multiple intracellular signaling pathways orchestrate adipocytic differentiation of human bone marrow stromal stem cells bone marrow adipocyte formation plays a role in bone homeostasis and whole body energy metabolism however the transcriptional landscape and signaling pathways associated with adipocyte lineage commitment and maturation are not fully delineated thus we performed global gene expression profiling during adipocyte differentiation of human bone marrow stromal mesenchymal stem cells hmscs and identified 2589 upregulated and 2583 downregulated mrna transcripts pathway analysis on the upregulated gene list untraveled enrichment in multiple signaling pathways including insulin receptor signaling focal adhesion metapathway biotransformation a number of metabolic pathways eg selenium metabolism benzoapyrene metabolism fatty acid triacylglycerol ketone body metabolism tryptophan metabolism and catalytic cycle of mammalian flavincontaining monooxygenase fmos on the other hand pathway analysis on the downregulated genes revealed significant enrichment in pathways related to cell cycle regulation based on these data we assessed the effect of pharmacological inhibition of fak signaling using pf573228 pf562271 and insrigf1r using nvpaew541 and gsk1904529a on adipocyte differentiation hmscs exposed to fak or igf1rinsr inhibitors exhibited fewer adipocyte formation 2758 inhibition p0005 concordantly the expression of adipocytespecific genes ap2 adipoq and cebp was significantly reduced on the other hand we did not detect significant effects on cell viability as a result of fak or igf1rinsr inhibition our data identified fak and insulin signaling as important intracellular signaling pathways relevant to bone marrow adipogenesis