The self-assembled α-lactalbumin-oleic acid complex inhibits ATP supply from both glycolysis and the TCA cycle in HepG2 cells and HepG2-bearing nude mice.

Energy metabolism has been a predominant target for anti-cancer drug development. The self-assembled anti-tumor α-lactalbumin-oleic acid complex (α-LA-OA) affects the energy metabolism of tumor cells, however, the role of targeting energy metabolism in its anti-tumor mechanism still needs to be clarified. α-LA assembled with OA to form a complex with an average diameter of 144.1 ± 7.241 nm, which is 10-fold larger than α-LA alone. Furthermore, the self-assembled α-LA-OA inhibited the ATP supply from both glycolysis and oxidative phosphorylation in HepG2 cells and HepG2-bearing nude mice. The gene expression of enzymes involved in glycolysis (HK2, aldose, PKM2, LDHB) and oxidative phosphorylation (CS, ACO2, IDH2, SDHA) was inhibited. This inhibitory effect was also evident by increased phosphorylation of AMPKα. α-LA-OA also suppressed the expression of HIF-1α and increased the expression of activated caspase-3. These findings demonstrate that the anti-tumor mechanism of α-LA-OA may be related to its inhibitory effect on the ATP supply, which then activates programmed cell death pathways. This study also indicated that α-LA-OA is a potent anti-tumor agent that targets the energy metabolism of tumor cells.

FGF19 alleviates palmitate-induced atrophy in C2C12 cells by inhibiting mitochondrial overload and insulin resistance.

Fibroblast growth factor 19 (FGF19) acts as a novel factor in the regulation of skeletal muscle mass in animal models by regulating energy expenditure. People with obesity have a lower content of FGF19 and lose muscle mass easily. However, as the main energy metabolism organelles, the involvement of mitochondria in the protective effect of FGF19 is still unknown. In this study, the protective effects of FGF19 on palmitate-induced damages in differentiated mouse myoblast cells (C2C12) were studied, including myotube morphology, mitochondrial function and the regulation of pathways and genes. Excessive palmitate resulted in myotube atrophy and activation of the mitochondria-mediated apoptosis pathway in C2C12 cells. Palmitate also inhibited glucose uptake and induced insulin resistance. FGF19 addition during the differentiation of C2C12 cells, returned the palmitate-induced mitochondrial respiration and apoptosis to the control levels and improved the insulin sensitivity. The palmitate-induced upregulation of genes involved in ß-oxidation (PPARß/δ, PPARγ, UCP-1, MCAD) and the downregulation of genes related to myotube atrophy (PPARα, PGC-1α and PGC-1ß) were also alleviated by FGF19. In summary, FGF19 prevented excessive palmitate-induced dysfunction of C2C12 cells by protecting mitochondrial overload and apoptosis and maintaining normal insulin signaling.