with 36 nM-insulin decreased the amount of triacylglycerol in the medium and in the cells after the final incubation for 23 h with radioactive substrates. However, insulin had no significant effect on the triacylglycerol content of the cell and medium when it was present only in the final 23 h incubation. Insulin antagonized the effects of dexamethasone in stimulating the secretion of triacylglycerol from the hepatocytes, especially when it was present throughout the total 42 h period. The labelling of lysophosphatidylcholine in the medium when hepatocytes were incubated with [14C]oleate and [3H]glycerol was greater than that of phosphatidylcholine. The appearance of this lipid in the medium, unlike that of triacylglycerol and phosphatidylcholine, was not stimulated by dexamethasone, or inhibited by colchicine. However, the presence of lysophosphatidylcholine in the medium was decreased when the hepatocytes were incubated with both dexamethasone and insulin. These findings are discussed in relation to the control of the synthesis of glycerolipids and the secretion of very-low-density lipoproteins and lysophosphatidylcholine by the liver, particularly in relation to the interactions of glucocorticoids and insulin.

Fatty acid uptake and metabolism to ketone bodies and triacylglycerol in rat and human hepatocyte cultures is dependent on chain‐length and degree of saturation Effects of carnitine and glucagon

“…To date, the majority of studies on fatty acid metabolism in rat hepatocyte cultures have been performed in the absence of exogenous carnitine, under conditions where P-oxidation is very low [9,15]. This study shows that in the absence of exogenous carnitine the net rates of intracellular triacylglycerol deposition are significantly higher than in the presence of carnitine and the patterns of triacylglycerol deposition for the various substrates were also different.…”

“…In order to investigate the validity of tion in hepatocyte cultures have been conducted in the absence of carnitine supplementation. Conseextrapolating from rat hepatocytes to the human quently, partitioning of fatty acids towards ,& oxidation is very low [9,15]. Differing degrees of carnitine deficiency might explain some of the anomalies in the literature on the effects of fatty acid chain length and unsaturation on glycerolipid formation [3, 6,8,10].…”

Glucagon, cyclic AMP and adrenaline stimulate the degradation of low-density lipoprotein by cultured rat hepatocytes

“…However, a parallel situation may also exist in the control of VLDL secretion. Thus insulin [34][35][36][37][38][39][40], glucagon [40,41] and adrenaline [42] have been reported to decrease this process. Conversely dexamethasone stimulates VLDL secretion and insulin counteracts its effects [39,43].…”

“…Thus insulin [34][35][36][37][38][39][40], glucagon [40,41] and adrenaline [42] have been reported to decrease this process. Conversely dexamethasone stimulates VLDL secretion and insulin counteracts its effects [39,43]. It therefore appears that the hypertriglyceridaemia and hypercholesterolaemia that are often associated with uncontrolled diabetes could be partly caused by the increased action of glucocorticoids relative to insulin [11].…”

Comparison of albumin-mediated release of lysophosphatidylcholine and lysophosphatidylethanolamine from cultured rat hepatocytes

“…It has been shown that albumin stimulates the release of lysophosphatidylcholine from isolated perfused rat liver (Sekas et al, 1985) and cultured rat hepatocytes (Mangiapane & Brindley, 1986;Graham et al, 1988a,b;Baisted et al, 1988;Robinson et al, 1989). The released lysophosphatidylcholine appears to be formed by the action of phospholipases A1 and A2 on cellular phosphatidylcholine and not by the degradation of secreted lipoprotein phosphatidylcholine.…”