Taurine Levels Research Articles

The distinct mechanism regulating taurine homeostasis in mice: Nutrient availability affects taurine levels in the liver and energy restriction influences it in the intestine.

Our previous findings indicate that caloric restriction (CR) stimulates the production and secretion of taurine-conjugated bile acids in mice. Subsequent processing by gut microbiota leads to increased levels of deconjugated bile acids, taurine, and various taurine conjugates in the intestine. Furthermore, we demonstrated that carbohydrate restriction and protein restriction, to a smaller extent, mirror the impact of CR in terms of hepatic production of bile acids but not their secretion. We hypothesized that modulating dietary macronutrient levels would influence taurine homeostasis in the liver and intestine of ad libitum-fed and CR animals. Ad libitum-fed male mice were allocated to receive either a control, low-protein (LP), low-fat (LF), or low-carbohydrate (LC) diet. Meanwhile, CR groups were given 80 % of their regular voluntary food intake as a control, high-protein (HP), high-fat (HF), or high-carbohydrate (HC) diet. While CR did not affect the taurine levels and its conjugates in the liver, alteration in carbohydrates and protein intake impacted it. Conversely, in the intestine, CR increased the amount of free and conjugated taurine, whereas the various diets did not affect it or disrupt the CR-specific phenotype. Notably, variations in diet composition impacted the expression of the taurine transporter (Slc6a6) and glutathione-S transferases (GST) in the intestine as well as cysteine dioxygenase (Cdo) in the liver. The liver and the intestine show distinct responses to dietary interventions, with hepatic taurine being affected by the diet composition, while intestinal taurine is governed by energy availability.

Genotype-Dependent Variations in Oxidative Stress Markers and Bioactive Proteins in Hereford Bulls: Associations with DGAT1, LEP, and SCD1 Genes.

The objective of this study is to assess the influence of genetic polymorphisms in DGAT1, LEP, and SCD1 on the oxidative stress biomarkers and bioactive protein levels in Hereford bulls. A total of sixty-eight bulls were analyzed at 22 months of age to assess growth metrics and carcass quality, with a focus on polymorphisms in these genes. The key markers of oxidative stress, including malondialdehyde (MDA), and the activities of antioxidant enzymes such as glutathione reductase (GluRed), glutathione peroxidase (GPx), and superoxide dismutase (SOD) were measured, alongside bioactive compounds like taurine, carnosine, and anserine. The results show that the TT genotype of DGAT1 is linked to significantly higher MDA levels, reflecting increased lipid peroxidation, but is also associated with higher GluRed and GPx activities and elevated levels of taurine, carnosine, and anserine, suggesting an adaptive response to oxidative stress. The LEP gene analysis revealed that the CC genotype had the highest MDA levels but also exhibited increased GPx and SOD activities, with the CT genotype showing the highest SOD activity and the TT genotype the highest total antioxidant status (TAS). The SCD1 AA genotype displayed the highest activities of GluRed, GPx, and SOD, indicating a more effective antioxidant defence, while the VA genotype had the highest MDA levels and the VV genotype showed lower MDA levels, suggesting protective effects against oxidative damage. These findings highlight genotype specific variations in the oxidative stress markers and bioactive compound levels, providing insights into the genetic regulation of oxidative stress and antioxidant defences, which could inform breeding strategies for improving oxidative stress resistance in livestock and managing related conditions.

Separate mechanisms regulating accumbal taurine levels during baseline conditions and following ethanol exposure in the rat

Ethanol-induced dopamine release in the nucleus accumbens (nAc) is associated with reward and reinforcement, and for ethanol to elevate nAc dopamine levels, a simultaneous increase in endogenous taurine is required within the same brain region. By employing in vivo microdialysis in male Wistar rats combined with pharmacological, chemogenetic and metabolic approaches, our aim with this study was to identify mechanisms underlying ethanol-induced taurine release. Our results demonstrate that the taurine elevation, elicited by either systemic or local ethanol administration, occurs both in presence and absence of action potential firing or NMDA receptor blockade. Inhibition of volume regulated anion channels did not alter the ethanol-induced taurine levels, while inhibition of the taurine transporter occluded the ethanol-induced taurine increase, putatively due to a ceiling effect. Selective manipulation of nAc astrocytes using Gq-coupled designer receptors exclusively activated by designer drugs (DREADDs) did not affect ethanol-induced taurine release. However, activation of Gi-coupled DREADDs, or metabolic inhibition using fluorocitrate, rather enhanced than depressed taurine elevation. Finally, ethanol-induced taurine increase was fully blocked in rats pre-treated with the L-type Ca2+-channel blocker nicardipine, suggesting that the release is Ca2+ dependent. In conclusion, while astrocytes appear to be important regulators of basal taurine levels in the nAc, they do not appear to be the main cells underlying ethanol-induced taurine release.

TRPC5 controls the adrenaline-mediated counter regulation of hypoglycemia.

Hypoglycemia triggers autonomic and endocrine counter-regulatory responses to restore glucose homeostasis, a response that is impaired in patients with diabetes and its long-term complication hypoglycemia-associated autonomic failure (HAAF). We show that insulin-evoked hypoglycemia is severely aggravated in mice lacking the cation channel proteins TRPC1, TRPC4, TRPC5, and TRPC6, which cannot be explained by alterations in glucagon or glucocorticoid action. By using various TRPC compound knockout mouse lines, we pinpointed the failure in sympathetic counter-regulation to the lack of the TRPC5 channel subtype in adrenal chromaffin cells, which prevents proper adrenaline rise in blood plasma. Using electrophysiological analyses, we delineate a previously unknown signaling pathway in which stimulation of PAC1 or muscarinic receptors activates TRPC5 channels in a phospholipase-C-dependent manner to induce sustained adrenaline secretion as a crucial step in the sympathetic counter response to insulin-induced hypoglycemia. By comparing metabolites in the plasma, we identified reduced taurine levels after hypoglycemia induction as a commonality in TRPC5-deficient mice and HAAF patients.

B-283 Biological Consequences of Nitrous Oxide Abuse: Insights from Targeted Metabolomics Investigation

Abstract Background The recreational use of nitrous oxide (N2O), commonly known as laughing gas, has experienced a notable surge in popularity in recent times. According to the European Monitoring Centre for Drugs and Drug Addiction (EMCDDA), N2O is recognized as one of the most widely used psychoactive substances in Europe as of 2022. Its use also extends to Asia and America, according to literature. However, prolonged consumption of N2O has been associated with neurological complications linked to the functional inactivation of vitamin B12, disrupting One Carbon Metabolism. This study aims to explore the metabolic effects of N2O intoxication through a targeted metabolomics approach. Methods We conducted a prospective collection of clinical and biological information from 37 N2O users and 37 non-users (control group). Utilizing a targeted metabolomics method, we analyzed plasma amino acids using liquid chromatography coupled with mass spectrometry. Our statistical analysis encompassed principal component analyses, random forests, Mann-Whitney tests, Student's t-tests, and Spearman rank tests. Results Metabolomic analyses have demonstrated effective differentiation between patient groups. In comparison to controls, N2O consumers displayed reduced plasma levels of taurine, cystine, and methionine, alongside elevated plasma levels of serine and sarcosine. These findings suggest a potential influence of N2O on the cystine-methionine metabolic pathway. The decrease in methionine levels may be attributed to the decreased activity of methionine synthase (MS) due to vitamin B12 inactivation, which could partially explain the observed increase in serine levels. The rise in sarcosine levels could be explained by an increase in betaine-homocysteine S-methyltransferase (BHMT) activity. Moreover, dysfunction in cystathionine-β-synthase (CBS) or cystathionine γ-lyase (γ-CYS) may lead to the accumulation of upstream metabolites (such as serine) and a reduction in downstream metabolites (such as cysteine and taurine). Conclusions This study sheds light on potential new impacts of N2O, particularly on the plasma levels of serine, cystine, and taurine, indicating a potential modulation of enzymes involved in the conversion of homocysteine to taurine (CBS and/or γ-CYS). Additional investigations are required in a larger group of patients, which corresponds to the aims of the EFLM Task & Finish Group: Biomarkers of Diagnosis and Follow-up of Nitrous Oxide Abuse: https://www.eflm.eu/site/who-we-are/committee/science-committee/fu/tfg-biomarkers-of-diagnosis

Taurine ameliorates radiation-induced oxidative stress in bone marrow mesenchymal stromal cells and promotes osteogenesis.

Osteoradionecrosis of the jaw (ORNJ) is a severe complication following head and neck radiotherapy that significantly impacts the quality of life of patients. Currently, there is a lack of comprehensive understanding of the microenvironmental factors involved in ORNJ. In this study, we reveal the activation of taurine metabolism in irradiated mandibular stromal cells using scRNA-Seq and demonstrate a decrease in taurine levels in irradiated bone marrow mesenchymal stromal cells (BMSCs) through metabolomics. Compared with unirradiated BMSCs, taurine uptake in irradiated BMSCs increases. Taurine concentrations in the peripheral blood and jaws of irradiated mice are significantly lower than those in unirradiated mice (P = 0.0064 and 0.0249 respectively). Supplementation with taurine promotes osteogenic differentiation, reduces oxidative stress, and decreases DNA damage in irradiated BMSCs. Oral administration of taurine significantly improves the survival rate of irradiated mice and enhances osteogenesis in irradiated jaws. Our study highlights the role of taurine in the recovery from radiation-induced jaw injury, and suggests its potential as a non-invasive therapeutic option for combating ORNJ.

Taurine can play a positive role in growth, liver health and resistance to Aeromonas hydrophila of yellow catfish Pelteobagrus fulvidraco exposed to ammonia stress for a long time

Ammonia is an important environmental pollutant that is toxic to most aquatic animals, and nutrient manipulation is an effective regulatory pathway. To assess the influence of taurine supplementation on growth, liver detoxification and anti-bacterial infection of yellow catfish subjected to ammonia exposure for a long time, three experiment diets with different taurine levels (0.50, 1.00, and 2.00 %) were formulated and fed to fish (7.28 ± 0.05) g under three ammonia levels (0.00, 25.00 and 50.00 mg/L total ammonia nitrogen) for 56 days. The results showed that hepatic glycogen and whole-body protein contents were reduced, suggesting that energy deficiency caused by ammonia poisoning plays an important role in growth inhibition; elevated serum alanine aminotransferase and aspartate aminotransferase levels suggest liver injury, which may be caused by oxidative stress (decreased activities of superoxide dismutase and catalase, and expressions of SOD and CAT) and inflammation (increased contents of tumor necrosis factor α, interleukin 1 and interleukin 8, and expressions of TNF α, IL 1 and IL8), analysis of tissue sections further confirmed this finding. Furthermore, after injection with Aeromonas hydrophila, cumulative mortality increased proportionally with the rise in ammonia levels, the observed decrease in serum complements C3, C4, immunoglobulin M, and antibody titer contents emerged as a crucial factor contributing to the decreased disease resistance. The exogenous taurine was found to alleviate the negative impact of the above-mentioned ammonia poisoning. This study provides valuable insights into the mechanism of ammonia-induced aquatic toxicology in fish.

Differential One-Carbon Metabolites among Children with Autism Spectrum Disorder: A Case-Control Study

BackgroundDriven by the complex multifactorial etiopathogenesis of autism spectrum disorder (ASD), a growing interest surrounds the disturbance in folate-dependent one-carbon metabolism (OCM) in the pathology of ASD, whereas the evidence remained inconclusive. ObjectivesThe study aims to investigate the association of OCM metabolism and ASD and characterize differential OCM metabolites among children with ASD. MethodsPlasma OCM metabolites were investigated in 59 children with ASD and 40 neurotypical children using ultra-performance liquid chromatography tandem mass spectrometry technology. Differences (significance level < 0.001) were tested in each OCM metabolite between cases and controls. Multivariable models were also performed after adjusting for covariates. ResultsTen out of 22 examined OCM metabolites were significantly different in children with ASD, compared with neurotypical controls. Specifically, S-adenosylmethionine (SAM), oxidized glutathione (GSSG), and glutathione (GSH) levels were increased, whereas S-adenosylhomocysteine (SAH), choline, glycine, L-serine, cystathionine, L-cysteine, and taurine levels were significantly decreased. Children with ASD showed significantly higher SAM/SAH ratio (3.87 ± 0.93 compared with 2.00 ± 0.76, P = 0.0001) and lower GSH/GSSG ratio [0.58 (0.46, 0.81) compared with 1.71 (0.93, 2.99)] compared with the neurotypical controls. Potential interactive effects between SAM/SAH ratio, taurine, L-serine, and gastrointestinal syndromes were further observed. ConclusionsOCM disturbance was observed among children with ASD, particularly in methionine methylation and trans-sulfuration pathways. The findings add valuable insights into the mechanisms underlying ASD and the potential of ameliorating OCM as a promising therapeutic of ASD, which warrant further validation.

Excitation–contraction coupling reflects the metabolic profile of mantle muscle in young cuttlefish (Sepia officinalis)

AbstractThe mantle muscle of common cuttlefish, Sepia officinalis, is responsible both for high‐magnitude and rapid movements for locomotion, as well as sustained ventilation, which require specific metabolic, electrophysiological, and structural organization. Young cuttlefish have a highly oxidative phenotype and a rapid growth rate. Here, we show high rates of oxygen consumption and protein synthesis in juveniles, and these rates decay exponentially over the first few weeks of growth. This is associated with considerable citrate synthase activity (relative to larger cuttlefish) but a lack of glucose metabolism based on zero uptake of glucose by isolated muscle sheets and minimal activity of hexokinase (similar to larger animals). In contrast to glucose metabolism in the heart, glucose metabolism in these muscle sheets was not stimulated by extracellular taurine. Previous research revealed an unusual ion channel complement in mantle myocytes, the most notable feature of which is the lack of a Na+ current during depolarization. Because this adaptation is not consistent across the coleoid clade, we investigated excitation–contraction coupling. Here, mantle energetics and contractility, including the individual components of the total Ca2+ flux driving contraction, were studied. Results indicate that the majority of Ca2+ current underlying contractile stress development capacity in cuttlefish juveniles is not mediated by dihydropyridine‐sensitive L‐type channels, in contrast to their adult counterparts, and the sarcoplasmic reticulum contributes little to routine contractility. We had previously noted an influence of physiological levels of taurine in limiting cardiac contractility but found no analogous sensitivity in mantle muscle. Finally, transmission electron microscopy of subcellular architecture revealed the presence of sarcoplasmic tubular aggregates, suggesting that oxidative inhibition of sarcoplasmic reticulum function limits its role in this life stage.

Investigation of the anti-skin aging effects of taurine through mendelian randomization analysis of its relationship with immune cells.

Aging skin, exacerbated by external factors like UV radiation and pollutants, is a major cosmetic concern. Taurine, renowned for its antioxidant and anti-inflammatory properties, may combat skin aging. We performed mendelian randomization (MR) analysis to investigate the causal link between taurine and immune cells linked to skin aging. To investigate the association between taurine and immune cells using mendelian randomization, to thereby explore the mechanism through which taurine exerts anti-aging effects on the skin via immune modulation. A MR approach was employed using taurine-level data from the Ieu Open GWAS Project and immunocyte traits from a large European cohort. MR-Egger regression, weighted median estimation, and inverse variance weighting all provided statistical insights into causality. Sensitivity analyses assessed the heterogeneity and pleiotropy among the genetic instruments used. MR analysis identified a causal relationship between taurine levels and 10 immunocyte phenotypes, with taurine found to be negatively and positively associated with three and seven phenotypes, respectively. Sensitivity analysis revealed no significant heterogeneity or pleiotropy, suggesting reliable MR findings. This study provides insights into the immunological pathways by which taurine contributes to skin anti-aging effects, suggesting that increasing taurine levels could offer a novel strategy for anti-aging skincare.

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.

Gut microbiota, dietary taurine, and fiber shift taurine homeostasis in adipose tissue of calorie-restricted mice to impact fat loss

Previously, we demonstrated that caloric restriction (CR) stimulates the synthesis, conjugation, secretion, and deconjugation of taurine and bile acids in the intestine, as well as their reuptake. Given taurine's potent antiobesogenic properties, this study aimed to assess whether the CR-induced shift in taurine homeostasis contributes to adipose tissue loss. To verify that, male C57Bl/6 mice were subjected to 20% CR or ad libitum feeding, with variations in cage bedding and gut microbiota conditions. Additional groups received taurine supplementation or were fed a low-taurine diet (LTD). The results showed that in CR animals, taurine derived from the intestine was preferentially trafficked to epididymal white adipose tissue (eWAT) over other tested organs. Besides increased levels of taurine transporter TauT, gene expression of Cysteine dioxygenase (Cdo) involved in taurine synthesis was upregulated in CR eWAT. Taurine concentration in adipocytes was inversely correlated with fat pad weight of CR mice. Different types of cage bedding did not impact eWAT taurine levels; however, the lack of bedding and consumption of a diet high in soluble fiber did. Depleting gut microbiota with antibiotics or inhibiting bile salt hydrolase (BSH) activity reduced WAT taurine concentration in CR mice. Taurine supplementation increased taurine levels in WAT and brown adipose tissue (BAT), promoting fat loss in CR animals. LTD consumption blunted WAT loss in CR animals, with negligible impact on BAT. This study provides multiple insights into taurine's role in CR-triggered fat loss and describes a novel communication path between the liver, gut, microbiota, and WAT, with taurine acting as a messenger.

Metabolic profiling of psoriasis vulgaris and palmoplantar pustulosis.

Psoriasis is a chronic inflammatory skin disorder with various subtypes, including psoriasis vulgaris (PV) and palmoplantar pustulosis (PPP). Metabolomics studies have provided insights into psoriasis pathogenesis. However, research on metabolomic alterations in PV and PPP patients is limited. We aimed to explore and compare the metabolic profiles of patients with PV and PPP to those of healthy volunteers (HVs). A single-centre retrospective cohort was constructed, comprising Korean patients with psoriasis and HVs matched by age and sex. Clinical information including demographics, disease severity, and comorbidities were collected. Plasma samples were subjected to targeted metabolic analysis using an Absolute IDQ®p180 kit, which quantified 188 metabolites, including amino acids and carnitines. Statistical significance was assessed using an independent t-test and chi-square test, with p-values adjusted by the Benjamini-Hochberg procedure. Pathway analyses were employed to gain a comprehensive understanding of the metabolite profile. This study included 93 patients (73 PV and 20 PPP) and an equal number of HVs. PV patients showed increased levels of sarcosine, serotonin, propionylcarnitine, proline, aspartic acid, tyrosine, taurine, spermine and ornithine, but exhibited a decreased level of acetylcarnitine than matched HVs. Notably, sarcosine levels were significantly elevated in PPP patients. Furthermore, the sarcosine/glycine ratio was significantly higher in both PV and PPP patients than in HVs. Pathway analysis showed significant increases in metabolites involved in amino acid metabolism and the urea cycle in PV patients. In conclusion, this study demonstrated distinct metabolic profiles in PV and PPP patients compared to HVs, suggesting sarcosine as a potential biomarker for psoriasis.

Hypoxic-Ischemic Insult Alters Polyamine and Neurotransmitter Abundance in the Specific Neonatal Rat Brain Subregions.

Neonatal hypoxic-ischemic (HI) brain insult is a major cause of neonatal mortality and morbidity. To assess the underlying pathological mechanisms, we mapped the spatiotemporal changes in polyamine, amino acid, and neurotransmitter levels, following HI insult (by the Rice-Vannucci method) in the brains of seven-day-old rat pups. Matrix-assisted laser desorption/ionization mass spectrometry imaging of chemically modified small-molecule metabolites by 4-(anthracen-9-yl)-2-fluoro-1-methylpyridin-1-ium iodide revealed critical HI-related metabolomic changes of 22 metabolites in 14 rat brain subregions, much earlier than light microscopy detected signs of neuronal damage. For the first time, we demonstrated excessive polyamine oxidation and accumulation of 3-aminopropanal in HI neonatal brains, which was later accompanied by neuronal apoptosis enhanced by increases in glycine and norepinephrine in critically affected brain regions. Specifically, putrescine, cadaverine, and 3-aminopropanal increased significantly as early as 12 h postinsult, mainly in motor and somatosensory cortex, hippocampus, and midbrain, followed by an increase in norepinephrine 24 h postinsult, which was predominant in the caudate putamen, the region most vulnerable to HI. The decrease of γ-aminobutyric acid (GABA) and the continuous dysregulation of the GABAergic system together with low taurine levels up to 36 h sustained progressive neurodegenerative cellular processes. The molecular alterations presented here at the subregional rat brain level provided unprecedented insight into early metabolomic changes in HI-insulted neonatal brains, which may further aid in the identification of novel therapeutic targets for the treatment of neonatal HI encephalopathy.

Effect of taurine on growth and immune response of Pacific white shrimp (Litopenaeus vannamei) cultured at different temperatures

Low temperature is a common challenge in the culture of Pacific white shrimp (Litopenaeus vannamei), and taurine is a potential nutrient that may improve its cold-resistance. This experiment aimed to investigate effects of dietary taurine on growth and immune response of Pacific white shrimp cultured at normal and cold temperatures. Six diets were supplemented with increasing levels of taurine (0, 0.2, 0.4, 0.6, 0.8 and 1.0%) and fed to shrimp (1.59 ± 0.03 g) reared at two water temperatures (28 °C and 20 °C) for 8 weeks. The results showed that compared with 28 °C, shrimp reared at 20 °C showed lower growth performance, feed utilization, apparent digestibility and total hemocyte count (THC) (P < 0.05), but higher content of serum glucose, intracellular reactive oxygen species (ROS) and Ca2+, malonaldehyde (MDA) and apoptosis rate (P < 0.05), indicating a higher risk of oxidative damage during low temperature stress. Interestingly, shrimp could cope with cold stress by changing hemocyte composition, increasing antioxidant enzyme activity and genes expression of apoptosis and autophagy. The effect of taurine was different at different temperatures. At 28 °C, taurine supplementation improved growth rate of shrimp by increasing digestive enzyme activities, digestion absorption rate and nutrient utilization. Based on the quadratic model of weight gain rate, feed efficiency, protein retention efficiency and the broken line model of apparent digestibility coefficients of protein, the amount of taurine required for shrimp reared at 28 °C was 0.57–0.60% of dry diet. At 20 °C, taurine increased the number of THC, granulocytes, semi-granulocytes, the activities of antioxidant enzymes such as superoxide dismutase and catalase, and decreased the content of ROS in the cells, which may enhance cold resistance of shrimp. Moreover, taurine supplementation down-regulated mRNA expression of cell apoptosis genes (cyt-c, caspase-9 and caspase-3) and up-regulated mRNA expression of cell autophagy genes (atg1, atg13, atg7 and lc3) (P < 0.05), which may help to maintain cell stability at 20 °C. The optimal requirement of taurine in shrimp reared at 20 °C was 0.56–0.66% of dry diet in this experiment based on THC and MDA content. In conclusion, our study suggests that appropriate taurine promotes growth and feed utilization at optimal temperature and enhances the stability of hemocyte at low temperature in white shrimp.

Metabolomic and sphingolipidomic profiling of human hepatoma cells exposed to widely used pharmaceuticals

Pharmaceutical compounds have become one of the main contaminants of emerging concern (CECs) due to their high usage and increased release into the environment. This study aims to assess the effects caused by three widely consumed hepatotoxic pharmaceutical compounds: an antibiotic (amoxicillin), an antiepileptic (carbamazepine), and an antidepressant (trazodone), on human health when indirectly exposed to toxicologically relevant concentrations (30, 15, and 7.5 μM for amoxicillin and carbamazepine, and 4, 2, and 1 μM for trazodone). A combination of semi-targeted metabolomic and targeted sphingolipid analyses was chosen to unravel the metabolic alterations in human hepatic cells exposed to these CECs at three concentrations for 24 h. HepG2 hepatoma cells were encapsulated in sodium alginate spheroids to improve the physiological relevance of this in vitro approach. Statistical analysis was used to identify the most affected metabolites and sphingolipids for each drug exposure. The results revealed small but significant changes in response to carbamazepine and trazodone exposures, affecting sphingolipid, glycerophospholipid precursors, and amino acid metabolism. Under both drug treatments, a decrease in various ceramide species (related to cell signaling) was observed, along with reduced taurine levels (related to the biosynthesis of bile acid conjugates) and carnitine levels (suggesting an impact on energy production). These and other drug-specific changes indicate that cellular functions in liver cells might be altered under low doses of these CECs, potentially affecting the health of other organs.

Oleuropein mitigates non-alcoholic fatty liver disease (NAFLD) and modulates liver metabolites in high-fat diet-induced obese mice via activating PPARα.

This study aimed to elucidate the mechanism of oleuropein (OLE) ameliorates non-alcoholic fatty liver disease (NAFLD) and its underlying mechanisms. Male C57BL/6J mice were fed either a low-fat diet (LFD), a high-fat diet (HFD), or a HFD supplemented with 0.03% (w/w) OLE for 16 weeks. OLE supplementation decreased body weight and liver weight, improved serum lipid profiles, and ameliorated HFD-induced hepatic dysfunction. Liver metabolomics analysis revealed that OLE increased the levels of nicotinamide, tauroursodeoxycholic acid, taurine, and docosahexaenoic acid, which were beneficial for lipid homeostasis and inflammation regulation. OLE exerted its protective effects by activating peroxisome proliferator-activated receptor alpha (PPARα), a key transcription factor that regulates fibroblast growth factor 21 (FGF21) expression and modulates lipid oxidation, lipogenesis and inflammation pathways. Importantly, OLE supplementation did not significantly affect body weight or liver weight in PPARα knockout (PPARα KO) mice, indicating that PPARα is essential for OLE-mediated NAFLD prevention. Our results suggest that OLE alleviates NAFLD in mice by activating PPARα and modulating liver metabolites. © 2024 Society of Chemical Industry.

Dietary Taurine Improves The Growth Performance, Health Status and Liver Histopathology of Meagre (Argyrosomus Regius) Fed A Reduced Fish Meal Diet

Abstract Research has focused on alternative plant materials or additives that can be used instead of fish meal due to limited stocks and increased feed prices, although it is important for carnivorous fish species. Taurine is a functional amino acid supplemented to low fish meal diets to improve the growth performance of fish. In this study, eight experimental diets with 0%, 0.5%, 1% and 2% ratios of taurine supplemented (T0, T0.5, T1 and T2) high (HFM) and low fish meal (LFM) diets were prepared (defined as HFMT0, HFMT0.5, HFMT1, HFMT2, LFMT0, LFMT0.5, LFMT1 and LFMT2). The experiment was carried out in twenty-four 400 L rectangular fiberglass tanks conducted in a marine water system, and fish (initial mean weight of 23.5 g) were stocked in each tank. The nutrition trial was carried out for 90 days with three replicates. Meagre fed with the HFMT1 diet had a higher final mean weight (FMW) and specific growth rate (SGR) than fish fed with HFMT0 and all LFM diets. Including taurine in all LFM diets also enhanced growth performance. The FMW and SGR of fish fed the LFMT0.5 diet were similar when compared to HFMT0 (P&gt;0.05) and increased compared to that of other LFM diets with taurine (P&lt;0.05). Meagre fed the LFM0.5 diet had a lower feed conversion rate (FCR) than those provided for all HFM diets, although there was no significant difference between treatments. Dietary taurine has decreased the hepatosomatic index (HSI), viscerosomatic index (VSI) and total ammonia-nitrogen excretion (TAN), irrespective of taurine and fish meal levels. Including dietary taurine at both fish meal levels enhances the number of red blood cells (RBC) and whole-body amino acids of meagre. The most remarkable conclusion of this study is the inclusion of taurine in low fish meal diets improved growth performance and profitability in meagre, and the level of 0.5% has been recommended.

Chronic effects of exposure to polyethylene microplastics may be mitigated at the expense of growth and photosynthesis in reef-building corals

The causes of the physiological effects of microplastic pollution, potentially harming reef-building corals, are unclear. Reasons might include increased energy demands for handling particles and immune reactions. This study is among the first assessing the effects of long-term microplastic exposure on coral physiology at realistic concentrations (200 polyethylene particles L−1). The coral species Acropora muricata, Pocillopora verrucosa, Porites lutea, and Heliopora coerulea were exposed to microplastics for 11 months, and energy reserves, metabolites, growth, and photosymbiont state were analyzed. Results showed an overall low impact on coral physiology, yet species-specific effects occurred. Specifically, H. coerulea exhibited reduced growth, P. lutea and A. muricata showed changes in photosynthetic efficiency, and A. muricata variations in taurine levels. These findings suggest that corals may possess compensatory mechanisms mitigating the effects of microplastics. However, realistic microplastic concentrations only occasionally affected corals. Yet, corals exposed to increasing pollution scenarios will likely experience more negative impacts.

Modeling of Intracellular Taurine Levels Associated with Ovarian Cancer Reveals Activation of p53, ERK, mTOR and DNA-Damage-Sensing-Dependent Cell Protection.

Taurine, a non-proteogenic amino acid and commonly used nutritional supplement, can protect various tissues from degeneration associated with the action of the DNA-damaging chemotherapeutic agent cisplatin. Whether and how taurine protects human ovarian cancer (OC) cells from DNA damage caused by cisplatin is not well understood. We found that OC ascites-derived cells contained significantly more intracellular taurine than cell culture-modeled OC. In culture, elevation of intracellular taurine concentration to OC ascites-cell-associated levels suppressed proliferation of various OC cell lines and patient-derived organoids, reduced glycolysis, and induced cell protection from cisplatin. Taurine cell protection was associated with decreased DNA damage in response to cisplatin. A combination of RNA sequencing, reverse-phase protein arrays, live-cell microscopy, flow cytometry, and biochemical validation experiments provided evidence for taurine-mediated induction of mutant or wild-type p53 binding to DNA, activation of p53 effectors involved in negative regulation of the cell cycle (p21), and glycolysis (TIGAR). Paradoxically, taurine's suppression of cell proliferation was associated with activation of pro-mitogenic signal transduction including ERK, mTOR, and increased mRNA expression of major DNA damage-sensing molecules such as DNAPK, ATM and ATR. While inhibition of ERK or p53 did not interfere with taurine's ability to protect cells from cisplatin, suppression of mTOR with Torin2, a clinically relevant inhibitor that also targets DNAPK and ATM/ATR, broke taurine's cell protection. Our studies implicate that elevation of intracellular taurine could suppress cell growth and metabolism, and activate cell protective mechanisms involving mTOR and DNA damage-sensing signal transduction.