Signaling Pathway of Taurine-Induced Upregulation of TXNIP.

Taurine, a sulfur-containing ß-amino acid, is present at high concentrations in mammalian tissues and plays an important role in several essential biological processes. However, the genetic mechanisms involved in these physiological processes associated with taurine remain unclear. In this study, we investigated the regulatory mechanism underlying the taurine-induced transcriptional enhancement of the thioredoxin-interacting protein (TXNIP). The results showed that taurine significantly increased the luciferase activity of the human TXNIP promoter. Further, deletion analysis of the TXNIP promoter showed that taurine induced luciferase activity only in the TXNIP promoter region (+200 to +218). Furthermore, by employing a bioinformatic analysis using the TRANSFAC database, we focused on Tst-1 and Ets-1 as candidates involved in taurine-induced transcription and found that the mutation in the Ets-1 sequence did not enhance transcriptional activity by taurine. Additionally, chromatin immunoprecipitation assays indicated that the binding of Ets-1 to the TXNIP promoter region was enhanced by taurine. Taurine also increased the levels of phosphorylated Ets-1, indicating activation of Ets-1 pathway by taurine. Moreover, an ERK cascade inhibitor significantly suppressed the taurine-induced increase in TXNIP mRNA levels and transcriptional enhancement of TXNIP. These results suggest that taurine enhances TXNIP expression by activating transcription factor Ets-1 via the ERK cascade.

Taurine is an amino acid with the ability to activate autophagy in adipocytes.

Alterations in adipocyte characteristics are highly implicated in the pathology of obesity. In a recent article, we demonstrated that high-fat diet-induced obesity impairs lysosomal function, thereby suppressing autophagy in mice white adipose tissue. Taurine, an amino acid naturally contained in the normal diet and existing ubiquitously in tissues, has been reported to improve insulin resistance and chronic inflammation in animal models, but underlying mechanisms remain unclear. From these findings, we hypothesized that improvement of obese pathology by taurine may be mediated through recovery of autophagy. In matured 3T3-L1 mouse adipocytes, treatment with taurine-promoted autophagy. Moreover, taurine-induced nuclear translocation of transcription factor EB (TFEB), a master regulator of autophagy- and lysosome-related factors. As this translocation is regulated by several kinase pathways, including extracellular signal-related kinase 1 and 2 (ERK1/2) and mechanistic target of rapamycin protein kinase complex 1 (MTORC1), we examined related signaling elements. Consequently, taurine-reduced phosphorylation levels of ERK1/2 but did not alter the phosphorylation of MTORC1 pathway-associated adenosine monophosphate-activated protein kinase or ribosomal protein S6 kinase. Taken together, these results suggest that taurine may enhance TFEB nuclear translocation through ERK1/2 to accelerate autophagy. The effect discovered in this study may represent a novel mechanism for the improvement of obesity-related pathology by taurine.

Potential role of taurine in the prevention of diabetes and metabolic syndrome.

Metabolic syndrome is characterized by the cluster of a number of metabolic abnormalities in the presence of underlying insulin resistance. The prevalence of metabolic syndrome has steadily increased in all populations worldwide. Taurine (2-aminoethanesulfonic acid) is a sulfur-containing amino acid that is involved in a variety of physiological functions. Clinical and experimental studies show that taurine intake may be beneficial in the prevention of metabolic syndrome including diabetes, obesity, dyslipidemia, and hypertension. This article reviews the effect of taurine on all of the components of metabolic syndrome. In addition, the possible mechanisms by which taurine prevents diabetes and metabolic syndrome are also discussed. Further study is needed to determine the role of taurine in the development of metabolic syndrome in humans, because there is presently limited clinical data available.