Cancer SLC6A6-mediated taurine uptake transactivates immune checkpoint genes and induces exhaustion in CD8+ T cells.

Taurine is used to bolster immunity, but its effects on antitumor immunity are unclear. Here, we report that cancer-related taurine consumption causes T cell exhaustion and tumor progression. The taurine transporter SLC6A6 is correlated with aggressiveness and poor outcomes in multiple cancers. SLC6A6-mediated taurine uptake promotes the malignant behaviors of tumor cells but also increases the survival and effector function of CD8+ T cells. Tumor cells outcompete CD8+ T cells for taurine by overexpressing SLC6A6, which induces T cell death and malfunction, thereby fueling tumor progression. Mechanistically, taurine deficiency in CD8+ T cells increases ER stress, promoting ATF4 transcription in a PERK-JAK1-STAT3 signaling-dependent manner. Increased ATF4 transactivates multiple immune checkpoint genes and induces T cell exhaustion. In gastric cancer, we identify a chemotherapy-induced SP1-SLC6A6 regulatory axis. Our findings suggest that tumoral-SLC6A6-mediated taurine deficiency promotes immune evasion and that taurine supplementation reinvigorates exhausted CD8+ T cells and increases the efficacy of cancer therapies.

Glycyl Radical Enzymes and Sulfonate Metabolism in the Microbiome.

Sulfonates include diverse natural products and anthropogenic chemicals and are widespread in the environment. Many bacteria can degrade sulfonates and obtain sulfur, carbon, and energy for growth, playing important roles in the biogeochemical sulfur cycle. Cleavage of the inert sulfonate C-S bond involves a variety of enzymes, cofactors, and oxygen-dependent and oxygen-independent catalytic mechanisms. Sulfonate degradation by strictly anaerobic bacteria was recently found to involve C-S bond cleavage through O2-sensitive free radical chemistry, catalyzed by glycyl radical enzymes (GREs). The associated discoveries of new enzymes and metabolic pathways for sulfonate metabolism in diverse anaerobic bacteria have enriched our understanding of sulfonate chemistry in the anaerobic biosphere. An anaerobic environment of particular interest is the human gut microbiome, where sulfonate degradation by sulfate- and sulfite-reducing bacteria (SSRB) produces H2S, a process linked to certain chronic diseases and conditions.

PTER is a N-acetyltaurine hydrolase that regulates feeding and obesity.

Taurine is a conditionally essential micronutrient and one of the most abundant amino acids in humans1-3. In endogenous taurine metabolism, dedicated enzymes are involved in the biosynthesis of taurine from cysteine and in the downstream metabolism of secondary taurine metabolites4,5. One taurine metabolite is N-acetyltaurine6. Levels of N-acetyltaurine are dynamically regulated by stimuli that alter taurine or acetate flux, including endurance exercise7, dietary taurine supplementation8 and alcohol consumption6,9. So far, the identities of the enzymes involved in N-acetyltaurine metabolism, and the potential functions of N-acetyltaurine itself, have remained unknown. Here we show that the body mass index associated orphan enzyme phosphotriesterase-related (PTER)10 is a physiological N-acetyltaurine hydrolase. In vitro, PTER catalyses the hydrolysis of N-acetyltaurine to taurine and acetate. In mice, PTER is expressed in the kidney, liver and brainstem. Genetic ablation of Pter in mice results in complete loss of tissue N-acetyltaurine hydrolysis activity and a systemic increase in N-acetyltaurine levels. After stimuli that increase taurine levels, Pter knockout mice exhibit reduced food intake, resistance to diet-induced obesity and improved glucose homeostasis. Administration of N-acetyltaurine to obese wild-type mice also reduces food intake and body weight in a GFRAL-dependent manner. These data place PTER into a central enzymatic node of secondary taurine metabolism and uncover a role for PTER and N-acetyltaurine in body weight control and energy balance.

Huayu Qutan Recipe promotes lipophagy and cholesterol efflux through the mTORC1/TFEB/ABCA1-SCARB1 signal axis.

This study aims to investigate the mechanism of the anti-atherosclerosis effect of Huayu Qutan Recipe (HYQT) on the inhibition of foam cell formation. In vivo, the mice were randomly divided into three groups: CTRL group, MOD group and HYQT group. The HYQT group received HYQT oral administration twice a day (20.54 g/kg/d), and the plaque formation in ApoE-/- mice was observed using haematoxylin-eosin (HE) staining and oil red O (ORO) staining. The co-localization of aortic macrophages and lipid droplets (LDs) was examined using fluorescent labelling of CD11b and BODIPY fluorescence probe. In vitro, RAW 264.7 cells were exposed to 50 µg/mL ox-LDL for 48 h and then treated with HYQT for 24 h. The accumulation of LDs was evaluated using ORO and BODIPY. Cell viability was assessed using the CCK-8 assay. The co-localization of LC3b and BODIPY was detected via immunofluorescence and fluorescence probe. LysoTracker Red and BODIPY 493/503 were used as markers for lysosomes and LDs, respectively. Autophagosome formation were observed via transmission electron microscopy. The levels of LC3A/B II/LC3A/B I, p-mTOR/mTOR, p-4EBP1/4EBP1, p-P70S6K/P70S6K and TFEB protein level were examined via western blotting, while SQSTM1/p62, Beclin1, ABCA1, ABCG1 and SCARB1 were examined via qRT-PCR and western blotting. The nuclear translocation of TFEB was detected using immunofluorescence. The components of HYQT medicated serum were determined using Q-Orbitrap high-resolution MS analysis. Molecular docking was employed to identify the components of HYQT medicated serum responsible for the mTOR signalling pathway. The mechanism of taurine was illustrated. HYQT has a remarkable effect on atherosclerotic plaque formation and blood lipid level in ApoE-/- mice. HYQT decreased the co-localization of CD11b and BODIPY. HYQT (10% medicated serum) reduced the LDs accumulation in RAW 264.7 cells. HYQT and RAPA (rapamycin, a mTOR inhibitor) could promote cholesterol efflux, while chloroquine (CQ, an autophagy inhibitor) weakened the effect of HYQT. Moreover, MHY1485 (a mTOR agonist) also mitigated the effects of HYQT by reduced cholesterol efflux. qRT-PCR and WB results suggested that HYQT improved the expression of the proteins ABCA1, ABCG1 and SCARB1.HYQT regulates ABCA1 and SCARB1 protein depending on the mTORC1/TFEB signalling pathway. However, the activation of ABCG1 does not depend on this pathway. Q-Orbitrap high-resolution MS analysis results demonstrated that seven core compounds have good binding ability to the mTOR protein. Taurine may play an important role in the mechanism regulation. HYQT may reduce cardiovascular risk by promoting cholesterol efflux and degrading macrophage-derived foam cell formation. It has been observed that HYQT and ox-LDL regulate lipophagy through the mTOR/TFEB signalling pathway, rather than the mTOR/4EBP1/P70S6K pathway. Additionally, HYQT is found to regulate cholesterol efflux through the mTORC1/TFEB/ABCA1-SCARB1 signal axis, while taurine plays a significant role in lipophagy.

Isethionate is an intermediate in the degradation of sulfoacetate by the human gut pathobiont Bilophila wadsworthia.

The obligately anaerobic sulfite-reducing bacterium Bilophila wadsworthia is a common human pathobiont inhabiting the distal intestinal tract. It has a unique ability to utilize a diverse range of food- and host-derived sulfonates to generate sulfite as a terminal electron acceptor (TEA) for anaerobic respiration, converting the sulfonate sulfur to H2S, implicated in inflammatory conditions and colon cancer. The biochemical pathways involved in the metabolism of the C2 sulfonates isethionate and taurine by B. wadsworthia were recently reported. However, its mechanism for metabolizing sulfoacetate, another prevalent C2 sulfonate, remained unknown. Here, we report bioinformatics investigations and in vitro biochemical assays that uncover the molecular basis for the utilization of sulfoacetate as a source of TEA (STEA) for B. wadsworthia, involving conversion to sulfoacetyl-CoA by an ADP-forming sulfoacetate-CoA ligase (SauCD), and stepwise reduction to isethionate by NAD(P)H-dependent enzymes sulfoacetaldehyde dehydrogenase (SauS) and sulfoacetaldehyde reductase (TauF). Isethionate is then cleaved by the O2-sensitive isethionate sulfolyase (IseG), releasing sulfite for dissimilatory reduction to H2S. Sulfoacetate in different environments originates from anthropogenic sources such as detergents, and natural sources such as bacterial metabolism of the highly abundant organosulfonates sulfoquinovose and taurine. Identification of enzymes for anaerobic degradation of this relatively inert and electron-deficient C2 sulfonate provides further insights into sulfur recycling in the anaerobic biosphere, including the human gut microbiome.

Taurine modulates host cell responses to Helicobacter pylori VacA toxin.

Colonization of the human stomach with Helicobacter pylori strains producing active forms of the secreted toxin VacA is associated with an increased risk of peptic ulcer disease and gastric cancer, compared with colonization with strains producing hypoactive forms of VacA. Previous studies have shown that active s1m1 forms of VacA cause cell vacuolation and mitochondrial dysfunction. In this study, we sought to define the cellular metabolic consequences of VacA intoxication. Untargeted metabolomic analyses revealed that several hundred metabolites were significantly altered in VacA-treated gastroduodenal cells (AGS and AZ-521) compared with control cells. Pathway analysis suggested that VacA caused alterations in taurine and hypotaurine metabolism. Treatment of cells with the purified active s1m1 form of VacA, but not hypoactive s2m1 or Δ6-27 VacA-mutant proteins (defective in membrane channel formation), caused reductions in intracellular taurine and hypotaurine concentrations. Supplementation of the tissue culture medium with taurine or hypotaurine protected AZ-521 cells against VacA-induced cell death. Untargeted global metabolomics of VacA-treated AZ-521 cells or AGS cells in the presence or absence of extracellular taurine showed that taurine was the main intracellular metabolite significantly altered by extracellular taurine supplementation. These results indicate that VacA causes alterations in cellular taurine metabolism and that repletion of taurine is sufficient to attenuate VacA-induced cell death. We discuss these results in the context of previous literature showing the important role of taurine in cell physiology and the pathophysiology or treatment of multiple pathologic conditions, including gastric ulcers, cardiovascular disease, malignancy, inflammatory diseases, and other aging-related disorders.

Altered brain metabolites in male nonhuman primate offspring exposed to maternal immune activation.

Converging data show that exposure to maternal immune activation (MIA) in utero alters brain development in animals and increases the risk of neurodevelopmental disorders in humans. A recently developed non-human primate MIA model affords opportunities for studies with uniquely strong translational relevance to human neurodevelopment. The current longitudinal study used 1H-MRS to investigate the developmental trajectory of prefrontal cortex metabolites in male rhesus monkey offspring of dams (n = 14) exposed to a modified form of the inflammatory viral mimic, polyinosinic:polycytidylic acid (Poly IC), in the late first trimester. Brain metabolites in these animals were compared to offspring of dams that received saline (n = 10) or no injection (n = 4). N-acetylaspartate (NAA), glutamate, creatine, choline, myo-inositol, taurine, and glutathione were estimated from PRESS and MEGA-PRESS acquisitions obtained at 6, 12, 24, 36, and 45 months of age. Prior investigations of this cohort reported reduced frontal cortical gray and white matter and subtle cognitive impairments in MIA offspring. We hypothesized that the MIA-induced neurodevelopmental changes would extend to abnormal brain metabolite levels, which would be associated with the observed cognitive impairments. Prefrontal NAA was significantly higher in the MIA offspring across all ages (p < 0.001) and was associated with better performance on the two cognitive measures most sensitive to impairment in the MIA animals (both p < 0.05). Myo-inositol was significantly lower across all ages in MIA offspring but was not associated with cognitive performance. Taurine was elevated in MIA offspring at 36 and 45 months. Glutathione did not differ between groups. MIA exposure in male non-human primates is associated with altered prefrontal cortex metabolites during childhood and adolescence. A positive association between elevated NAA and cognitive performance suggests the hypothesis that elevated NAA throughout these developmental stages reflects a protective or resilience-related process in MIA-exposed offspring. The potential relevance of these findings to human neurodevelopmental disorders is discussed.

Improvement of diabetes-induced spinal cord axon injury with taurine via nerve growth factor-dependent Akt/mTOR pathway.

Diabetic neuropathy (DN) is a common neurological complication caused by diabetes mellitus (DM). Axonal degeneration is generally accepted to be the major pathological change in peripheral DN. Taurine has been evidenced to be neuroprotective in various aspects, but its effect on spinal cord axon injury (SCAI) in DN remains barely reported. This study showed that taurine significantly ameliorated axonal damage of spinal cord (SC), based on morphological and functional analyses, in a rat model of DN induced by streptozotocin (STZ). Taurine was also found to induce neurite outgrowth in cultured cerebral cortex neurons with high glucose exposure. Moreover, taurine up-regulated the expression of nerve growth factor (NGF) and neurite outgrowth relative protein GAP-43 in rat DN model and cultured cortical neurons/VSC4.1 cells. Besides, taurine increased the activating phosphorylation signals of TrkA, Akt, and mTOR. Mechanistically, the neuroprotection by taurine was related to the NGF-pAKT-mTOR axis, because either NGF-neutralizing antibody or Akt or mTOR inhibitors was found to attenuate its beneficial effects. Together, our results demonstrated that taurine promotes spinal cord axon repair in a model of SCAI in STZ-induced diabetic rats, mechanistically associating with the NGF-dependent activation of Akt/mTOR pathway.

Taurine deficiency associated with dilated cardiomyopathy and aging.

Taurine (2-aminoethanesulfonic acid) is a free amino acid found ubiquitously and abundantly in mammalian tissues. Taurine content in the heart is approximately 20 mM, which is approximately 100 times higher than plasma concentration. The high intracellular concentration of taurine is maintained by the taurine transporter (TauT; Slc6a6). Taurine plays various roles, including the regulation of intracellular ion dynamics, calcium handling, and acting as an antioxidant in the heart. Some species, such as cats and foxes, have low taurine biosynthetic capacity, and dietary taurine deficiency can lead to disorders such as dilated cardiomyopathy and blindness. In humans, the relationship between dietary taurine deficiency and cardiomyopathy is not yet clear, but a genetic mutation related to the taurine transporter has been reported to be associated with dilated cardiomyopathy. On the other hand, many studies have shown an association between dietary taurine intake and age-related diseases. Notably, it has recently been reported that taurine declines with age and is associated with lifespan in worms and mice, as well as healthspan in mice and monkeys. In this review, we summarize the role of dietary and genetic taurine deficiency in the development of cardiomyopathy and aging.

Identification of a novel enzyme and the regulation of key enzymes in mammalian taurine synthesis.

Taurine has many pharmacological roles on various tissues. The maintenance of abundant taurine content in the mammalian body through endogenous synthesis, in addition to exogenous intake, is the essential factor for morphological and functional maintenances in most tissues. The synthesis of taurine from sulfur-containing amino acids is influenced by various factors. Previous literature findings indicate the influence of the intake of proteins and sulfur-containing amino acids on the activity of the rate-limiting enzymes cysteine dioxygenase and cysteine sulfinate decarboxylase. In addition, the regulation of the activity and expression of taurine-synthesis enzymes by hormones, bile acids, and inflammatory cytokines through nuclear receptors have been reported in liver and reproductive tissues. Furthermore, flavin-containing monooxygenase subtype 1 was recently identified as the taurine-synthesis enzyme that converts hypotaurine to taurine. This review introduces the novel taurine synthesis enzyme and the nuclear receptor-associated regulation of key enzymes in taurine synthesis.

MS4A1-PTGS2 axis induces taurine metabolic reprogramming to exacerbate abdominal aortic aneurysm progression.

This study unveils the pivotal roles of taurine metabolic reprogramming and its implications in the development and progression of Abdominal Aortic Aneurysm (AAA). Leveraging an integrated approach that combines single-cell RNA sequencing (scRNA-seq) and Weighted Gene Co-expression Network Analysis (WGCNA), our research investigates the intricate transcriptional and gene expression dynamics crucial to AAA. Our findings uniquely link metabolic shifts to the integrity of the extracellular matrix (ECM) and the functionality of smooth muscle cells (SMCs), key elements in the pathology of AAA. Utilizing scRNA-seq data from a mouse model (GSE152583 dataset), we identified critical alterations in cellular composition during AAA progression, particularly highlighting shifts in fibroblasts and inflammatory cells. Concurrently, WGCNA of human AAA tissue samples has outlined distinct gene expression patterns correlated with disease severity and progression, offering comprehensive insights into both molecular and cellular disease mechanisms. Moreover, this study introduces innovative metabolic profiling techniques to identify differential metabolites in AAA, integrating extensive metabolomic analyses with pathway enrichment strategies. This novel approach has pinpointed potential biomarkers and therapeutic targets, notably within taurine metabolism pathways, crucial for crafting non-surgical interventions. By merging state-of-the-art bioinformatics with thorough molecular analysis, our study not only enhances the understanding of AAA's complex pathophysiology but also catalyzes the development of targeted therapeutic strategies. This research represents a significant advancement in the molecular characterization of AAA, with substantial implications for its future diagnosis and treatment strategies.

Exogenous taurine administration abates reproductive dysfunction in male rats exposed to silver nanoparticles.

The broad contemporary applications of silver nanoparticles (AgNPs) have been associated with various toxicities including reproductive toxicity. Taurine is well acknowledged for its potent pharmacological role in numerous disease models and chemically-mediated toxicity. We investigated the effect of taurine on AgNPs-induced reproductive toxicity in male rats. The animals were intraperitoneally injected with AgNPs (200 µg/kg) alone or co-administered with taurine at 50 and 100 mg/kg for 21 successive days. Exogenous taurine administration significantly abated AgNPs-induced oxidative injury by decreasing the levels of oxidative stress indices while boosting antioxidant enzymes activities and glutathione level in the hypothalamus, testes and epididymis of exposed animals. Taurine administration alleviated AgNPs-induced inflammatory response and caspase-3 activity, an apoptotic biomarker. Moreover, taurine significantly improved spermiogram, reproductive hormones and the marker enzymes of testicular function in AgNPs-treated animals. The ameliorative effect of taurine on pathological lesions induced by AgNPs in the exposed animals was substantiated by histopathological data. This study provides the first mechanistic evidence that taurine supplementation affords therapeutic effect against reproductive dysfunction associated with AgNPs exposure in male rats.

Identification of bile acid-CoA:amino acid N-acyltransferase as the hepatic N-acyl taurine synthase for polyunsaturated fatty acids.

N-acyl taurines (NATs) are bioactive lipids with emerging roles in glucose homeostasis and lipid metabolism. The acyl chains of hepatic and biliary NATs are enriched in polyunsaturated fatty acids (PUFAs). Dietary supplementation with a class of PUFAs, the omega-3 fatty acids, increases their cognate NATs in mice and humans. However, the synthesis pathway of the PUFA-containing NATs remains undiscovered. Here, we report that human livers synthesize NATs and that the acyl-chain preference is similar in murine liver homogenates. In the mouse, we found that hepatic NAT synthase activity localizes to the peroxisome and depends upon an active-site cysteine. Using unbiased metabolomics and proteomics, we identified bile acid-CoA:amino acid N-acyltransferase (BAAT) as the likely hepatic NAT synthase in vitro. Subsequently, we confirmed that BAAT knockout livers lack up to 90% of NAT synthase activity and that biliary PUFA-containing NATs are significantly reduced compared with wildtype. In conclusion, we identified the in vivo PUFA-NAT synthase in the murine liver and expanded the known substrates of the bile acid-conjugating enzyme, BAAT, beyond classic bile acids to the synthesis of a novel class of bioactive lipids.

Mammalian monocarboxylate transporter 7 (MCT7/Slc16a6) is a novel facilitative taurine transporter.

Monocarboxylate transporter 7 (MCT7) is an orphan transporter expressed in the liver, brain, and in several types of cancer cells. It has also been reported to be a survival factor in melanoma and breast cancers. However, this survival mechanism is not yet fully understood due to MCT7's unidentified substrate(s). Therefore, here we sought to identify MCT7 substrate(s) and characterize the transport mechanisms by analyzing amino acid transport in HEK293T cells and polarized Caco-2 cells. Analysis of amino acids revealed significant rapid reduction in taurine from cells transfected with enhanced green fluorescent protein-tagged MCT7. We found that taurine uptake and efflux by MCT7 was pH-independent and that the uptake was not saturated in the presence of taurine excess of 200 mM. Furthermore, we found that monocarboxylates and acidic amino acids inhibited MCT7-mediated taurine uptake. These results imply that MCT7 may be a low-affinity facilitative taurine transporter. We also found that MCT7 was localized at the basolateral membrane in polarized Caco-2 cells and that the induction of MCT7 expression in polarized Caco-2 cells enhanced taurine permeation. Finally, we demonstrated that interactions of MCT7 with ancillary proteins basigin/CD147 and embigin/GP70 enhanced MCT7-mediated taurine transport. In summary, these findings reveal that taurine is a novel substrate of MCT7 and that MCT7-mediated taurine transport might contribute to the efflux of taurine from cells.

Testosterone enhances taurine synthesis by upregulating androgen receptor and cysteine sulfinic acid decarboxylase expressions in male mouse liver.

Taurine is an end-product of cysteine metabolism, whereas cysteine dioxygenase (CDO) and cysteine sulfinate decarboxylase (CSAD) are key enzymes regulating taurine synthesis. Sex steroids, including estrogens and androgens, are associated with liver physiopathological processes; however, we still do not know whether taurine and sex steroids interact in regulating liver physiology and hepatic diseases, and whether there are sex differences, although our recent study shows that the estrogen is involved in regulating taurine synthesis in mouse liver. The present study was thus proposed to identify whether 17-ß-estradiol and testosterone (T) play their roles by regulating CDO and CSAD expression and taurine synthesis in male mouse liver. Our results demonstrated that testosterone did not have a significant influence on CDO expression but significantly enhanced CSAD, androgen receptor (AR) expressions, and taurine levels in mouse liver, cultured hepatocytes, and HepG2 cells, whereas these effects were abrogated by AR antagonist flutamide. Furthermore, our results showed that testosterone increased CSAD-promoter-luciferase activity through the direct interaction of the AR DNA binding domain with the CSAD promoter. These findings first demonstrate that testosterone acts as an important factor to regulate sulfur amino acid metabolism and taurine synthesis through AR/CSAD signaling pathway. In addition, the in vivo and in vitro experiments showed that 17-ß-estradiol has no significant effects on liver CSAD expression and taurine synthesis in male mice and suggest that the effects of sex steroids on the taurine synthesis in mouse liver have sex differences. These results are crucial for understanding the physiological functions of taurine/androgen and their interacting mechanisms in the liver.NEW & NOTEWORTHY This study demonstrates that testosterone functions to enhance taurine synthesis by interacting with androgen receptor and binding to cysteine sulfinate decarboxylase (CSAD) promoter zone. Whereas estrogen has no significant effects either on liver CSAD expression or taurine synthesis in male mice and suggests that the effects of sex steroids on taurine synthesis in the liver have gender differences. These new findings are the potential for establishing effective protective and therapeutic strategies for liver diseases.

Taurine enhances the antitumor efficacy of PD-1 antibody by boosting CD8+ T cell function.

The functional state of CD8+ T cells determines the therapeutic efficacy of PD-1 blockade antibodies in tumors. Amino acids are key nutrients for maintaining T cell antitumor immunity. In this study, we used samples from lung cancer patients treated with PD-1 blockade antibodies to assay the amino acids in their serum by mass spectrometry. We found that lung cancer patients with high serum taurine levels generally responded to PD-1 blockade antibody therapy, in parallel with the secretion of high levels of cytotoxic cytokines (IFN-γ and TNF-α). CD8+ T cells cultured with exogenous taurine exhibited decreased apoptosis, enhanced proliferation, and increased secretion of cytotoxic cytokines. High SLC6A6 expression in CD8+ T cells was positively associated with an effector T cell signature. SLC6A6 knockdown limited the function and proliferation of CD8+ T cells. RNA sequencing revealed that SLC6A6 knockdown altered the calcium signaling pathway, oxidative phosphorylation, and T cell receptor signaling in CD8+ T cells. Furthermore, taurine enhanced T cell proliferation and function in vitro by stimulation of PLCγ1-mediated calcium and MAPK signaling. Taurine plus immune checkpoint blockade antibody significantly attenuated tumor growth and markedly improved the function and proliferation of CD8+ T cells in a mouse tumor model. Thus, our findings indicate that taurine is an important driver for improving CD8+ T cell immune responses and could serve as a potential therapeutic agent for cancer patients.

The Pulse of It: Dietary Inclusion of Up to 45% Whole Pulse Ingredients with Chicken Meal and Pea Starch in a Complete and Balanced Diet Does Not Affect Cardiac Function, Fasted Sulfur Amino Acid Status, or Other Gross Measures of Health in Adult Dogs.

BACKGROUND: Pulses are an attractive alternative protein source for all mammals; however, recent reports suggest that these ingredients may be related to developing dilated cardiomyopathy in dogs. OBJECTIVES: The primary objective of this study was to quantify the effects of dietary pulse intake by adult dogs on cardiac function using echocardiographic measurements and cardiac biomarkers N-terminal pro-B-type natriuretic peptide and cardiac troponin I (cTnI). Second, to investigate the effects of pulse consumption on plasma sulfur amino acid (SAA) concentrations as pulses are generally low in SAA and may limit taurine synthesis. Last, to assess the general safety and efficacy of feeding pulse-containing diets on canine body composition and hematological and biochemical indices. METHODS: Twenty-eight privately-owned domestic Siberian Huskies (13 females; 4 intact, and 15 males; 6 intact) with a mean age of 5.3 ± 2.8 y (± SD) were randomly assigned to 1 of 4 dietary treatments (n = 7/treatment), with equal micronutrient supplementation and increasing whole pulse ingredient inclusion (0%, 15%, 30%, and 45%) with pea starch used to balance protein and energy. RESULTS: After 20 wks of feeding, there were no differences (P > 0.05) in echocardiographic parameters, N-terminal pro-B-type natriuretic peptide, and cTnI concentrations among treatments or across time within treatment (P > 0.05), indicating no differences in cardiac function among treatments. Concentrations of cTnI remained below the safe upper limit of 0.2 ng/mL for all dogs. Plasma SAA status, body composition, and hematological and biochemical indices were similar among treatments and over time (P > 0.05). CONCLUSIONS: The results from this study suggest that increasing the inclusion of pulses up to 45% with the removal of grains and equal micronutrient supplementation does not impact cardiac function concurrent with dilated cardiomyopathy, body composition, or SAA status and is safe for healthy adult dogs to consume when fed for 20 wks.

Taurine Alleviates Chronic Social Defeat Stress-Induced Depression by Protecting Cortical Neurons from Dendritic Spine Loss.

Abnormal amino acid metabolism in neural cells is involved in the occurrence and development of major depressive disorder. Taurine is an important amino acid required for brain development. Here, microdialysis combined with metabonomic analysis revealed that the level of taurine in the extracellular fluid of the cerebral medial prefrontal cortex (mPFC) was significantly reduced in mice with chronic social defeat stress (CSDS)-induced depression. Therefore, taurine supplementation may be usable an intervention for depression. We found that taurine supplementation effectively rescued immobility time during a tail suspension assay and improved social avoidance behaviors in CSDS mice. Moreover, taurine treatment protected CSDS mice from impairments in dendritic complexity, spine density, and the proportions of different types of spines. The expression of N-methyl D-aspartate receptor subunit 2A, an important synaptic receptor, was largely restored in the mPFC of these mice after taurine supplementation. These results demonstrated that taurine exerted an antidepressive effect by protecting cortical neurons from dendritic spine loss and synaptic protein deficits.

Interaction of exercise training with taurine attenuates infarct size and cardiac dysfunction via Akt-Foxo3a-Caspase-8 signaling pathway.

This research aimed to investigate the synergistic protective effect of exercise training and taurine on Akt-Foxo3a-Caspase-8 signaling related to infarct size and cardiac dysfunction. Therefore, 25 male Wistar rats with MI were divided into five groups: sham (Sh), control-MI(C-MI), exercise training-MI(Exe-MI), taurine supplementation-MI(Supp-MI), and exercise training + taurine-MI(Exe + Supp-MI). The taurine groups were given a 200 mg/kg/day dose of taurine by drinking water. Exercise training was conducted for 8 weeks (5 days/week), each session alternated 2 min with 25-30% VO2peak and 4 min with 55-60% VO2peak for 10 alternations. Then, the left ventricle tissue samples were taken from all groups. Exercise training and taurine activated Akt and decreased Foxo3a. Expression of the caspase-8 gene was increased in cardiac necrosis after MI, While, after 12 weeks of intervention decreased. Results exhibited that exercise training combined with taurine has a greater effect than either alone on activating the Akt-Foxo3a-caspase signaling pathway (P < 0.001). MI-induced myocardial injury leads to increase collagen deposition (P < 0.001) and infarct size and results in cardiac dysfunction via reduced stroke volume, ejection fraction, and fractional shortening (P < 0.001). Exercise training and taurine improved cardiac functional parameters (SV, EF, FS) and infarct size (P < 0.001) after 8 weeks of intervention in rats with MI. Also, the interaction of exercise training and taurine has a greater effect than alone on these variables. Interaction of exercise training with taurine supplementation induces a general amelioration of the cardiac histopathological profiles and improves cardiac remodeling via activating Akt-Foxo3a-Caspase-8 signaling with protective effects against MI.

The renoprotective effects of taurine against diabetic nephropathy via the p38 MAPK and TGF-ß/Smad2/3 signaling pathways.

Diabetic nephropathy (DN), a severe diabetes complication, causes kidney morphological and structural changes due to extracellular matrix accumulation. This accumulation is caused mainly by oxidative stress. Semi-essential amino acid derivative taurine has powerful antioxidant and antifibrotic effects. The aim of this study was to investigate the renoprotective effects of taurine through its possible roles in oxidative stress, extracellular matrix proteins, and the signaling pathways associated with the accumulation of extracellular matrix proteins in DN rats. 29 Wistar albino rats were randomly separated into control, taurine, diabetes, and diabetes + taurine groups. Diabetes animals were injected 45 mg/kg streptozosine. Taurine is given by adding to drinking water as 1% (w/v). Urine, serum, and kidney tissue were collected from rats for biochemical and histological analysis after 12 weeks. According to the studies, taurine significantly reduces the levels of malondialdehyde (MDA), total oxidant status (TOS), and protein expression of NADPH oxidase 4 (NOX4) that increase in diabetic kidney tissue. Also, decreased superoxide dismutase (SOD) activity levels significantly increased with taurine in diabetic rats. Moreover, increased mRNA and protein levels of fibronectin decreased with taurine. The matrix metalloproteinase (MMP)-2 and MMP-9 activities and their mRNA levels increased significantly, and this increase was significantly summed with taurine. There was a decrease in mRNA expression of Extracellular matrix metalloproteinase inducer (EMMPRIN). Taurine significantly increased this decrease. Diabetes increased mRNA expressions of transforming growth factor (TGF)-ß and Smad2/3. Taurine significantly reduced this induction. TGF-ß protein expression, p38, and Smad2/3 activations were also inhibited, but taurine was suppressed significantly. All these findings indicate that taurine may be an effective practical strategy to prevent renal diabetic injury.