Alleviation of taurine on liver injury of type 2 diabetic rats by improving antioxidant and anti-inflammatory capacity.

Type 2 diabetes mellitus (T2DM) is a serious metabolic disease characterized by insulin resistance and reduced insulin production, which causes abnormally elevated blood glucose. It has been reported that T2DM can enhance oxidative stress and inflammatory responses, and stimulate a variety of complications including liver injury. Studies have shown that taurine has antioxidant and anti-inflammatory effects that can not only ameliorate diabetes but also alleviate liver injury caused by various diseases. However, its effect on liver injury in T2DM is not clear. In our study, a high-fat diet and intraperitoneal injection of streptozotocin (STZ) was used to induce liver injury in T2DM rats, and taurine was given as a treatment. Through the use of HE staining on paraffin sections, ELISA, and qRT-PCR, the effects of taurine on liver pathological alterations, antioxidant capacity, and inflammatory response were investigated. We found that: hepatic transaminase levels of rats were reduced significantly following taurine administration; histopathological observations revealed that the morphology of rat hepatocytes was close to normal, and the number of inflammatory cells around liver vessels was significantly reduced; antioxidant-related indicators were significantly increased, including SOD, CAT, GSH-Px and T-AOC, while related factors of the Nrf2 signalling pathway and its downstream HO-1, NQO1 and γ-GCS were significantly increased; the expression of the JAK2-STAT1 signalling pathway, TLR4/NF-κB signalling pathway and NLRP3 inflammatory vesicle-related factors were significantly reduced. Our results suggest taurine can alleviate T2DM-induced liver injury by improving the antioxidant capacity of the liver and inhibiting macrophage M1-type polarization and the inflammatory response mediated thereby.

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.

Association of taurine intake with changes in physical fitness among community-dwelling middle-aged and older Japanese adults: an 8-year longitudinal study.

Introduction: Taurine has diverse valuable biological functions, including antioxidant activity and regulation of osmotic pressure. Maintaining physical fitness from middle age is important for healthy life expectancy. Although taurine administration improves muscle endurance and strength, its role in maintenance remains unclear. We aimed to clarify the longitudinal taurine intake association with fitness changes. Methods: Participants comprised men and women aged ≥40 years who participated in the third (2002-2004; Baseline) and seventh (2010-2012; Follow-up) waves of the National Institute for Longevity Sciences-Longitudinal Study of Aging (NILS-LSA) and completed a 3-day dietary weights recording survey at baseline. A table of taurine content was prepared for 751 foods (including five food groups: Seaweed; Fish and shellfish; Meat; Eggs; and Milk and dairy products) from the Standard Tables of Food Composition in Japan (1,878 foods) 2010. Four physical fitness items (knee extension muscle strength, sit-and-reach, one-leg standing with eyes closed, and maximum walking speed) were measured at baseline and follow-up. We analyzed the association of taurine intake with physical fitness change, employing a general linear model (GLM) and trend tests for baseline taurine intake and follow-up fitness change. Adjustments included baseline variables: sex, age, height, weight, educational level, self-rated health, smoking status, depressive symptoms, and clinical history. Results: The estimated average daily taurine intake (standard deviation) was 207.5 (145.6) mg/day at the baseline. When examining the association with the four physical fitness parameters, higher taurine intake positively increased the change in knee extension muscle strength (T1; 0.1, T2; 0.8, T3; 1.1 (kgf) GLM, p < 0.05; p for trend <0.05) and reduced the decline in knee extension muscle strength in the subgroup analysis of participants aged ≥65 years (T1: -1.9, T2: -1.7, T3: -0.4 kgf; GLM p < 0.05, p for trend <0.05). No relationship was found between taurine intake and the remaining three fitness factors. Conclusion: Estimation of taurine intake showed that dietary taurine intake potentially contributes to the maintenance of knee extension muscle strength over 8 years among Japanese community-dwelling middle-aged and older individuals. This is the first study to investigate the association of dietary taurine intake with muscle strength.

Taurine dynamics in serum during the oestrous cycle in buffaloes.

Estrus identification is one of the common issues in buffaloes because of their short estrus duration and silent estrus problem. Hence, specific biomarkers facilitating in identifying the estrus stage would be helpful to buffalo farmers and researchers. In our previous studies, taurine, a non-protein amino acid that helps in the secretion of reproductive hormones such as GnRH, was found to be associated with postpartum anestrus in buffaloes. Therefore, the present study was conducted to explore the level of taurine in serum during different stages of the oestrous cycle in healthy cyclic buffaloes. Blood samples were collected from healthy cyclic buffaloes (n = 4), and taurine was estimated at the estrus (0th day), proestrus (-2nd day), metestrus (3rd day) and diestrus (+10th day) stages using TLC method. The days of the oestrous cycle were determined by ultrasonography and observation of behavioural signs by trained professionals. The results revealed that taurine was consistently present in the serum. However, the highest concentration of taurine was observed at the proestrus (0.20 ± 0.03 mg/mL) stage, which was greater (p < .05) than metestrus (0.10 ± 0.05 mg/mL) and diestrus (0.13 ± 0.03 mg/mL) stages, but comparable with the estrus stage. These results were also validated in the simulated population datasets of population size 6 to 10,000. Further, ROC curve analysis for the large simulated population indicated the efficiency of taurine to distinguish proestrus from metestrus and diestrus stages at a lower cutoff value of <0.1643 mg/mL with 60% sensitivity and specificity. Therefore, the present study concludes that serum taurine concentration could help in detecting proestrus stage of buffalo estrous cycle.

Respiratory Responses to Single Oral Administration of Taurine in Sprague-Dawley Rats.

Taurine is a nonessential amino acid that has been increasingly consumed due to its various beneficial biological effects. Excessive taurine intake has been linked to the positive regulation of inflammatory responses and endoplasmic reticulum stress through the modulation of intracellular calcium levels. However, research on the potential adverse effects of taurine consumption on the respiratory system is limited. To address this, we investigated the respiratory responses of 6-week-old male Sprague-Dawley rats to taurine administered orally at 0, 100, 200, and 400 mg/kg. Respiratory rate, tidal volume, and minute volume were monitored in accordance with the International Council for Harmonization of Technical Requirements for Pharmaceuticals for Human Use (ICH) Harmonized Tripartite Guideline S7A for Safety Pharmacology Studies for Human Pharmaceuticals. We found that taurine administration did not significantly alter respiratory rate or tidal volume; however, a significant increase in minute volume was observed 6 h after administration of 200 mg/kg taurine.

The effect of 8-day oral taurine supplementation on thermoregulation during low-intensity exercise at fixed heat production in hot conditions of incremental humidity.

PURPOSE: To determine the effect of taurine supplementation on sweating and core temperature responses, including the transition from compensable to uncompensable heat stress, during prolonged low-intensity exercise of a fixed-heat production (~ 200W/m2) in hot conditions (37.5 °C), at both fixed and incremental vapour-pressure. METHODS: Fifteen females (n = 3) and males (n = 12; 27 ± 5 years, 78 ± 9 kg, V ˙ O2max 50.3 ± 7.8 mL/kg/min), completed a treadmill walking protocol (~ 200W/m2 heat production [Hprod]) in the heat (37.5 ± 0.1 °C) at fixed-(16-mmHg) and ramped-humidity (∆1.5-mmHg/5-min) following 1 week of oral taurine supplementation (50 mg/kg/bm) or placebo, in a double-blind, randomised, cross-over design. Participants were assessed for whole-body sweat loss (WBSL), local sweat rate (LSR), sweat gland activation (SGA), core temperature (Tcore), breakpoint of compensability (Pcrit) and calorimetric heat transfer components. Plasma volume and plasma taurine concentrations were established through pre- and post-trial blood samples. RESULTS: Taurine supplementation increased WBSL by 26.6% and 5.1% (p = 0.035), LSR by 15.5% and 7.8% (p = 0.013), SGA (1 × 1 cm) by 32.2% and 29.9% (p < 0.001) and SGA (3 × 3 cm) by 22.1% and 17.1% (p = 0.015) during the fixed- and ramped-humidity exercise periods, respectively. Evaporative heat loss was enhanced by 27% (p = 0.010), heat-storage reduced by 72% (p = 0.024) and Pcrit was greater in taurine vs placebo (25.0-mmHg vs 21.7-mmHg; p = 0.002). CONCLUSION: Taurine supplementation increased sweating responses during fixed Hprod in hot conditions, prior to substantial heat strain and before the breakpoint of compensability, demonstrating improved thermoregulatory capacity. The enhanced evaporative cooling and reduced heat-storage delayed the subsequent upward inflection in Tcore-represented by a greater Pcrit-and offers a potential dietary supplementation strategy to support thermoregulation.

Folic Acid and Taurine Alleviate the Impairment of Redox Status, Immunity, Rumen Microbial Composition and Fermentation of Lambs under Heat Stress.

The aim of this study was to investigate if the supplementation of folic acid and taurine can relieve the adverse effects of different levels of heat stress (HS) on growth performance, physiological indices, antioxidative capacity, immunity, rumen fermentation and microbiota. A total of 24 Dorper × Hu crossbred lambs (27.51 ± 0.96 kg) were divided into four groups: control group (C, 25 °C), moderate HS group (MHS, 35 °C), severe HS group (SHS, 40 °C), and the treatment group, under severe HS (RHS, 40 °C, 4 and 40 mg/kg BW/d coated folic acid and taurine, respectively). Results showed that, compared with Group C, HS significantly decreased the ADG of lambs (p < 0.05), and the ADG in the RHS group was markedly higher than in the MHS and SHS group (p < 0.05). HS had significant detrimental effects on physiological indices, antioxidative indices and immune status on the 4th day (p < 0.05). The physiological indices, such as RR and ST, increased significantly (p < 0.05) with the HS level and were significantly decreased in the RHS group, compared to the SHS group (p < 0.05). HS induced the significant increase of MDA, TNF-α, and IL-ß, and the decrease of T-AOC, SOD, GPx, IL-10, IL-13, IgA, IgG, and IgM (p < 0.05). However, there was a significant improvement in these indices after the supplementation of folic acid and taurine under HS. Moreover, there were a significant increase in Quinella and Succinivibrio, and an evident decrease of the genera Rikenellaceae_RC9_gut_group and Asteroleplasma under HS (p < 0.05). The LEfSe analysis showed that the genera Butyrivibrio, Eubacterium_ventriosum_group, and f_Bifidobacteriaceae were enriched in the MHS, SHS and RHS groups, respectively. Correlated analysis indicated that the genus Rikenellaceae_RC9_gut_group was positively associated with MDA, while it was negatively involved in IL-10, IgA, IgM, and SOD (p < 0.05); The genus Anaeroplasma was positively associated with the propionate and valerate, while the genus Succinivibrio was negatively involved in TNF-α (p < 0.05). In conclusion, folic acid and taurine may alleviate the adverse effects of HS on antioxidant capacity, immunomodulation, and rumen fermentation of lambs by inducing changes in the microbiome that improve animal growth performance.

Short Communication: Taurine Long-Term Treatment Prevents the Development of Cardiac Hypertrophy, and Premature Death in Hereditary Cardiomyopathy of the Hamster Is Sex-Independent.

Recently, we reported that during the hypertrophic phase (230 days old) of hereditary cardiomyopathy of the hamster (HCMH), short-term treatment (20 days) with 250 mg/kg/day of taurine prevents the development of hypertrophy in males but not in females. However, the mortality rate in non-treated animals was higher in females than in males. To verify whether the sex-dependency effect of taurine is due to the difference in the disease's progression, we treated the 230-day-old animals for a longer time period of 122 days. Our results showed that long-term treatment with low and high concentrations of taurine significantly prevents cardiac hypertrophy and early death in HCMH males (p < 0.0001 and p < 0.05, respectively) and females (p < 0.01 and p < 0.0001, respectively). Our results demonstrate that the reported sex dependency of short-term treatments with taurine is due to a higher degree of heart remodeling in females when compared to males and not to sex dependency. In addition, sex-dependency studies should consider the differences between the male and female progression of the disease. Thus, long-term taurine therapies are recommended to prevent remodeling and early death in hereditary cardiomyopathy.

Taurine ameliorates sensorimotor function by inhibiting apoptosis and activating A2 astrocytes in mice after subarachnoid hemorrhage.

Subarachnoid hemorrhage (SAH) is a form of severe acute stroke with very high mortality and disability rates. Early brain injury (EBI) and delayed cerebral ischemia (DCI) contribute to the poor prognosis of patients with SAH. Currently, some researchers have started to focus on changes in amino acid metabolism that occur in brain tissues after SAH. Taurine is a sulfur-containing amino acid that is semi-essential in animals, and it plays important roles in various processes, such as neurodevelopment, osmotic pressure regulation, and membrane stabilization. In acute stroke, such as cerebral hemorrhage, taurine plays a neuroprotective role. However, the role of taurine after subarachnoid hemorrhage has rarely been reported. In the present study, we established a mouse model of SAH. We found that taurine administration effectively improved the sensorimotor function of these mice. In addition, taurine treatment alleviated sensorimotor neuron damage and reduced the proportion of apoptotic cells. Furthermore, taurine treatment enhanced the polarization of astrocytes toward the neuroprotective phenotype while inhibiting their polarization toward the neurotoxic phenotype. This study is the first to reveal the relationship between taurine and astrocyte polarization and may provide a new strategy for SAH research and clinical treatment.

Taurine amino acid supplementation impacts performance, blood hematology, oxidative stress, and jejunum morphology in broiler chickens.

Excess levels of free radicals cause oxidative damage to cells. Taurine is a rare amino acid with antioxidant effects whose dietary deficiency increases oxidative damage to the cell membrane. To investigate the effects of dietary taurine supplementation on performance, blood hematology, oxidative stress, and jejunum morphology in broilers, 300 broilers (Ras 308, 1D of age) were randomly allocated into 4 groups with 5 replicates of 15 birds. The experimental treatments included basic diet (control treatment) and basic diet with 1, 3, and 6 g/kg taurine amino acid. During 1 to 45 days, the inclusion of taurine supplementation in diets improved the body weight gain (BWG), feed consumption (FC), and feed conversion ratio (FCR) of broilers (P < 0.05). In CBC tests, the experimental treatments were significantly different concerning the red blood cell (RBC) count, the average hemoglobin in the cell, the RBC width in the curve, and the hematocrit (P < 0.05). Despite the significance of oxidative stress among the treatments, the control and fourth treatments showed the highest and the lowest oxidative stress, respectively (P < 0.05). Also, in jejunum morphology, the fourth treatment showed the best performance in terms of villus length and width and the villus length to crypt depth (V/C) ratio (P < 0.05). Overall, 6 g/kg taurine addition to the diet reduced oxidative stress and positive features in the jejunum morphology while improving the functional traits of broilers.

Multi-omics and chemical profiling approaches to understand the material foundation and pharmacological mechanism of Sophorae Tonkinensis Radix et Rhizome-induced liver injury in mice.

ETHNOPHARMACOLOGICAL RELEVANCE: Sophorae tonkinensis Radix et Rhizoma (STR) is an extensively applied traditional Chinese medicine (TCM) in southwest China. However, its clinical application is relatively limited due to its hepatotoxicity effects. AIM OF THE STUDY: To understand the material foundation and liver injury mechanism of STR. MATERIALS AND METHODS: Chemical compositions in STR and its prototypes in mice were profiled by ultra-performance liquid chromatography coupled quadrupole-time of flight mass spectrometry (UPLC-Q/TOF MS). STR-induced liver injury (SILI) was comprehensively evaluated by STR-treated mice mode. The histopathologic and biochemical analyses were performed to evaluate liver injury levels. Subsequently, network pharmacology and multi-omics were used to analyze the potential mechanism of SILI in vivo. And the target genes were further verified by western blot. RESULTS: A total of 152 compounds were identified or tentatively characterized in STR, including 29 alkaloids, 21 organic acids, 75 flavonoids, 1 quinone, and 26 other types. Among them, 19 components were presented in STR-medicated serum. The histopathologic and biochemical analysis revealed that hepatic injury occurred after 4 weeks of intragastric administration of STR. Network pharmacology analysis revealed that IL6, TNF, STAT3, etc. were the main core targets, and the bile secretion might play a key role in SILI. The metabolic pathways such as taurine and hypotaurine metabolism, purine metabolism, and vitamin B6 metabolism were identified in the STR exposed groups. Among them, taurine, hypotaurine, hypoxanthine, pyridoxal, and 4-pyridoxate were selected based on their high impact value and potential biological function in the process of liver injury post STR treatment. CONCLUSIONS: The mechanism and material foundation of SILI were revealed and profiled by a multi-omics strategy combined with network pharmacology and chemical profiling. Meanwhile, new insights were taken into understand the pathological mechanism of SILI.

Electrochemical Behavior of Janus Kinase Inhibitor Ruxolitinib at a Taurine-Electropolymerized Carbon Paste Electrode: Insights into Sensing Mechanisms.

Ruxolitinib (RXL) is a Janus kinase inhibitor used for treating intermediate- or high-risk myelofibrosis. This study presents an electrode modified with electrochemically polymerized taurine on a carbon paste electrode via cyclic voltammetry (CV). The surface characterization of the poly(taurine)-CP electrode was evaluated by using electrochemical (electrochemical impedance spectroscopy─EIS, CV), morphological (scanning electron microscope─SEM), and spectroscopic (Fourier-transform infrared spectroscopy─FT-IR) techniques. Under optimized conditions, RXL exhibited good linearity within the 0.01-1.0 µM concentration range, with a limit of detection (LOD) of 0.005 µM. The proposed electrochemical sensor demonstrated excellent selectivity, accuracy, precision, and repeatability. Furthermore, it effectively detected RXL in human urine and pharmaceutical samples.

Polymorphisms in the cysteine dioxygenase gene and their association with taurine content in the Pacific oyster Crassostrea gigas.

The Pacific oyster Crassostrea gigas is rich in taurine, which is crucial for its adaptation to the fluctuating intertidal environment and presents significant potential in improving taurine nutrition and boosting immunity in humans. Cysteine dioxygenase (CDO) is a key enzyme involved in the initial step of taurine biosynthesis and plays a crucial role in regulating taurine content in the body. In the present study, polymorphisms of CDO gene in C. gigas (CgCDO) and their association with taurine content were evaluated in 198 individuals. A total of 24 single nucleotide polymorphism (SNP) loci were identified in the exonic region of CgCDO gene by direct sequencing. Among these SNPs, c.279G>A and c.287C>A were found to be significantly associated with taurine content, with the GG and AA genotype at the two loci exhibiting enhanced taurine accumulation (p < 0.05). Haplotype analysis revealed that the 279GG/287AA haplotype had the highest taurine content of 29.24 mg/g, while the 279AA/287CC haplotype showed the lowest taurine content of 21.19 mg/g. These results indicated that the SNPs of CgCDO gene could influence the taurine content in C. gigas and have potential applications in the selective breeding of high-taurine varieties.

Taurine activates the AKT-mTOR axis to restore muscle mass and contractile strength in human 3D in vitro models of steroid myopathy.

Steroid myopathy is a clinically challenging condition exacerbated by prolonged corticosteroid use or adrenal tumors. In this study, we engineered a functional three-dimensional (3D) in vitro skeletal muscle model to investigate steroid myopathy. By subjecting our bioengineered muscle tissues to dexamethasone treatment, we reproduced the molecular and functional aspects of this disease. Dexamethasone caused a substantial reduction in muscle force, myotube diameter and induced fatigue. We observed nuclear translocation of the glucocorticoid receptor (GCR) and activation of the ubiquitin-proteasome system within our model, suggesting their coordinated role in muscle atrophy. We then examined the therapeutic potential of taurine in our 3D model for steroid myopathy. Our findings revealed an upregulation of phosphorylated AKT by taurine, effectively countering the hyperactivation of the ubiquitin-proteasomal pathway. Importantly, we demonstrate that discontinuing corticosteroid treatment was insufficient to restore muscle mass and function. Taurine treatment, when administered concurrently with corticosteroids, notably enhanced contractile strength and protein turnover by upregulating the AKT-mTOR axis. Our model not only identifies a promising therapeutic target, but also suggests combinatorial treatment that may benefit individuals undergoing corticosteroid treatment or those diagnosed with adrenal tumors.

Roles of Nutrients in the Brain Development, Cognitive Function, and Mood of Dogs and Cats.

The brain is the central commander of all physical activities and the expression of emotions in animals. Its development and cognitive health critically depend on the neural network that consists of neurons, glial cells (namely, non-neuronal cells), and neurotransmitters (communicators between neurons). The latter include proteinogenic amino acids (e.g., L-glutamate, L-aspartate, and glycine) and their metabolites [e.g., γ-aminobutyrate, D-aspartate, D-serine, nitric oxide, carbon monoxide, hydrogen sulfide, and monoamines (e.g., dopamine, norepinephrine, epinephrine, and serotonin)]. In addition, some non-neurotransmitter metabolites of amino acids, such as taurine, creatine, and carnosine, also play important roles in brain development, cognitive health, behavior, and mood of dogs and cats. Much evidence shows that cats require dietary ω3 (α-linolenic acid, eicosapentaenoic acid, and docosahexaenoic acid) and ω6 (linoleic acid and arachidonic acid) polyunsaturated fatty acids for the development of the central nervous system. As an essential component of membranes of neurons and glial cells, cholesterol is also crucial for cognitive development and function. In addition, vitamins and minerals are required for the metabolism of AAs, lipids, and glucose in the nervous system, and also act as antioxidants. Thus, inadequate nutrition will lead to mood disorders. Some amino acids (e.g., arginine, glycine, methionine, serine, taurine, tryptophan, and tyrosine) can help to alleviate behavioral and mood disorders (e.g., depression, anxiety and aggression). As abundant providers of all these functional amino acids and lipids, animal-sourced foods (e.g., liver, intestinal mucosa, and meat) play important roles in brain development, cognitive function, and mood of dogs and cats. This may explain, in part, why dogs and cats prefer to eat visceral organs of their prey. Adequate provision of nutrients in all phases of the life cycle (pregnancy, lactation, postnatal growth, and adulthood) is essential for optimizing neurological health, while preventing cognitive dysfunction and abnormal behavior.

GALNT2 expression is associated with glucose control and serum metabolites in patients with type 2 diabetes.

AIMS: Aim of this study was to investigate in type 2 diabetes whether expression level of GALNT2, a positive modulator of insulin sensitivity, is associated with a metabolic signature. METHODS: Five different metabolite families, including acylcarnitines, aminoacids, biogenic amines, phospholipids and sphingolipids were investigated in fasting serum of 70 patients with type 2 diabetes, by targeted metabolomics. GALNT2 expression levels were measured in peripheral white blood cells by RT-PCR. The association between GALNT2 expression and serum metabolites was assessed using false discovery rate followed by stepwise selection and, finally, multivariate model including several clinical parameters as confounders. The association between GALNT2 expression and the same clinical parameters was also investigated. RESULTS: GALNT2 expression was independently correlated with HbA1c levels (P value = 0.0052), a finding that is the likely consequence of the role of GALNT2 on insulin sensitivity. GALNT2 expression was also independently associated with serum levels of the aminoacid glycine (P value = 0.014) and two biogenic amines phenylethylamine (P value = 0.0065) and taurine (P value = 0.0011). The association of GALNT2 expression with HbA1c was not mediated by these three metabolites. CONCLUSIONS: Our data indicate that in type 2 diabetes the expression of GALNT2 is associated with several serum metabolites. This association needs to be further investigated to understand in depth its role in mediating the effect of GALNT2 on insulin sensitivity, glucose control and other clinical features in people with diabetes.

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 Activates SIRT1/AMPK/FOXO1 Signaling Pathways to Favorably Regulate Lipid Metabolism in C57BL6 Obese Mice.

SCOPE: The identification of novel therapeutic agents capable of modulating lipid metabolism holds a promising potential in combating obesity and its associated complications. This study is conducted to evaluate the lipid lowering effect of dietary taurine administration on high-fat fed C57BL6 mice and to study the mechanism by which taurine impacts lipid metabolism. METHODS AND RESULTS: C57BL6 mice are grouped into four (n = 6): i) normal diet (ND), ii) a high-fat diet (HFD), iii) HFD + orlistat (STD), iv) HFD + taurine (TAU) group for 12 weeks. The results show that taurine administration for 12 weeks reduces high fat-induced weight gain, and liver weight when compared with HFD fed mice. It also improves serum biochemical parameters like total cholesterol and triglycerides. Sirtuin 1 (SIRT1) activity, Nicotinamide adenine dinucleotide (NAD+) levels, SIRT1 mRNA, and protein expression are increased in HFD + TAU diet group as compared to HFD group. Taurine treatment suppresses the expression of lipogenic genes (sterol regulatory element binding protein 1c [SREBP1c], fatty acid synthase [FAS], Peroxisome proliferator-activated receptor gamma [PPARγ]) and increases the expression of ß-oxidation (peroxisome proliferator-activated receptor alpha [PPARα], liver x receptor beta [LXRß], peroxisome proliferator-activated receptor gamma coactivator 1-alpha [PGC1α], AMP-activated protein kinase [AMPK]) and lipolytic (forkhead box protein O1 [FOXO1]) genes. Further, taurine mitigates hepatic inflammation by suppressing nuclear factor kappa B (NF-κB) gene expression and pro-inflammatory cytokine markers (IL-6, IL-1ß, and TNFα). CONCLUSION: Taurine exerts lipid lowering effects through activating SIRT1/AMPK/FOXO1 signaling pathways and regulating their downstream targets.

Evaluation of taurine and carnitine concentrations in whole blood, plasma, skeletal muscle and cardiac muscle in dogs.

Little is known about how plasma and whole blood taurine and plasma carnitine correlate to concentrations in skeletal and cardiac muscle and the effects of diet in dogs. The purpose of this study was to evaluate the correlation among plasma, skeletal and cardiac muscle carnitine and taurine and whole blood taurine and determine the effect of diet. The study protocol was approved by the Pet Food Solutions Institutional Animal Care and Use Committee. Thirty-three mixed-breed hounds and 32 beagles were evaluated at Day 0 then removed from their baseline diet and randomized to a test diet: high animal protein, grain-inclusive (HA-GI), low animal protein, grain-free (LA-GF), low animal protein, grain-inclusive (LA-GI), or high animal protein, grain-free (HA-GF). Blood was drawn every 30 days and endomyocardial (mixed breeds only) and skeletal muscle biopsies were collected at Days 0 and 180. The correlations between plasma and whole blood taurine, or plasma carnitine and skeletal and cardiac muscle concentrations were weak (p < 0.01-0.05). Mixed-breed hounds had increased (p = 0.029) whole blood taurine compared to beagles. Plasma taurine was lower with diet HA-GF, (p = 0.009) however, all diets had increased taurine from Day 0 and were, on average within the laboratory reference range. Dogs fed the HA-GI diet had increased cardiac muscle carnitine esters (p = 0.014). Increased carnitine esters were also appreciated in cardiac muscle in all diets from Day 0 to 180 (p = 0.0001). On Day 180 mixed-breed hounds had increased skeletal total carnitine (p < 0.001) compared to all time points and breeds. This study observed no correlation between plasma, whole blood, skeletal and cardiac muscle taurine concentrations but noted some effects between time, breed and diet.

Taurine induces hormesis in multiple biological models: May have transformative implications for overall societal health.

This paper represents the first integrative assessment and documentation of taurine-induced hormetic effects in the biological and biomedical areas, their dose response features, mechanistic frameworks, and possible public health, therapeutic and commercial applications. Taurine-induced hormetic effects are documented in a wide range of experimental models, cell types and for numerous biological endpoints, with most of these experimental findings being reported within the past five years. It is suggested that the concept of hormesis may have a transformative effect on taurine research and its public health and therapeutic applications.