Taurine deficiency as a driver of aging.

Aging is associated with changes in circulating levels of various molecules, some of which remain undefined. We find that concentrations of circulating taurine decline with aging in mice, monkeys, and humans. A reversal of this decline through taurine supplementation increased the health span (the period of healthy living) and life span in mice and health span in monkeys. Mechanistically, taurine reduced cellular senescence, protected against telomerase deficiency, suppressed mitochondrial dysfunction, decreased DNA damage, and attenuated inflammaging. In humans, lower taurine concentrations correlated with several age-related diseases and taurine concentrations increased after acute endurance exercise. Thus, taurine deficiency may be a driver of aging because its reversal increases health span in worms, rodents, and primates and life span in worms and rodents. Clinical trials in humans seem warranted to test whether taurine deficiency might drive aging in humans.

Taurine linked with healthy aging.

Reversing age-associated taurine loss improves mouse longevity and monkey health.

Development and validation of an analytical method for the simultaneous determination of the alcohol biomarkers ethyl glucuronide, ethyl sulfate, N-acetyltaurine, and 16:0/18:1-phosphatidylethanol in human blood.

As alcohol is the most common addictive substance worldwide, it is inevitable to advance the established research. New and more substantial analytical methods can be applied to reply to complex questions in legal or forensic contexts. Therefore, an analytical method for the simultaneous determination of four different alcohol biomarkers-ethyl glucuronide, ethyl sulfate, N-acetyltaurine, and 16:0/18:1-phosphatidylethanol-in human blood was developed, validated, and verified. Despite the different chemical properties of the analytes, a specific determination via HPLC-MS/MS was achieved using a novel type of a Phenomenex Luna® Omega Sugar column. Furthermore, all criteria for a successful validation were fulfilled according to forensic guidelines. The method proved to be linear and demonstrates selectivity and sufficient sensitivity for every biomarker. LODs obtained with this method of 2.6 ng/ml (EtG), 4.7 ng/ml (EtS), 12.5 ng/ml (NAcT), and 6.9 ng/ml (PEth) were in an acceptable range for routine applications, and the stability of all analytes over a range of 12 h is given. The verification of the new developed method was performed with authentic samples. Thus, whole blood and postmortem samples were analyzed to obtain information about the drinking behavior, which can answer complex questions regarding alcohol consumption.

The relationship between plasma taurine levels in early pregnancy and later gestational diabetes mellitus risk in Chinese pregnant women.

Taurine is a sulfur-containing amino acid that plays an important role in glucose homeostasis. However, it remains unknown whether the plasma concentration of taurine affects the risk of later gestational diabetes mellitus (GDM) development. We recruited 398 singleton-pregnancy women and followed up them during the course of pregnancy. We measured the plasma concentrations of taurine based on blood samples collected at nine-week gestation on average and obtained the data regarding both mothers and their infants from medical records. There was a significant increment in the mean value of HOMA-ß across the tertiles of plasma taurine in multiparous women rather than in primiparous women. After adjustment for confounders, an increase of plasma taurine was nominally and significantly associated with a decrease risk of GDM; moreover, women with plasma taurine concentrations in the lowest tertile and in the second tertile had a higher risk of GDM than did those with plasma taurine in the top tertile in multiparous women other than primiparous women. Plasma taurine level seems to be associated with insulin secretion in early pregnancy and be more closely associated with ß-cell function and the risk of GDM development in multiparas in comparison to primiparas.

TAT delivery of a PTEN peptide inhibitor has direct cardioprotective effects and improves outcomes in rodent models of cardiac arrest.

We have recently shown that pharmacologic inhibition of PTEN significantly increases cardiac arrest survival in a mouse model, however, this protection required pretreatment 30 min before the arrest. To improve the onset of PTEN inhibition during cardiac arrest treatment, we have designed a TAT fused cell-permeable peptide (TAT-PTEN9c) based on the C-terminal PDZ binding motif of PTEN for rapid tissue delivery and protection. Western blot analysis demonstrated that TAT-PTEN9c peptide significantly enhanced Akt activation in mouse cardiomyocytes in a concentration- and time-dependent manner. Mice were subjected to 8 min asystolic arrest followed by CPR, and 30 mice with successful CPR were then randomly assigned to receive either saline or TAT-PTEN9c treatment. Survival was significantly increased in TAT-PTEN9c-treated mice compared with that of saline control at 4 h after CPR. The treated mice had increased Akt phosphorylation at 30 min resuscitation with significantly decreased sorbitol content in heart or brain tissues and reduced release of taurine and glutamate in blood, suggesting improved glucose metabolism. In an isolated rat heart Langendorff model, direct effects of TAT-PTEN9c on cardiac function were measured for 20 min following 20 min global ischemia. Rate pressure product was reduced by >20% for both TAT vehicle and nontreatment groups following arrest. Cardiac contractile function was completely recovered with TAT-PTEN9c treatment given at the start of reperfusion. We conclude that TAT-PTEN9c enhances Akt activation and decreases glucose shunting to the polyol pathway in critical organs, thereby preventing osmotic injury and early cardiovascular collapse and death.NEW & NOTEWORTHY We have designed a cell-permeable peptide, TAT-PTEN9c, to improve cardiac arrest survival. It blocked endogenous PTEN binding to its adaptor and enhanced Akt signaling in mouse cardiomyocytes. It improved mouse survival after cardiac arrest, which is related to improved glucose metabolism and reduced glucose shunting to sorbitol in critical organs.

A plasma metabolomic signature of Leber hereditary optic neuropathy showing taurine and nicotinamide deficiencies.

Leber's hereditary optic neuropathy (LHON) is the most common disorder due to mitochondrial DNA mutations and complex I deficiency. It is characterized by an acute vision loss, generally in young adults, with a higher penetrance in males. How complex I dysfunction induces the peculiar LHON clinical presentation remains an unanswered question. To gain an insight into this question, we carried out a non-targeted metabolomic investigation using the plasma of 18 LHON patients, during the chronic phase of the disease, comparing them to 18 healthy controls. A total of 500 metabolites were screened of which 156 were accurately detected. A supervised Orthogonal Partial Least Squares-Discriminant Analysis (OPLS-DA) highlighted a robust model for disease prediction with a Q2 (cum) of 55.5%, with a reliable performance during the permutation test (cross-validation analysis of variance, P-value = 5.02284e-05) and a good prediction of a test set (P = 0.05). This model highlighted 10 metabolites with variable importance in the projection (VIP) > 0.8. Univariate analyses revealed nine discriminating metabolites, six of which were the same as those found in the Orthogonal Projections to Latent Structures Discriminant Analysis model. In total, the 13 discriminating metabolites identified underlining dietary metabolites (nicotinamide, taurine, choline, 1-methylhistidine and hippurate), mitochondrial energetic substrates (acetoacetate, glutamate and fumarate) and purine metabolism (inosine). The decreased concentration of taurine and nicotinamide (vitamin B3) suggest interesting therapeutic targets, given their neuroprotective roles that have already been demonstrated for retinal ganglion cells. Our results show a reliable predictive metabolomic signature in the plasma of LHON patients and highlighted taurine and nicotinamide deficiencies.

Glial Cell Activation and Oxidative Stress in Retinal Degeneration Induced by ß-Alanine Caused Taurine Depletion and Light Exposure.

We investigate glial cell activation and oxidative stress induced by taurine deficiency secondary to ß-alanine administration and light exposure. Two months old Sprague-Dawley rats were divided into a control group and three experimental groups that were treated with 3% ß-alanine in drinking water (taurine depleted) for two months, light exposed or both. Retinal and external thickness were measured in vivo at baseline and pre-processing with Spectral-Domain Optical Coherence Tomography (SD-OCT). Retinal cryostat cross sections were immunodetected with antibodies against various antigens to investigate microglial and macroglial cell reaction, photoreceptor outer segments, synaptic connections and oxidative stress. Taurine depletion caused a decrease in retinal thickness, shortening of photoreceptor outer segments, microglial cell activation, oxidative stress in the outer and inner nuclear layers and the ganglion cell layer and synaptic loss. These events were also observed in light exposed animals, which in addition showed photoreceptor death and macroglial cell reactivity. Light exposure under taurine depletion further increased glial cell reaction and oxidative stress. Finally, the retinal pigment epithelial cells were Fluorogold labeled and whole mounted, and we document that taurine depletion impairs their phagocytic capacity. We conclude that taurine depletion causes cell damage to various retinal layers including retinal pigment epithelial cells, photoreceptors and retinal ganglion cells, and increases the susceptibility of the photoreceptor outer segments to light damage. Thus, beta-alanine supplements should be used with caution.

New Insights into Diabetic and Vision-Threatening Retinopathy: Importance of Plasma Long Pentraxine 3 and Taurine Levels.

PURPOSE: To investigate diabetic retinopathy (DR), plasma long pentraxin-3 (PTX-3) and taurine levels, and systemic factors in patients with type 2 diabetes mellitus (DM). MATERIALS AND METHODS: Patients with type 2 DM were categorized based on the presence of DR and maculopathy. Retinal findings (retinopathy, maculopathy, flame-shaped hemorrhage, intraretinal microvascular abnormalities, neovascularization of the optic disc, neovascularization elsewhere, and soft exudate); laboratory findings (fasting blood glucose, glycosylated hemoglobin [HbA1c], Taurine, PTX-3); systolic blood pressure (SBP) and diastolic blood pressure (DBP) were analyzed. RESULTS: In this study, 39 patients with a mean age of 59.5 ± 8.1 years were included. The mean taurine level was significantly lower (p = .025) and HbA1c values were significantly higher (p = .0001) in patients with and without DR, respectively. In patients with varying severity of DR, a significant difference in the plasma taurine level was found (p = .0001). The mean PTX-3 level decreased with the severity of retinopathy; however, there was no significant difference in levels among the grading groups (p = .732). Taurine and PTX-3 levels were significantly lower in patients with maculopathy (p = .001 and p = .022, respectively) and significantly higher in patients with grade 0 maculopathy than in those with grade 1, 2, or 3 maculopathy (p = .023, p = .01, and p = .01, respectively). Patients with flame-shaped hemorrhage had significantly lower PTX-3 levels (p = .009) and higher SBP and DBP levels (p = .003, p = .023) than those without the hemorrhage. CONCLUSIONS: No significant relation between PTX-3 level and severity of DR was found. HbA1c, taurine, and PTX-3 levels in patients with vision-threatening DR symptoms were significantly different from those without these symptoms. Management of systemic blood pressure and glycemic control is mandatory in the follow-up of DR, and increasing the plasma taurine levels can prevent vision loss.

Association of taurine with ovarian follicular steroids and postpartum anestrus condition in Murrah buffaloes.

Taurine is an abundant intracellular beta-amino acid majorly synthesized in the liver and transported through plasma. In mammals, taurine was reported to be involved in various physiological functions, including the enhancement of testosterone levels, the major estradiol precursor. Therefore, we hypothesize that taurine levels are associated with ovarian follicular steroids as well as with a reproductive problem called postpartum anestrus (PPA) in dairy buffaloes. To understand the taurine levels and its possible role in buffalo ovarian follicles, a correlation was established among taurine, estradiol, and testosterone levels in the ovarian follicular fluid. For this purpose, buffalo ovaries were obtained from the slaughterhouse, and follicular fluid samples were collected from small (<4 mm), medium (4-8 mm) and large (>8 mm) follicles. Taurine and steroid levels in the follicular fluid were analyzed by TLC and ELISA, respectively. Taurine and testosterone levels were significantly (P < 0.05) higher in the follicular fluid of small and medium follicles than large follicles, whereas the estradiol levels were significantly (P < 0.001) higher in the large follicles. Thus, taurine showed a positive correlation (r = 0.75) with testosterone and a negative correlation (r = -0.77) with estradiol in buffalo follicular fluid, indicating its possible role in testosterone function during follicular development. Interestingly, significantly (P < 0.001) lower plasma taurine levels in PPA (n = 50) than normal cyclic (n = 50) buffaloes represented its association with PPA. Therefore, our present study recommends the need for future nutrition studies on taurine supplementation to PPA buffaloes.

Plasma metabolomic profiling of central serous chorioretinopathy.

Our study aimed to investigate metabolites alterations in the blood plasma of central serous chorioretinopathy (CSC) patients and to identify the key biomarkers to increase the understanding of the mechanism of CSC at the molecular level. Quantitative and targeted metabolomics using liquid chromatography tandem-mass spectrometry (LCMS, Biocrates P500) assays were performed on plasma samples from the 42 subjects(CSC patients = 30, control = 12) enrolled at the Department of Ophthalmology of People's Hospital Peking University. A total of 61 altered metabolites were distinguished between CSC patients and controls. Taurine was selected as a candidate biomarker for CSC among 6 potential metobolites: taurine, glutamic acid, sarcosine, lactic acid, glutamine and C18_1. The P values of these potential metabolites were 1.01E-06, 7.35E-08, 1.27E-24, and 1.85E-10, 1.02E-05 and 8.59E-08, and the areas under the curve for them were 0.926, 0.991, 1.000, 0.900, 0.897 and 0.841, respectively. This study is the first to identify that taurine may be a biologically relevant biomarker for CSC and to provide a novel understanding of CSC.

Effectiveness of 4-Week Oral Taurine Treatment for Muscle Cramps in Patients with Liver Cirrhosis: A Single-Arm Pilot Study.

PURPOSE: Painful muscle cramps are a common complication in liver cirrhosis patients, and no effective treatment is available. This pilot study aimed to evaluate whether taurine supplementation improves muscle cramps in Korean cirrhotic patients. MATERIALS AND METHODS: Ten cirrhotic patients who experienced muscle cramps one or more times/week were enrolled in this prospective single-arm study and administered with an oral taurine solution (1 g/50 mL) thrice a day for 4 weeks. Taurine was discontinued for the subsequent 4 weeks. The frequency and intensity of muscle cramps were evaluated using a questionnaire at weeks 0, 2, 4, 6, and 8 after the start of treatment. RESULTS: At baseline, the median frequency of muscle cramps was six times/week, and all patients had severe pain. Muscle cramp scores (frequency×intensity) decreased in seven patients by weeks 4 and 8 after treatment initiation. Compared to baseline muscle cramp scores [median 21, interquartile range (IQR): 8-84], median muscle cramp scores were lower at week 4 (6.5, IQR: 3-12, p=0.126) and week 8 (5, IQR: 1.5-56, p=0.066). All five patients whose baseline plasma taurine levels were below the normal limit showed increased taurine levels at week 4; 60% of them experienced improvements in their muscle cramps. Of the five patients with normal or higher taurine levels, 80% experienced an improvement in symptoms at week 4. The safety and tolerability of the 4-week taurine therapy were excellent. CONCLUSION: Oral taurine therapy for 4 weeks improved muscle cramps safely in cirrhotic patients.

Metabolomics approach revealed robust changes in amino acid and biogenic amine signatures in patients with schizophrenia in the early course of the disease.

The primary objective of this study was to evaluate how schizophrenia (SCH) spectrum disorders and applied antipsychotic (AP) treatment affect serum level of amino acids (AAs) and biogenic amines (BAs) in the early course of the disorder. We measured 21 different AAs and 10 BAs in a sample of antipsychotic (AP)-naïve first-episode psychosis (FEP) patients (n = 52) at baseline, after 0.6-year as well as after 5.1-year treatment compared to control subjects (CSs, n = 37). Serum levels of metabolites were determined with AbsoluteIDQ p180 kit using flow injection analysis tandem mass spectrometry and liquid chromatography technique. Elevated level of taurine and reduced level of proline and alpha-aminoadipic acid (alpha-AAA) were established as metabolites with significant change in AP-naïve FEP patients compared to CSs. The following 0.6-year treatment restored these alterations. However, further continuous 5.1-year AP treatment changed the metabolic profile substantially. Significantly elevated levels of asparagine, glutamine, methionine, ornithine and taurine, alongside with decreased levels of aspartate, glutamate and alpha-AAA were observed in the patient group compared to CSs. These biomolecule profile alterations provide further insights into the pathophysiology of SCH spectrum disorders and broaden our understanding of the impact of AP treatment in the early stages of the disease.

Taurine Supplementation Increases Post-Exercise Lipid Oxidation at Moderate Intensity in Fasted Healthy Males.

Based on the fact that taurine can increase lipid metabolism, the objective of the present study was to evaluate the effects of different doses of acute taurine supplementation on lipid oxidation levels in healthy young men after a single bout of fasting aerobic exercise. A double-blind, acute, and crossover study design was conducted. Seventeen men (age 24.8 ± 4.07y; BMI: 23.9 ± 2.57 kg/m²) participated in the present study. Different doses of taurine (TAU) (3 g or 6 g) or placebo were supplemented 90 minutes before a single bout of fasting aerobic exercise (on a treadmill at 60% of VO2 max). The subjects performed three trials, and each one was separated by seven days. Blood samples were collected at baseline and after the exercise protocol of each test to analyze plasma levels of glycerol and taurine. Lipid and carbohydrate oxidation were determined immediately after exercise for 15 minutes by indirect calorimetry. We observed that TAU supplementation (6 g) increased lipid oxidation (38%) and reduced the respiratory coefficient (4%) when compared to the placebo (p < 0.05). However, no differences in lipid oxidation were observed between the different doses of taurine (3 g and 6 g). For glycerol concentrations, there were no differences between trials. Six grams of TAU supplementation 90 minutes before a single bout of aerobic exercise in a fasted state was sufficient to increase the lipid oxidation post-exercise in healthy young men.

Development of plasma and whole blood taurine reference ranges and identification of dietary features associated with taurine deficiency and dilated cardiomyopathy in golden retrievers: A prospective, observational study.

INTRODUCTION: A surge in Food and Drug Administration (FDA) consumer complaints identified concerns that legume-rich, grain-free diets were associated with nutritionally-mediated dilated cardiomyopathy (DCM). Golden retrievers represent the most reported breed affected by this condition and previous studies documented the disease is responsive to dietary change and taurine supplementation. Although dietary findings across cases are compelling, prospective studies with control groups are lacking. The role of diet in developing taurine deficiency and echocardiographic changes consistent with DCM in healthy dogs is unknown. OBJECTIVES: We hypothesized that golden retrievers eating non-traditional diets are at a higher risk of having taurine deficiency and nutritionally-mediated DCM compared with those eating traditional commercial diets. We aimed to compare taurine concentrations and echocardiographic indices of systolic function between golden retrievers in each diet group and elucidate associations between diet and these variables. Additionally, we aimed to generate breed-specific reference intervals for whole blood and plasma taurine concentrations. ANIMALS: 86 golden retrievers. METHODS: Golden retrievers eating traditional or non-traditional diets were evaluated and diet history, taurine concentrations and echocardiographic data were collected. Dietary features, taurine concentrations and echocardiographic findings were compared between diet groups. Relative risks were calculated for the likelihood of echocardiographic abnormalities and taurine deficiency in each diet group. Breed-specific reference intervals were constructed for taurine concentrations in dogs from the traditional diet group. RESULTS: Golden retrievers eating non-traditional diets had significantly lower taurine concentrations and more frequent systolic dysfunction. Breed specific reference intervals are higher than previously reported across breeds. CONCLUSIONS: Non-traditional diets, which were typically grain-free and contained legumes in this study, were significantly associated with and have increased relative risk for the identification of taurine deficiency and echocardiographic abnormalities consistent with nutritionally-mediated DCM. These findings were identifiable in the absence of clinical signs and support the findings of multiple previous studies and the ongoing FDA investigation.

Two high-performance liquid chromatography-tandem mass spectrometry methods for determination of edaravone and taurine in human plasma: Application to drug-drug interaction and pharmacokinetic studies.

Two high-performance liquid chromatography-tandem mass spectrometry methods were developed and validated for the quantification of edaravone (method A) or taurine (method B) in human plasma. After protein precipitation, separations were achieved on an Ultimate XB-C8 (2.1 × 50 mm, 3.0 µm) column for edaravone and a ZORBAX SB-Aq column (2.1 × 100 mm, 3.5 µm) for taurine, respectively. The detection used electrospray ionization source via multiple reaction monitoring in positive-ion mode for edaravone and negative-ion mode for taurine, respectively. The lower limits of quantification were 10.0 ng/mL for edaravone and 3.00 µg/mL for taurine. The selectivity, accuracy, and precision of the methods were all within acceptable limits. Two methods were successfully applied to a drug-drug interaction study and a pharmacokinetic study of edaravone and taurine in healthy Chinese volunteers after intravenous infusion of single or compound injection. The results showed that co-administration of edaravone with taurine increased the Cmax and AUC0-24 of taurine in human plasma while taurine did not affect the systemic exposure of edaravone. Edaravone and taurine have the dose-dependent pharmacokinetic profiles in human.

Impaired bile acid metabolism with defectives of mitochondrial-tRNA taurine modification and bile acid taurine conjugation in the taurine depleted cats.

Taurine that conjugates with bile acid (BA) and mitochondrial-tRNA (mt-tRNA) is a conditional essential amino acid in humans, similarly to cats. To better understand the influence of acquired depletion of taurine on BA metabolism, the profiling of BAs and its intermediates, BA metabolism-enzyme expression, and taurine modified mt-tRNAs were evaluated in the taurine deficient diet-supplemented cats. In the taurine depleted cats, taurine-conjugated bile acids in bile and taurine-modified mt-tRNA in liver were significantly decreased, whereas unconjugated BA in serum was markedly increased. Impaired bile acid metabolism in the liver was induced accompanied with the decreases of mitochondrial cholesterol 27-hydroxylase expression and mitochondrial activity. Consequently, total bile acid concentration in bile was significantly decreased by the low activity of mitochondrial bile acid synthesis. These results implied that the insufficient dietary taurine intake causes impaired bile acid metabolism, and in turn, a risk for the various diseases similar to the mitochondrial diseases would be enhanced.

Metabolomics analysis identifies lysine and taurine as candidate prognostic biomarkers for AML-M2 patients.

There is an ongoing search for potential biomarkers for acute myeloid leukemia (AML) patients using metabolic analysis. However, only few studies to date have focused on bone marrow samples or a specific subtype of AML. In the present study, we used gas chromatography time-of-flight mass spectrometry of plasma and bone marrow supernatants to compare the metabolic characteristics of patients with AML with maturation (AML-M2). This approach identified significantly altered metabolites. We next performed pathway analysis and determined relative mRNA expression by qRT-PCR. Our results show that lysine, methionine and serine were significantly decreased in AML-M2 patients compared with healthy control. Moreover, plasma abundance of lysine was negatively associated with patients' risk stratification. Taurine had higher plasma abundance in AML-M2 patients and plasma level of taurine was positively related with AML-M2 risk status, while the expression level of taurine transporter showed a negative correlation. Receiver operating characteristic curve analysis showed these four metabolites had high diagnostic value with lysine showing the highest sensitivity and specificity. These results suggest that plasma abundances of lysine and taurine may serve as potential metabolic biomarkers for the prognosis of patients with AML-M2.

Effects of different carbohydrate sources on taurine status in healthy Beagle dogs.

This study evaluated the effects of a grain-based (GB) and grain-free (GF) diet on protein utilization and taurine status in healthy Beagle dogs. Two practical dog diets sufficient in crude protein, sulfur amino acids, and taurine content were formulated with the same ingredients with exception of the carbohydrate sources. The GB contained sorghum, millet, and spelt while potatoes, peas, and tapioca starch were used in the GF. A total of 12 Beagle dogs were used in a completely randomized design with six replicates per treatment. The study consisted of an adaptation period of 2 wk followed by an experimental period of 28 d in which GB and GF were fed to the dogs. At the end of the adaptation period and every 2 wk after it (day 0, day 14, day 28), markers of taurine metabolism were analyzed in whole blood (taurine), plasma (taurine, methionine, and cystine), urine (taurine:creatinine), and fresh fecal samples (primary and secondary bile acids). Fecal samples were collected during the last 6 d of experimental period for digestibly assessment using titanium dioxide as an external marker. Taurine markers and digestibility data were analyzed in a repeated measures model and one-way ANOVA, respectively, using PROC GLIMMIX in SAS (version 9.4). Apparent crude protein digestibility was not affected by treatment, but dogs fed GF diet had lower apparent organic matter digestibility compared with those fed GB (P < 0.05). Greater plasma taurine concentrations were observed at days 14 and 28 compared with day 0; wherein dogs fed GF exhibited greater increase compared to those fed GB (P < 0.05). Whole blood taurine concentrations, plasma methionine concentrations, and urinary taurine:creatinine were also greater at days 14 and 28 compared with day 0 (P < 0.05), but no effect of diet was observed. Total bile acid excretion was similar between GF and GB groups, but dogs fed GF excreted a higher proportion of primary bile acids compared with those fed GB (25.49% vs. 12.09% at day 28, respectively). In summary, overall taurine status was not affected by dietary treatments, however, our results suggest that the higher content of oligosaccharides and soluble fibers in the GF diet may alter the composition of the fecal bile acid pool.

N-acyl taurines are endogenous lipid messengers that improve glucose homeostasis.

Fatty acid amide hydrolase (FAAH) degrades 2 major classes of bioactive fatty acid amides, the N-acylethanolamines (NAEs) and N-acyl taurines (NATs), in central and peripheral tissues. A functional polymorphism in the human FAAH gene is linked to obesity and mice lacking FAAH show altered metabolic states, but whether these phenotypes are caused by elevations in NAEs or NATs is unknown. To overcome the problem of concurrent elevation of NAEs and NATs caused by genetic or pharmacological disruption of FAAH in vivo, we developed an engineered mouse model harboring a single-amino acid substitution in FAAH (S268D) that selectively disrupts NAT, but not NAE, hydrolytic activity. The FAAH-S268D mice accordingly show substantial elevations in NATs without alterations in NAE content, a unique metabolic profile that correlates with heightened insulin sensitivity and GLP-1 secretion. We also show that N-oleoyl taurine (C18:1 NAT), the most abundant NAT in human plasma, decreases food intake, improves glucose tolerance, and stimulates GPR119-dependent GLP-1 and glucagon secretion in mice. Together, these data suggest that NATs act as a class of lipid messengers that improve postprandial glucose regulation and may have potential as investigational metabolites to modify metabolic disease.

ß-alanine supplementation induces taurine depletion and causes alterations of the retinal nerve fiber layer and axonal transport by retinal ganglion cells.

To study the effect of taurine depletion induced by ß-alanine supplementation in the retinal nerve fiber layer (RNFL), and retinal ganglion cell (RGC) survival and axonal transport. Albino Sprague-Dawley rats were divided into two groups: one group received ß-alanine supplementation (3%) in the drinking water during 2 months to induce taurine depletion, and the other group received regular water. After one month, half of the rats from each group were exposed to light. Retinas were analyzed in-vivo using Spectral-Domain Optical Coherence Tomography (SD-OCT). Prior to processing, RGCs were retrogradely traced with fluorogold (FG) applied to both superior colliculi, to assess the state of their retrograde axonal transport. Retinas were dissected as wholemounts, surviving RGCs were immunoidentified with Brn3a, and the RNFL with phosphorylated high-molecular-weight subunit of the neurofilament triplet (pNFH) antibodies. ß-alanine supplementation decreases significantly taurine plasma levels and causes a significant reduction of the RNFL thickness that is increased after light exposure. An abnormal pNFH immunoreactivity in some RGC bodies, their proximal dendrites and axons, and a further diminution of the mean number of FG-traced RGCs compared with Brn3a+RGCs, indicate that their retrograde axonal transport is affected. In conclusion, taurine depletion causes RGC loss and axonal transport impairment. Finally, our results suggest that care should be taken when ingesting ß-alanine supplements due to the limited understanding of their potential adverse effects.