Abstract
Taurine, which is abundant in mammalian tissues, especially in the heart, is essential for cellular osmoregulation. We previously reported that taurine deficiency leads to changes in the levels of several metabolites, suggesting that alterations in those metabolites might compensate in part for tissue taurine loss, a process that would be important in maintaining cardiac homeostasis. In this study, we investigated the molecular basis for changes in the metabolite profile of a taurine-deficient heart using pathway analysis based on the transcriptome and metabolome profile in the hearts of taurine transporter knockout mice (TauTKO mice), which have been reported by us. First, the genes associated with transport activity, such as the solute carrier (SLC) family, are increased in TauTKO mice, while the established transporters for metabolites that are elevated in the TauTKO heart, such as betaine and carnitine, are not altered by taurine deficiency. Second, the integrated analysis using transcriptome and metabolome data revealed significant increases and/or decreases in the genes involved in Arginine metabolism, Ketone body degradation, Glycerophospholipid metabolism, and Fatty acid metabolism in the KEGG pathway database. In conclusion, these pathway analyses revealed genetic compensatory mechanisms involved in the control of the metabolome profile of the taurine-deficient heart.
Highlights
Taurine is abundant in mammalian tissue, especially in excitable tissues, such as the heart.Taurine functions as a compatible organic osmolyte, thereby assisting in the regulation of intracellular osmotic balance as well as betaine, glycerophosphocholine (GPC), sorbitol, free amino acids, etc. [1]
We previously demonstrated that knocking out the taurine transporter (TauT; Slc6a6) of mice (TauTKO mice) caused a taurine-deficient cardiomyopathy characterized by ventricular wall thinning and induction of heart failure marker genes [4]
The metabolome data set used in the analysis consists of the metabolites that have a variable importance in projection (VIP) score calculated by partial least squares discriminant analysis (PLS-DA) greater than 1 and/or a p value calculated by Mann–Whitney U test less than 0.05
Summary
Taurine is abundant in mammalian tissue, especially in excitable tissues, such as the heart.Taurine functions as a compatible organic osmolyte, thereby assisting in the regulation of intracellular osmotic balance as well as betaine ( called glycine betaine), glycerophosphocholine (GPC), sorbitol, free amino acids, etc. [1]. Taurine is abundant in mammalian tissue, especially in excitable tissues, such as the heart. Taurine possesses various cellular actions, such as modulation of ion movement and calcium handling [2]. Maintenance of certain species, such as cats, on a taurine-deficient diet leads to development of dilated cardiomyopathy [3]. We previously demonstrated that knocking out the taurine transporter (TauT; Slc6a6) of mice (TauTKO mice) caused a taurine-deficient cardiomyopathy characterized by ventricular wall thinning and induction of heart failure marker genes [4]. Despite the severe depletion of taurine (less than 1% of wild-type mice), cardiac output is normal in the young animal it declines with age. The mild condition of the TauTKO phenotype may relate to homeostatic mechanisms that compensate for detrimental effects caused by taurine depletion
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