Dexamethasone enhanced by insulin, but not by thyroid hormones stimulates apolipoprotein B mRNA editing in cultured rat hepatocytes depending on the developmental stage

Lorentz, Axel; Plonné, Dietmar; Schulze, H.‐P.; Dargel, R.

doi:10.1016/0014-5793(96)00706-5

Cited by 12 publications

(9 citation statements)

References 34 publications

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“…Therefore, the direct effects of GH on hepatocytes are important for the in vivo effects of GH treatment of hypophysectomized rats on hepatic production of apoB-containing lipoproteins. This finding is in contrast to the effect of thyroid hormones, which were shown to increase apoB mRNA editing in vivo (15) but had no effect in vitro (28). Oleic acid and GH had additive effects on apoB-48-VLDL accumulation in the medium, indicating that the combined action of GH and fatty acids on hepatocytes augments apoB-VLDL secretion.…”

Section: Discussionmentioning

confidence: 67%

“…fed state is severalfold higher, the dose of insulin used (3 nM) is within or near the high physiological range. The finding that dexamethasone had a permissive action on the effect of GH on apoB mRNA editing was not surprising, because higher doses of dexamethasone (100 nM) have been shown to increase the editing of apoB mRNA and to enhance the effect of insulin on this process (28).…”

Section: Discussionmentioning

confidence: 98%

“…VLDL secreted from rat hepatocytes are of two different kinds, i.e., containing either apoB-48 or apoB-100 as structural protein (21,30). The editing of apoB mRNA in the rat liver is developmentally regulated (28,50) and dependent on the nutritional status of the animals (2,21,26). During both development and refeeding of fasted rats, increased triglyceride synthesis and secretion from the liver are associated with increased apoB mRNA editing and apoB-48 secretion (2,11,21,26,28,50).…”

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confidence: 99%

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Direct effects of growth hormone on production and secretion of apolipoprotein B from rat hepatocytes

Lindén

Sjöberg

Asp³

et al. 2000

American Journal of Physiology-Endocrinology and Metabolism

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The aim of this study was to investigate the direct effects of growth hormone (GH) on production and secretion of apolipoprotein B (apoB)-containing lipoproteins from hepatocytes. Bovine GH (5-500 ng/ml) was given for 1 or 3 days to rat hepatocytes cultured on laminin-rich matrigel in serum-free medium. The effects of GH were compared with those of 3 nM insulin and 500 microM oleic acid. GH increased the editing of apoB mRNA, and the proportion of newly synthesized apoB-48 (of total apoB) in the cells and secreted into the medium changed in parallel. GH increased total secretion of apoB-48 (+30%) and apoB-48 in very low density lipoproteins (VLDL) more than twofold. Total apoB-100 secretion decreased 63%, but apoB-100-VLDL secretion was unaffected by GH. Pulse-chase studies indicated that GH increased intracellular early degradation of apoB-100 but not apoB-48. GH had no effect on apoB mRNA or LDL receptor mRNA levels. The triglyceride synthesis, the mass of triglycerides in the cells, and the VLDL fraction of the medium increased after GH incubation. Three days of insulin incubation had effects similar to those of GH. Combined incubation with oleic acid and GH had additive effects on apoB mRNA editing and apoB-48-VLDL secretion. In summary, GH has direct effects on production and secretion of apoB-containing lipoproteins, which may add to the effects of hyperinsulinemia and increased flux of fatty acids to the liver during GH treatment in vivo.

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Section: Discussionmentioning

confidence: 67%

Section: Discussionmentioning

confidence: 98%

mentioning

confidence: 99%

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Direct effects of growth hormone on production and secretion of apolipoprotein B from rat hepatocytes

Lindén

Sjöberg

Asp³

et al. 2000

American Journal of Physiology-Endocrinology and Metabolism

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“…GCs also regulate cholesterol and fatty acid synthesis (38) and HDL processing in hepatocytes (39), which can contribute significantly to lipid accumulation and reduced VLDL secretion. In rat hepatocytes, dexamethasone up-regulates HDL binding sites (39) and dexamethasone (with insulin) regulates apolipoprotein gene expression (40,41). Whilst some studies have shown that GCs alone can increase lipid accumulation in hepatocytes (42,43) others have demonstrated a synergistic relationship with insulin to promote lipid accumulation through increased synthesis and decreased secretion (33,44).…”

Section: Glucocorticoids and Nafld (Liver Tissue)mentioning

confidence: 96%

Glucocorticoids and non-alcoholic fatty liver disease

Woods

Hazlehurst

Tomlinson

2015

The Journal of Steroid Biochemistry and Molecular Biology

146

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Non-alcoholic fatty liver disease (NAFLD) is the hepatic manifestation of the global obesity and metabolic disease epidemic and is rapidly becoming the leading cause of liver cirrhosis and indication for liver transplantation worldwide. The hallmark pathological finding in NAFLD is excess lipid accumulation within hepatocytes, but it is a spectrum of disease ranging from benign hepatic steatosis to steatohepatitis through to fibrosis, cirrhosis and risk of hepatocellular carcinoma. The exact pathophysiology remains unclear with a multi-hit hypothesis generally accepted as being required for inflammation and fibrosis to develop after initial steatosis. Glucocorticoids have been implicated in the pathogenesis of NAFLD across all stages. They have a diverse array of metabolic functions that have the potential to drive NAFLD acting on both liver and adipose tissue. In the fasting state, they are able to mobilize lipid, increasing fatty acid delivery and in the fed state can promote lipid accumulation. Their action is controlled at multiple levels and in this review will outline the evidence base for the role of GCs in the pathogenesis of NAFLD from cell systems, rodent models and clinical studies and describe interventional strategies that have been employed to modulate glucocorticoid action as a potential therapeutic strategy.

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“…In spite of substantially reduced hepatic triglyceride synthesis, livers of sucklings contain large amounts of triglycerides (13) but secrete only minimal quantities of VLDL, so that nearly all triglycerides in plasma are of intestinal origin (14)(15)(16). On the other hand, apart from the decreased hepatic apolipoprotein B-48 (apoB-48) production, because of the lower apoB mRNA editing in the liver of sucklings (17)(18)(19)(20) the synthesis and secretion of apoB-100, the main structural component of VLDL, is the same in hepatocytes from suckling and adult animals (16). The different metabolic situations in suckling and adult rats are also reflected by different serum profiles of apoB-containing lipoproteins.…”

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confidence: 99%

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

Plonné

Schulze

Kahlert

et al. 2001

Journal of Lipid Research

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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.

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Dexamethasone enhanced by insulin, but not by thyroid hormones stimulates apolipoprotein B mRNA editing in cultured rat hepatocytes depending on the developmental stage

Cited by 12 publications

References 34 publications

Direct effects of growth hormone on production and secretion of apolipoprotein B from rat hepatocytes

Direct effects of growth hormone on production and secretion of apolipoprotein B from rat hepatocytes

Glucocorticoids and non-alcoholic fatty liver disease

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

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