ANGPTL4 supports glutamine metabolism and promotes fatty acid oxidation in nonsmall cell lung cancer cells

Background Angiopoietin-like proteins (ANGPTLs) 4 is key factor in the regulation of lipid and glucose metabolism in metabolic diseases. It also has been demonstrated highly expressed in cancers, but the regulation of energy metabolism on tumor remains to be determined.Methods Two different NSCLC cells A549 and H1299 were used to investigate the role of ANGPTLs 4 in energy metabolism by tracer technique and seahorse XF technology in ANGPTLs4 knockdown cell. RNA microarray and specific inhibitors were used in identification targets in overexpression ANGPTLs4 cells.Results Knockdown ANGPTLs4 could inhibit the energy metabolism and proliferation of NSCLC cells. Knockdown ANGPTLs4 had no significant effect on glycolysis, but affected the glutamine consumption and fatty acid oxidation. Knockdown ANGPTLs4 also significantly inhibited the growth of metastasis and energy metabolism of tumor in mice, but had a weak effect on glycolysis. RNA microarray analysis showed that ANGPTLs4 significantly affected GLS and CPT1. ANGPTLs4 overexpression cells exposed to glutamine deprivation, the effect on cell proliferation and energy metabolism were significantly decreased, but still has difference compared with normal NSCLC cells. ANGPTLs4 overexpression cells treated with GLS and CPT1 inhibitor at the same time, the regulatory effects on cell proliferation and energy metabolism were disappeared.Conclusions ANGPTLs4 could promote the glutamine consumption and fatty acid oxidation, but not glycolysis, and accelerated the energy metabolism in NSCLC.