Taurine is one of the most abundant free amino acids in heart, and its treatment is beneficial against chronic heart failure. While knocking out taurine transporter (TauT) in mice caused a taurine-deficient cardiomyopathy, cardiac output is normal in the young TauTKO mouse, suggesting activation of homeostatic mechanisms that compensate for detrimental effects caused by taurine depletion. In the present study, we examined the integrated analysis of transcriptome and metabolome of TauTKO mice to determine the compensatory homeostatic pathway. We identified increases in several organic osmolytes, including betaine, carnitine, glycerophosphocholine (GPC) and amino acids, in the heart of TauTKO mice. Transcriptome analysis revealed that several genes of the SLC transporter family are increased in TauTKO mice, such as amino acid transporter (Slc38a2), while the established transporters for betaine and carnitine are not altered by taurine deficiency. The integrated analysis revealed a significant increase in the genes involved in Glycerophospholipid metabolism in which GPC biosynthesis is involved. In conclusion, we identified genetic/metabolic compensatory mechanisms involved in the control of the metabolome profile in taurine-deficient cardiomyopathy.

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