The Regulation of Lipid Deposition by Insulin in Goose Liver Cells Is Mediated by the PI3K-AKT-mTOR Signaling Pathway

Abstract

BackgroundWe previously showed that the fatty liver formations observed in overfed geese are accompanied by the activation of the PI3K-Akt-mTOR pathway and an increase in plasma insulin concentrations. Recent studies have suggested a crucial role for the PI3K-Akt-mTOR pathway in regulating lipid metabolism; therefore, we hypothesized that insulin affects goose hepatocellular lipid metabolism through the PI3K-Akt-mTOR signaling pathway.MethodsGoose primary hepatocytes were isolated and treated with serum-free media supplemented with PI3K-Akt-mTOR pathway inhibitors (LY294002, rapamycin, and NVP-BEZ235, respectively) and 50 or 150 nmol/L insulin.ResultsInsulin induced strong effects on lipid accumulation as well as the mRNA and protein levels of genes involved in lipogenesis, fatty acid oxidation, and VLDL-TG assembly and secretion in primary goose hepatocytes. The stimulatory effect of insulin on lipogenesis was significantly decreased by treatment with PI3K-Akt-mTOR inhibitors. These inhibitors also rescued the insulin-induced down-regulation of fatty acid oxidation and VLDL-TG assembly and secretion.ConclusionThese findings suggest that the stimulatory effect of insulin on lipid deposition is mediated by PI3K-Akt-mTOR regulation of lipogenesis, fatty acid oxidation, and VLDL-TG assembly and secretion in goose hepatocytes.

Effect of docosahexaenoic acid plus insulin on atherosclerotic human endothelial cells

“…However, the levels of Pal were less in Pal + Insulin compared to the Pal group. One reason would be that the incubation of cells with Insulin increases the in ux of Pal to the inside of the ECs while simultaneously accelerates lipid biogenesis and metabolism [6]. Consistent with our data, previous experiments demonstrated that Insulin has the potential to activate the function of cellmembrane bond lipoprotein lipase and increase the entrance of Pal [7].…”

Fads1 and 2 are promoted to meet instant need for long-chain polyunsaturated fatty acids in goose fatty liver

“…In this study, goose primary hepatocytes were treated with higher dosages (25 or 50 mM) of glucose due to the following consideration: (1) The acute effect of strong stimulation (high glucose) may better mimic the chronic effect of hyperglycemia on the hepatocytes in goose liver than that of weak stimulation (low glucose as in blood); (2) when insulin resistance occurs in goose fatty liver, glucose transporter may pump a large amount of glucose into the hepatocytes in the liver in addition to the diffusion of glucose, which may lead to intracellular glucose level much higher than blood glucose level; (3) Treatment with high level of glucose was previously reported by some in vitro studies [55]. In regard to treatments with 0.25/0.5 mM fatty acids and 100/200 nM insulin, previous studies were also referenced, including those showing serum-free fatty acids were above 0.5 mM in mammalian animals [56][57][58], as well as those using the same or even higher dosages for in vitro studies with mammalian cells and avian cells [55,59,60]. These in vitro studies indicated that the expression of Fads genes was differentially regulated by these factors.…”

The role of endoplasmic reticulum stress and insulin resistance in the occurrence of goose fatty liver

“…We and others previously demonstrated overfeeding could induce dramatic upregulation of genes for de novo lipogenesis in goose liver [17,18], which is consistent with the notion that the liver is the major site of de novo lipogenesis in avian species. Insulin induces strong effects on lipid accumulation, expression of genes for lipogenesis, fatty acid oxidation, and very low density lipoprotein (VLDL)-triacylglycerol (TG) assembly and secretion in primary goose hepatocytes [19,20], and hyperinsulinemia is closely linked to insulin resistance. These findings suggest that IR also plays an important role in the overfeeding-induced goose fatty liver.…”