Metabolome analysis reveals that cyclic adenosine diphosphate ribose contributes to the regulation of differentiation in mice adipocyte

Adipocytes play a key role in energy storage and homeostasis. Although the role of transcription factors in adipocyte differentiation is known, the effect of endogenous metabolites of low molecular weight remains unclear. Here, we analyzed time-dependent changes in the levels of these metabolites throughout adipocyte differentiation, using metabolome analysis, and demonstrated that there is a positive correlation between cyclic adenosine diphosphate ribose (cADPR) and Ppar gamma mRNA expression used as a marker of differentiation. We also found that the treatment of C3H10T1/2 adipocytes with cADPR increased the mRNA expression of those marker genes and the accumulation of triglycerides. Furthermore, inhibition of ryanodine receptors (RyR), which are activated by cADPR, caused a significant reduction in mRNA expression levels of the marker genes and triglyceride accumulation in adipocytes. Our findings show that cADPR accelerates adipocytic differentiation via RyR pathway. We generated several immortalized adipocytes from mouse adipose tissue. We have revealed that a large number of metabolites in these cells change during adipogenesis by metabolome analysis. Furthermore, we found that cyclic adenosine diphosphate ribose (cADPR) regulates adipocyte differentiation via ryanodine receptors (RyR) by analyzing the correlation between differentiation-related gene expression level and metabolites.image