Postnatal development of hepatocellular apolipoprotein B assembly and secretion in the rat

Dietmar Plonné,Hans-Peter Schulze,Ulla Kahlert,Kerstin Meltke,Holger Seidolt,Andrew J Bennett,Ian J Cartwright,Joan A Higgins,Uwe Till,Rolf Dargel

doi:10.1016/s0022-2275(20)31513-3

Dietmar Plonné, Hans-Peter Schulze + Show 8 more

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https://doi.org/10.1016/s0022-2275(20)31513-3

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Abstract

In this study, we explored the paradox that in suckling rats the serum concentration of LDL is high although the liver secretes only minimal quantities of VLDL, the presumed precursor of LDL. Freshly isolated hepatocytes and hepatocytes in primary culture obtained from adult (90 days old) and suckling (17 days old) rats were used to investigate the synthesis and secretion of apolipoprotein B (apoB) and lipids as well as the density profile of secreted apoB-containing lipoproteins. Furthermore, the effects of dexamethasone and oleate on apoB biogenesis were investigated in primary cultures of hepatocytes from adult and suckling rats. Hepatocytes from suckling rats were unable to assemble mature VLDL but secreted apoB as primordial lipoprotein particles in the LDL-HDL density range. Intracellular degradation of apoB was also reduced in hepatocytes from suckling rats compared with that in hepatocytes from adults. The immaturity in VLDL assembly and apoB degradation of hepatocytes from suckling rats could be overcome by treating the cultures with dexamethasone plus oleate or dexamethasone alone. The lower microsomal triacylglycerol transfer protein (MTP) mRNA concentrations in hepatocytes from suckling rats in comparison with hepatocytes from adult rats were not reflected in lower MTP activity levels. Furthermore, dexamethasone plus oleate treatment had no effect on MTP activity although VLDL assembly and secretion were clearly stimulated. We conclude that, during the suckling period of the rat, serum LDL is directly produced by the liver. This is a result of impaired hepatic VLDL assembly, which is a consequence of low triglyceride synthesis and an inefficient mobilization of bulk lipids in the second step of VLDL assembly.—Plonné, D., H-P. Schulze, U. Kahlert, K. Meltke, H. Seidolt, A. J. Bennett, I. J. Cartwright, J. A. Higgins, U. Till, and R. Dargel. Postnatal development of hepatocellular apolipoprotein B assembly and secretion in the rat.

Highlights

In this study, we explored the paradox that in suckling rats the serum concentration of LDL is high the liver secretes only minimal quantities of VLDL, the presumed precursor of LDL
The results presented in this study provide evidence that hepatocytes from suckling rats do not assemble mature VLDL but secrete apolipoprotein B (apoB) as lipoprotein particles in the LDL-HDL density range
The density profiles of apoB-containing lipoproteins secreted by freshly isolated hepatocytes were similar to those of apoB-containing lipoproteins secreted by cells in primary culture (Fig. 4)

Summary

Introduction

We explored the paradox that in suckling rats the serum concentration of LDL is high the liver secretes only minimal quantities of VLDL, the presumed precursor of LDL. Isolated hepatocytes and hepatocytes in primary culture obtained from adult (90 days old) and suckling (17 days old) rats were used to investigate the synthesis and secretion of apolipoprotein B (apoB) and lipids as well as the density profile of secreted apoB-containing lipoproteins. During the suckling period the high fat, low carbohydrate This hypothesis is supported by the fact that the visceral yolk sac of the rat [23,24,25,26] and Hep-G2 cells [27, 28], both of which have low triglyceride synthesis or availability, secrete apoB as lipoprotein particles in the LDL but not in the VLDL density range. Our experiments demonstrated that without additives hepatocytes from suckling rats do not produce VLDL particles but secrete apoB in the LDL-HDL density range because of immature apoB assembly. After addition of both oleic acid and dexamethasone to the culture medium do hepatocytes from suckling animals secrete apoB in the VLDL density range, similar to hepatocytes prepared from adult rats

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