Abstract

In order to explore the role of forkhead box protein O1 (FoxO1) in the lipid metabolism and cell proliferation, goose primary hepatocytes were isolated and incubated with insulin or PI3K-Akt-mTOR pathway dual inhibitor NVP-BEZ235, and then transfected with FoxO1 interference plasmid. The related parameters of lipid metabolism and cell proliferation were measured. The results firstly showed that FoxO1 interference increased the intracellular TG and lipids concentration (P < 0.05); and increased the proliferative index (PI), cell DNA synthesis, protein expression of Cyclin D1 in goose primary hepatocytes (P < 0.05). Secondly, the co-treatment of insulin and FoxO1 interference increased the mRNA level and protein content of Cyclin D1 (P < 0.05); however, there was no significant difference between the insulin treatment and the co-treatment of insulin and miR-FoxO1 interference in the intracellular TG and lipids concentration and PI (P > 0.05). Lastly, the decrease of intracellular TG and lipids concentration and PI induced by NVP-BEZ235 was up-regulated by FoxO1 interference significantly (P < 0.05). In summary, FoxO1 could regulate the lipids metabolism and cell proliferation mediated by PI3K-Akt-mTOR signaling pathway in goose primary hepatocytes. Further investigations are required to highlight the potential role of FoxO1 in the lipid metabolism and cell proliferation mediated by insulin in goose primary hepatocyte.

Highlights

  • The transcription factor forkhead box protein O1 (FoxO1) is a member of the forkhead O family and plays important roles in different biological processes which includ cell proliferation and cell lipid metabolism

  • Our current research reported that the regulation of lipid deposition by insulin in goose liver cells was mediated by the phosphatidylinositide 3-kinases (PI3K)-protein kinase B (Akt)-Mammalian target of rapamycin (mTOR) signaling pathway (Han et al, 2015)

  • acylCoA oxidase 1 (ACOX1), which indicated that fatty acid oxidation decreased after FoxO1 interference, which is in line with a previous study that FoxO1 proteins exerted important effects on fatty acid oxidation via the regulation of adipose triacylglycerol lipase reported by Zhang et al (2016)

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Summary

Introduction

The transcription factor forkhead box protein O1 (FoxO1) is a member of the forkhead O family and plays important roles in different biological processes which includ cell proliferation and cell lipid metabolism. Previous researches showed that FoxO1 regulates hepatic lipid metabolism in multiple ways, including PP2A-AMPK pathway, insulin pathway, glucose pathway, AKT-FoxO1 pathway (Chen et al, 2020; Shi et al, 2020; Yu et al, 2019; Zangerolamo et al, 2019), from the de novo lipogenesis via sterol regulatory element-binding proteins-1 (SREBP-1), fatty acids oxidation and lipids transportation. The insulin signaling through FoxO1 plays an important role in regulating hepatic microsomal triglyceride transfer protein (MTP) expression and very low-density lipoprotein (VLDL) production (Zangerolamo et al, 2019). Our current research reported that the regulation of lipid deposition by insulin in goose liver cells was mediated by the PI3K-Akt-mTOR signaling pathway (Han et al, 2015).

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