Time-dependent effects of insulin on lipid synthesis in cultured fetal rat hepatocytes: A comparison between lipogenesis and glycogenesis

The lipogenic effect of insulin was studied in 18-day-old fetal rat hepatocytes after 2 to 3 days of culture in the presence of glucocorticoids when an acute stimulatory effect of insulin on glycogenesis was present. The rate of [1- 14C]-acetate incorporation into lipids measured for 4 hours was muc...

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Bibliographic Details
Published in:Metabolism, clinical and experimental clinical and experimental, 1997-04, Vol.46 (4), p.345-354
Main Authors: M'Zali, H., Guichard, C., Lavau, M., Plas, C.
Format: Article
Language:English
Subjects:
Acetates - metabolism
Animals
Biological and medical sciences
Carbon Radioisotopes
Cells, Cultured
Endocrine pancreas
Enzyme Activation
Fatty Acid Synthases - metabolism
Fluorescence
Fundamental and applied biological sciences. Psychology
Glucose - metabolism
Hormones. Régulation
Insulin - pharmacology
Lipids - biosynthesis
Liver - cytology
Liver - drug effects
Liver - embryology
Liver - metabolism
Liver Glycogen - biosynthesis
Malate Dehydrogenase - metabolism
Rats
Rats, Sprague-Dawley
Vertebrates: endocrinology
Citations: Items that this one cites
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Summary:The lipogenic effect of insulin was studied in 18-day-old fetal rat hepatocytes after 2 to 3 days of culture in the presence of glucocorticoids when an acute stimulatory effect of insulin on glycogenesis was present. The rate of [1- 14C]-acetate incorporation into lipids measured for 4 hours was much higher than with [U- 14C]-glucose (30 v 3.8 nmol/h/mg protein). The stimulatory effect of insulin on lipid labeling remained weak (1.2-fold) and contrasted with its striking stimulatory effect on [U- 14C]-glucose incorporation into glycogen (fourfold). When lipid labeling was assessed in longer experiments, increasing acetate concentrations in the medium stimulated the incorporation rate of [1- 14C]-acetate into lipids (3.5-fold from 1 to 5 mmol/L after 36 hours) and decreased that of [U- 14C]-glucose (by twofold). The stimulatory effect of insulin on the rate of lipid labeling developed with both precursors from 12 to 36 hours after insulin exposure (by ∼twofold) independently of acetate concentration and was not glucocorticoid-dependent, contrary to the glycogenic response. Addition of a glucose load simultaneously with insulin increased the stimulation of lipogenesis when measured with [U- 14C]-glucose (twofold to 3.7-fold). Besides contributing to an accumulation of larger and numerous lipid droplets in the cells, insulin increased fatty acid synthase activity by 26%, whereas malic enzyme was not affected. Thus, insulin-dependent lipogenesis in cultured fetal hepatocytes appears to be mostly regulated by a long-term mechanism, contrary to the glycogenic effect of insulin.
ISSN:0026-0495
1532-8600
DOI:10.1016/S0026-0495(97)90045-7