Adipocyte lipid metabolism regulation by dexamethasone

Abstract

Tumor Microenvironment (TM) has altered its metabolism in a way that favors tumor progression. TM metabolic differences can be found even between different breast cancer (BC) subtypes. In theST000054 public database (Metabolic Workbench) we observed that the mammary TM were enriched with cholesterol (1.9 times respected to reduction breast samples, p-value <0.01).Our goal is to understand how oncology relevant factors could alter TM metabolism. In previous studies, we demonstrated that TNF increased the triglyceride secretion and altered the pattern of fatty acid secretion. Therefore, we were interested in studying the regulation of lipid metabolism by an anti-inflammatory stimulus.We observed by gas chromatography that the pattern of secreted fatty acids was altered in murine mammary gland adipose tissue conditioned media (C57BL-6j) after 48 h with or without dexamethasone (Dx) 500 nM. Among them, the proportion of palmitic acid increased (32.54% Dx vs 3.02% control). We also observed an enrichment of saturated fatty acids under Dx stimulus similarly of what we have seen with TNF (66.1% Dx, 30.3% TNF, 5.3% control).To further understand this result, we analysed with GEO2R the gene expression from GSE62635 database where adipocyte differentiated 3T3-L1 were treated with Dx 500 nM for 6 days and then we studied pathways enrichment with the String platform. In the set of genes with a fold change<-1.5 and an adj.p.value<0.01, we identified the pathways described in KEGG as Unsaturated fatty acid biosynthesis (mmu01040, FDR=0.0014). Based on these data, we studied in depth each gene involved in this pathway and observed a correlation between the downregulation of the genes involved in the pathway and the enrichment of saturated fatty acids found in the conditioned media.These results encourage us to deepen our studies of the metabolic adaptation of cells in the tumor microenvironment to anti-inflammatory stimuli and how it can impact the metabolism of tumor cells.