GDF11 rapidly increases lipid accumulation in liver cancer cells through ALK5-dependent signaling

Hepatocellular carcinoma (HCC) is one of the fastest-growing causes cancer-related mortalities worldwide and this trend mimicked by surge non-alcoholic fatty liver disease (NAFLD). Altered hepatic lipid metabolism promotes HCC development through inflammation activation oncogenes. GDF11 a member TGF-β superfamily recent data have implicated as an anti-aging factor that can alleviate high-fat diet induced obesity, hyperglycemia, insulin resistance NAFLD. However, its role in still not fully delineated. The aim present study was to characterize cells accumulation. To achieve this, we performed imaging, biochemical, lipidomic, transcriptomic analyses primary hepatocytes treated with GDF11-activated signaling pathways. treatment rapidly triggered ALK5-dependent SMAD2/3 nuclear translocation elevated droplets cells, but hepatocytes. In ALK5 inhibition hampered GDF11-mediated attenuated Using ultra-high-performance liquid chromatography/mass spectrometry, detected increased accumulation longer acyl-chain di/tri-acylglycerols glycerophospholipids. Unbiased analysis identified PI3K-AKT among top pathways/cellular processes activated cells. summary, supplementation pro-lipogenic gene expression Integration our “omics” pointed GDF11-induced upregulation de novo lipogenesis ALK5/SMAD2/3/PI3K-AKT Thus, could contribute metabolic reprogramming dysregulation without effects on healthy