Caloric restriction increases levels of taurine in the intestine and stimulates taurine uptake by conjugation to glutathione

Gregor, András; Pignitter, Marc; Fahrngruber, Christine; Bayer, Sebastian; Somoza, Veronika; König, Jürgen; Duszka, Kalina

doi:10.1016/j.jnutbio.2021.108781

Cited by 13 publications

(30 citation statements)

References 60 publications

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“…Six parts of the GI tract tissues were analyzed, with 7-14 samples extracted from each tissue. Details about the RNA isolation from intestinal scrapings samples, genes, PCR primers, and quantitative PCR (qRT-PCR) reaction are presented in our publications [15,32] and Suppl. Methods Section 6.7.…”

Section: Qpcr Data Analysis Across Gastrointestinal (Gi) Tract Tissuesmentioning

confidence: 99%

“…To compare CR-induced DEG patterns in mucosa of the different GI tract tissues, we selected 18 DM DEGs which respond to CR representing epithelial cell metabolism, immune system cells and pro-oncogenic/cancer-associated expression genes. Table S10A shows the list of the DEGs for immune system (Stat1, Tlr3, Irf1, Reg3b, Reg3g, Oas1a) and metabolism (Acot4, Acox2, Scd1, Cd36, Pparα, Vldlr, Gsta3, Gsta4, Mgst1, Mgst2) defined by qPCR in stomach, duodenum, jejunum, ileum, proximal and distal colon [15,32]. Six parts of the GI tract tissues were analyzed, with 7-14 samples extracted from each tissue.…”

Section: Dm Microarray-defined Deg and Gi Tract Tissue Samples Qpcr Analysis Suggests Correlated Positional Expression Patterns Of Cr-indmentioning

confidence: 99%

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Immunity Depletion, Telomere Imbalance, and Cancer-Associated Metabolism Pathway Aberrations in Intestinal Mucosa upon Short-Term Caloric Restriction

Maestri

Duszka

Kuznetsov

2021

Cancers

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Systems cancer biology analysis of calorie restriction (CR) mechanisms and pathways has not been carried out, leaving therapeutic benefits unclear. Using metadata analysis, we studied gene expression changes in normal mouse duodenum mucosa (DM) response to short-term (2-weeks) 25% CR as a biological model. Our results indicate cancer-associated genes consist of 26% of 467 CR responding differential expressed genes (DEGs). The DEGs were enriched with over-expressed cell cycle, oncogenes, and metabolic reprogramming pathways that determine tissue-specific tumorigenesis, cancer, and stem cell activation; tumor suppressors and apoptosis genes were under-expressed. DEG enrichments suggest telomeric maintenance misbalance and metabolic pathway activation playing dual (anti-cancer and pro-oncogenic) roles. The aberrant DEG profile of DM epithelial cells is found within CR-induced overexpression of Paneth cells and is coordinated significantly across GI tract tissues mucosa. Immune system genes (ISGs) consist of 37% of the total DEGs; the majority of ISGs are suppressed, including cell-autonomous immunity and tumor-immune surveillance. CR induces metabolic reprogramming, suppressing immune mechanics and activating oncogenic pathways. We introduce and argue for our network pro-oncogenic model of the mucosa multicellular tissue response to CR leading to aberrant transcription and pre-malignant states. These findings change the paradigm regarding CR’s anti-cancer role, initiating specific treatment target development. This will aid future work to define critical oncogenic pathways preceding intestinal lesion development and biomarkers for earlier adenoma and colorectal cancer detection.

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Section: Qpcr Data Analysis Across Gastrointestinal (Gi) Tract Tissuesmentioning

confidence: 99%

Section: Dm Microarray-defined Deg and Gi Tract Tissue Samples Qpcr Analysis Suggests Correlated Positional Expression Patterns Of Cr-indmentioning

confidence: 99%

Immunity Depletion, Telomere Imbalance, and Cancer-Associated Metabolism Pathway Aberrations in Intestinal Mucosa upon Short-Term Caloric Restriction

Maestri

Duszka

Kuznetsov

2021

Cancers

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“…Our recent original study indicated that the liver in CR animals shows increased mRNA expression of cysteine dioxygenase (CDO), an enzyme responsible for the metabolism of cysteine to taurine. 37 The CR animals also show enhanced expression of Cyp7a1, Ntcp (Na + /taurocholate cotransporting polypeptide), which are necessary for BA synthesis and transport. Further, we demonstrated that CR results in increased levels of taurine-conjugated BAs in the intestinal content and mucosa.…”

Section: Introductionmentioning

confidence: 99%

“…Further, we demonstrated that CR results in increased levels of taurine-conjugated BAs in the intestinal content and mucosa. 14 , 37 BAs in the intestine undergo deconjugation and this leads to high levels of free taurine. Simultaneously, CR stimulates the expression and activity of glutathione (GSH) S-transferases (GST) that conjugate taurine leading to an increase in GSH-taurine conjugate levels.…”

Section: Introductionmentioning

confidence: 99%

“…The occurrence of GSH-taurine conjugate in conjunction with CR triggers enhanced intestinal uptake of taurine. 37 Knowing the vast role of gut bacteria in the metabolism of BAs, we hypothesized that microbiota may contribute to the CR-triggered phenomena. Here, we present novel results showing that microbiota is required for the CR-triggered phenotype associated with GSH and taurine conjugation as well as intestinal uptake.…”

Section: Introductionmentioning

confidence: 99%

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Microbial contribution to the caloric restriction-triggered regulation of the intestinal levels of glutathione transferases, taurine, and bile acid

et al. 2021

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Recently we showed that caloric restriction (CR) triggers an increase in the levels of free taurine, taurine-conjugated bile acids (BA), and other taurine conjugates in intestinal mucosa while decreasing glutathione (GSH) levels in wild-type male mice. In the current project, we decided to investigate whether the microbiota is involved in the response to CR by depleting gut bacteria. The antibiotics treatment diminished CR-specific increase in the levels of free taurine and its conjugates as well as upregulated expression and activity of GSH transferases (GST) in the intestinal mucosa. Further, it diminished a CR-related increase in BAs levels in the liver, plasma, and intestinal mucosa. Transplant of microbiota from CR mice to ad libitum fed mice triggered CR-like changes in MGST1 expression, levels of taurine and taurine conjugates in the mucosa of the ileum. We show for the first time, that microbiota contributes to the intestinal response to CR-triggered changes in BA, taurine, and GST levels.

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Fiber consumption stimulates the activity of microbial bile salt hydrolases

Gregor,

Auernigg-Haselmaier,

Malleier

et al. 2023

Journal of Functional Foods

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Caloric restriction increases levels of taurine in the intestine and stimulates taurine uptake by conjugation to glutathione

Cited by 13 publications

References 60 publications

Immunity Depletion, Telomere Imbalance, and Cancer-Associated Metabolism Pathway Aberrations in Intestinal Mucosa upon Short-Term Caloric Restriction

Immunity Depletion, Telomere Imbalance, and Cancer-Associated Metabolism Pathway Aberrations in Intestinal Mucosa upon Short-Term Caloric Restriction

Microbial contribution to the caloric restriction-triggered regulation of the intestinal levels of glutathione transferases, taurine, and bile acid

Fiber consumption stimulates the activity of microbial bile salt hydrolases

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