Increase of fatty acid oxidation and VLDL assembly and secretion overexpression of PTEN in cultured hepatocytes of newborn calf

Abstract

Background: Phosphatase and tensin homolog (PTEN) is a potent tumor suppressor gene that also plays a vital role in regulating fatty acid metabolism. Here we attempted to elucidate the role of PTEN in the regulation of fatty acid oxidation and the assembly and secretion of very low density lipoprotein (VLDL) in dairy cow liver.

Methods: We transfected primary culture calf hepatocytes with adenovirus-mediated PTEN overexpression vector (AD-GFP-PTEN).PTEN-overexpressing hepatocytes and control hepatocytes were obtained.

Results: Compared with controls, overexpression of PTEN significantly up-regulated CPT I, ACSL, HADH expression (p<0.05), which are all involved in fatty acid oxidation. At the same time, the expression of ApoB100 (p<0.01), ApoE (p<0.05) and MTP (p<0.01) increased. Therefore, the assembly and secretion of VLDL was enhanced (p<0.05). The expression of LDLR was slightly up-regulated, but there was no significant difference (p>0.05). To demonstrate that fatty acid metabolism was changed, we measured the concentrations of TG and VLDL. The concentration of TG was significantly decreased in hepatocytes (p<0.01), while the concentration of VLDL was significantly increased in the medium (P<0.05).

Conclusions: Overexpressing PTEN enhanced fatty acid oxidation and assembly and secretion of VLDL. PTEN gene therapy could have therapeutic potential for fatty liver diseases of dairy cattle.