The Molecular Mechanism Of Leptin Regulates Fatty Acid Netabolism And Oxidative Phosphorylation In Cancer Cells

Leptin is a class of hormone proteins secreted by adipose tissue.Studies have shown that leptin can promote tumor cell growth.Leptin plays a regulatory role in the energy metabolism of tumor cells,and its molecular mechanism of energy metabolism is unclear.Therefore,it is important for clinical treatment of cancer to study the effect of leptin on the energy metabolism of tumor cells and its regulatory mechanism.In this study,HCT116 cells and MCF-7 cells were used as materials.The effects of leptin on the energy metabolism of metabolites and the oxidative phosphorylation activity of HCT116 cells and MCF-7 cells were studied.The expression of CyclinDl protein was increased and the expression of cyclinBl protein was decreased in the cells of HCT116 and MCF-7 cells after leptin treatment.At the same time,the cell ATP content was significantly increased.CD36 and CPT1A were enhanced at the transcriptional level and translation level and FASN was decreased at the transcription level and translation level.TCA circulating protein of PDH and SDHA were enhanced at the protein level.Glycolytic enzyme of LDH was decreased at protein level.Then,the number of mtDNA copy was increased and the mitochondrial membrane potential was increased.The levels of oxidative phosphorylation-related proteins NDUFB8 and ND1 were increased.The changes of cell metabolism protein and oxidative phosphorylation activity were measured and its results showed that the expression levels of AMPK,p-AMPK,C-myc,PGC-la,PGC-1β,NRF1 and TFAM were enhanced.Leptin and proto-oncogene C-myc were showed high expreesion in colorectal cancer tissues.Fatty acid sythase-related enzymes ACC and FASN were low expression in colorectal cancer tissues.The expression of β-oxidation related enzymes CPT1A and AMPK were increased in colorectal cancer tissues.Down-regulation of C-myc by transgenic technology found that fatty acid catabolism and oxidative oxidative phosphorylation activity were reduced,and fatty acid synthesis and metabolism were enhanced.Transiently overexpressing C-myc found that fatty acid catabolism and oxidative phosphorylation activity were enhanced,and fatty acid synthesis and metabolism were decreased.In summary,leptin plays an important role in the regulation of energy metabolism in tumor cells.It enhances cell fatty acid P-oxidation,inhibits fatty acid synthesis,and thus promotes cell tricarboxylic acid cycle,enhances cell oxidative phosphorylation activity,cell ATP levels,and promotes cell proliferation.It may regulate the fatty acid oxidation and oxidative phosphorylation of tumor cells through the C-myc/PGC-1 pathway.This study is important to understand the relationship between leptin on the proliferation and growth of tumor and the regulation of energy metabolism.It lays the foundation for the study of the proliferation of tumor by regulating and blocks the metabolic pathway of tumor cells.