Taurine deficiency associated with dilated cardiomyopathy and aging.

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

Examination of Taurine Chloramine and Taurine on LPS-Induced Acute Pulmonary Inflammatory in Mice.

The novel coronavirus disease (COVID-19), which is prevalent in the world, develops severe pneumonia, of which 30% have fatal acute respiratory distress and acute lung injury. At present, there is no established treatment method for ARDS, and it is desired to develop a therapeutic drug as soon as possible. While TauCl has been reported to have anti-inflammatory effects on culture cells, little information is available concerning in vivo experiments. In the present study, we evaluated the anti-inflammatory effect of taurine chloramine (TauCl), a taurine derivative, against LPS-induced pneumonia in mouse. The mice were pretreated with TauCl intraperitoneally before intratracheal administration of LPS. Additionally, we evaluated the effect of taurine treatment by maintaining the mice on drinking water containing 0.5% taurine. Two days after LPS injection, body weight was decreased by 9.5 %, while lung weight was increased due to the infiltration of inflammatory cells; TauCl attenuated the gain in lung weight. LPS-induced acute pneumonia caused an increase in cytokine/chemokine mRNA expression, including that of IL-1ß, -6, -17, TNF-α, and MCP-1. However, TauCl treatment attenuated IL-6 expression, but not that of the others although the induction of plasma IL-6 tended to be reduced by TauCl treatment. Importantly, a similar effect against LPS-induced acute lung inflammation was confirmed by taurine pretreatment. These findings suggest that TauCl treatment partially prevents IL-6 production induced by acute pneumonia in vivo.

Bioavailability of Tauropine After Oral Ingestion in Mouse.

In the present study, we investigated the pharmacokinetics of oral ingested tauropine which is a natural taurine derivative found in marine invertebrates, such as abalone, and in mouse. To measure tauropine in the blood, it was derivatized with phenyl isothiocyanate (PITC), and PITC-tauropine was separated by reverse-phase high-performance liquid chromatography (HPLC) and detected by ultraviolet absorbance. Tauropine was detectable in the blood obtained from mice intraperitoneally injected with tauropine. However, it was not detectable in blood obtained from orally treated mice. In conclusion, oral ingested tauropine may be poorly absorbed by the gastrointestinal tract and transported into the blood.

Taurine suppresses liquid-liquid phase separation of lysozyme protein.

Taurine is a compatible osmolyte that confers stability to proteins. Recent studies have revealed that liquid-liquid phase separation (LLPS) of proteins underlie the formation of membraneless organelles in cells. In the present study, we evaluated the role of taurine on LLPS of hen egg lysozyme. We demonstrated that taurine decreases the turbidity of the polyethylene glycol-induced crowding solution of lysozyme. We also demonstrated that taurine attenuates LLPS-dependent cloudiness of lysozyme solution with 0.5 or 1 M NaCl at a critical temperature. Moreover, we observed that taurine inhibits LLPS formation of a heteroprotein mix solution of lysozyme and ovalbumin. These data indicate that taurine can modulate the formation of LLPS of proteins.

Age-related decline in the taurine content of the skin in rodents.

Taurine, a sulfur-containing amino acid, occurs at high concentrations in the skin, and plays a role in maintaining the homeostasis of the skin. We investigated the effects of aging on the content and localization of taurine in the skin of mice and rats. Taurine was extracted from the skin samples of hairless mice and Sprague Dawley rats, and the taurine content of the skin was determined by high-performance liquid chromatography (HPLC). The results of the investigation revealed that the taurine content in both the dermis and epidermis of hairless mice declined significantly with age. Similar age-related decline in the skin taurine content was also observed in rats. In contrast, the taurine content in the sole remained unchanged with age. An immunohistochemical analysis also revealed a decreased skin taurine content in aged animals compared with younger animals, although no significant differences in the localization of taurine were observed between the two age groups. Supplementation of the drinking water of aged mice with 3% (w/v) taurine for 4 weeks increased the taurine content of the epidermis, but not the dermis. The present study showed for the first time that the taurine content of the skin decreased with age in mice and rats, which may be related to the impairment of the skin homeostasis observed with aging. The decreased taurine content of the epidermis in aged animals was able to be rescued by taurine supplementation.

Taurine-Conjugated Metabolites in Hearts.

Mammalian tissues, especially the heart, contain high concentrations of taurine, a beta-amino acid that possesses a variety of physiological functions. While it is well known that taurine reacts with several metabolites, such as bile acids and fatty acids, taurine-conjugated metabolites in the heart have not been specifically studied. Recently, we performed Liquid chromatography-mass spectrometry- (LC-MS-) based metabolome analysis, comparing metabolome profiles of hearts from taurine transporter knockout (TauTKO) mice and wild-type mice to identify differences in taurine-conjugated metabolite content of the two phenotypes. Comparison of the metabolite profiles revealed taurine-containing dipeptides, such as glutamyltaurine, which are present in wild-type but not in TauTKO hearts. These data suggest that taurine functions not only as a free osmolyte but also as a conjugated metabolite within the heart.

Taurine attenuates the development of hepatic steatosis through the inhibition of oxidative stress in a model of nonalcoholic fatty liver disease in vivo and in vitro.

Nonalcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease. It is characterized by the accumulation of triglyceride within hepatocytes. Taurine is a sulfur-containing-ß-amino acid that is widely distributed in mammalian tissues. The objective of this study was to examine the effects of taurine on the development of hepatic steatosis in a model of NAFLD in vivo and in vitro. Male C57BL/6J mice were fed a high-fat diet (HFD) supplemented with 2% (w/v) or 5% (w/v) taurine for 12 weeks. An in vitro study was performed in HepG2 cells loaded with fatty acids. Twelve weeks of supplementation with an HFD increased the hepatic lipid levels and oxidative stress as well as the body weight and liver weight. Taurine significantly suppressed these changes, which was accompanied by a decrease in the hepatic level of thiobarbituric acid-reactive substances (TBARS). In addition, taurine treatment suppressed the HFD-induced reduction of the enzyme activity of hepatic superoxide dismutase and catalase and the reduction of the hepatic level of reduced glutathione and ATP. In HepG2 cells, taurine suppressed the fatty acid-induced lipid accumulation, production of reactive oxygen species and TBARS level, and amelioration of the fatty acid-induced disruption of the mitochondrial membrane potential. These results showed that taurine was effective in alleviating hepatic steatosis by reducing oxidative stress. Taurine may, therefore, be of therapeutic value in reducing the risks associated with NAFLD.

Mass spectrometry-based metabolomics to identify taurine-modified metabolites in heart.

Taurine is an abundant beta-amino acid found in high concentration in mammalian tissues. Taurine possesses many beneficial functions in mammalian cells. There are also a variety of taurine-conjugated products formed between taurine and bile acids, fatty acids, chloramine, mitochondrial tRNA, etc., and some of these have been identified as functional compounds. In the present study, we identified taurine-conjugated metabolites using LC-MS-based metabolome analysis of heart extracts prepared from hearts of wild-type and taurine transporter-knockout (TauTKO) mice, the latter being severely taurine deficient. Comparison analysis of metabolites identified taurine-containing dipeptides, including glutamyltaurine, aspartyltaurine, isoleucyltaurine, and leucyltaurine, which are present in wild-type but not TauTKO hearts. Acyltaurines (taurine-conjugated fatty acids) and taurine-conjugated bile acids were also detected, with levels unchanged in the TauTKO heart in comparison to the wild-type heart. These results demonstrate that taurine exists not only in the standard free form within the heart, but also in multiple conjugated forms, whose functions in the heart remain to be discovered.

Tissue Taurine Depletion Induces Profibrotic Pattern of Gene Expression and Causes Aging-Related Cardiac Fibrosis in Heart in Mice.

Dietary taurine deficiency results in dilated cardiomyopathy in cats while in mice taurine deficiency produced by knocking out the taurine transporter (TauT) gene leads to a reduction in cardiac function with advancing age. The present study elucidated the involvement of cardiac fibrosis in the aging-dependent cardiac disorder of the TauT-knockout (TauTKO) mouse. Old (18-24-month-old) TauTKO mice, but not young (3-5-month-old) mice, exhibit cardiac fibrosis. Transcriptome microarray analysis revealed an increase in pro-fibrotic genes, such as S100A4, ACTA2 and CTGF, in both young and old TauTKO hearts. Based on transcriptome-pathway analysis the genes involved in "organization of extracellular matrix," such as LGALS3, are enriched in old TauTKO hearts compared to old wild-type hearts, suggesting the contribution of these genes to fibrosis. In conclusion, taurine depletion predisposes the heart to fibrosis, which leads to cardiac fibrosis upon aging.

Induction of Growth Differentiation Factor 15 in Skeletal Muscle of Old Taurine Transporter Knockout Mouse.

It has been identified that skeletal muscle is an endocrine tissue. Since skeletal muscle aging affects not only to muscle strength and function but to systemic aging and lifespan, myokines secreted from skeletal muscle may be crucial factors for intertissue communication during aging. In the present study, we investigated the expression of myokines associated with skeletal muscle aging in taurine transporter knockout (TauTKO) mice, which exhibit the accelerated skeletal muscle aging. Among transforming growth factor (TGF)-beta family genes, only growth and differentiation factor 15 (GDF15) was markedly higher (>3-fold) in skeletal muscle of old TauTKO mice compared with that of either young TauTKO mice or old wild-type mice. Circulating levels of GDF15 were also elevated in old TauTKO mice. An elevation in circulating GDF15 was also observed in very old (30-month-old) wild-type mice, while skeletal GDF15 levels were normal. The treatment of cultured mouse C2C12 myotubular cells with aging-related factors that mediate cellular stresses, such as oxidative stress (hydrogen peroxide) and endoplasmic reticulum stress (tunicamycin and thapsigargin), leads to an increase in GDF15 secretion. In conclusion, GDF15 is a myokine secreted by aging-related stress and may control aging phenotype.

Functional properties of anti-inflammatory substances from quercetin-treated Bifidobacterium adolescentis.

The genus Bifidobacterium is well known to have beneficial health effects. We discovered that quercetin and related polyphenols enhanced the secretion of anti-inflammatory substances by Bifidobacterium adolescentis. This study investigated characteristics of the anti-inflammatory substances secreted by B. adolescentis. The culture supernatant of B. adolescentis with quercetin reduced the levels of inflammatory mediators in activated macrophages. Spontaneous quercetin degradant failed to increase anti-inflammatory activity, while the enhancement of anti-inflammatory activity by quercetin was sustained after washout of quercetin. Physicochemical treatment of the culture supernatant indicated that its bioactive substances may be heat-stable, non-phenolic, and acidic biomolecules with molecular weights less than 3 kDa. Acetate and lactate have little or no effect on nitric oxide production. Taken together, the anti-inflammatory substances secreted by B. adolescentis may be small molecules but not short chain fatty acids. In agreement with these findings, stearic acid was tentatively identified as a bioactive candidate compound.

The Taurine Content of Japanese Seaweed.

Japanese and South Koreans have a dietary habit of eating seaweed. Although it is known that some seaweed contains taurine, there have been few detailed analyses on the taurine content of seaweed other than the major types of edible seaweed. In the present study, we determined the content of free amino acids, including taurine, in seaweed obtained along the Sea of Japan coast. The taurine content in the seaweed varied according to the species. Among the 29 different types of seaweed that were studied, red algae contained relatively high concentrations of taurine. In contrast, the taurine content was low or undetectable in brown and green algae. The algal alanine level was relatively higher in brown sea algae, which was in sharp contrast to its taurine level. No clear trends were observed with regards to the distribution of the other free amino acids, including aspartic acid, glutamic acid, and phenylalanine. Considering the physiological role of taurine in cellular homeostasis, the algal taurine content may be associated with the growing environment. Taurine-rich red edible algae such as mafunori (Gloiopeltis tenax)/fukurofunori (Gloiopeltis furcata), kabanori (Gracilaria textorii), and ogonori (Gracilaria vermiculophylla) may be used to create functional foods that are rich in naturally occurring taurine.

Taurine ameliorates cholesterol metabolism by stimulating bile acid production in high-cholesterol-fed rats.

This study was designed to investigate the effects of dietary taurine on cholesterol metabolism in high-cholesterol-fed rats. Male Sprague-Dawley rats were randomly divided into two dietary groups (n = 6 in each group): a high-cholesterol diet containing 0.5% cholesterol and 0.15% sodium cholate, and a high-cholesterol diet with 5% (w/w) taurine. The experimental diets were given for 2 weeks. Taurine supplementation reduced the serum and hepatic cholesterol levels by 37% and 32%, respectively. Faecal excretion of bile acids was significantly increased in taurine-treated rats, compared with untreated rats. Biliary bile acid concentrations were also increased by taurine. Taurine supplementation increased taurine-conjugated bile acids by 61% and decreased glycine-conjugated bile acids by 53%, resulting in a significant decrease in the glycine/taurine (G/T) ratio. Among the taurine-conjugated bile acids, cholic acid and deoxycholic acid were significantly increased. In the liver, taurine supplementation increased the mRNA expression and enzymatic activity of hepatic cholesterol 7α-hydroxylase (CYP7A1), the rate-limiting enzyme for bile acid synthesis, by three- and two-fold, respectively. Taurine also decreased the enzymatic activity of acyl-CoA:cholesterol acyltransferase (ACAT) and microsomal triglyceride transfer protein (MTP). These observations suggest that taurine supplementation increases the synthesis and excretion of taurine-conjugated bile acids and stimulates the catabolism of cholesterol to bile acid by elevating the expression and activity of CYP7A1. This may reduce cholesterol esterification and lipoprotein assembly for very low density lipoprotein (VLDL) secretion, leading to reductions in the serum and hepatic cholesterol levels.

Role of the osmolyte taurine on the folding of a model protein, hen egg white lysozyme, under a crowding condition.

Taurine is one of the osmolytes that maintain the structure of proteins in cells exposed to denaturing environmental stressors. Recently, cryoelectron tomographic analysis of eukaryotic cells has revealed that their cytoplasms are crowded with proteins. Such crowding conditions would be expected to hinder the efficient folding of nascent polypeptide chains. Therefore, we examined the role of taurine on the folding of denatured and reduced lysozyme, as a model protein, under a crowding condition. The results confirmed that taurine had a better effect on protein folding than did ß-alanine, which has a similar chemical structure, when the protein to be folded was present at submillimolar concentration. NMR analyses further revealed that under the crowding condition, taurine had more interactions than did ß-alanine with the lysozyme molecule in both the folded and denatured states. We concluded that taurine improves the folding of the reduced lysozyme at submillimolar concentration to allow it to interact more favorably with the lysozyme molecule. Thus, the role of taurine, as an osmolyte in vivo, may be to assist in the efficient folding of proteins.

Taurine and atherosclerosis.

Taurine is abundantly present in most mammalian tissues and plays a role in many important physiological functions. Atherosclerosis is the underlying mechanism of cardiovascular disease including myocardial infarctions, strokes and peripheral artery disease and remains a major cause of morbidity and mortality worldwide. Studies conducted in laboratory animal models using both genetic and dietary models of hyperlipidemia have demonstrated that taurine supplementation retards the initiation and progression of atherosclerosis. Epidemiological studies have also suggested that taurine exerts preventive effects on cardiovascular diseases. The present review focuses on the effects of taurine on the pathogenesis of atherosclerosis. In addition, the potential mechanisms by which taurine suppress the development of atherosclerosis will be discussed.

Potential role of taurine in the prevention of diabetes and metabolic syndrome.

Metabolic syndrome is characterized by the cluster of a number of metabolic abnormalities in the presence of underlying insulin resistance. The prevalence of metabolic syndrome has steadily increased in all populations worldwide. Taurine (2-aminoethanesulfonic acid) is a sulfur-containing amino acid that is involved in a variety of physiological functions. Clinical and experimental studies show that taurine intake may be beneficial in the prevention of metabolic syndrome including diabetes, obesity, dyslipidemia, and hypertension. This article reviews the effect of taurine on all of the components of metabolic syndrome. In addition, the possible mechanisms by which taurine prevents diabetes and metabolic syndrome are also discussed. Further study is needed to determine the role of taurine in the development of metabolic syndrome in humans, because there is presently limited clinical data available.

Effects of dietary seaweed on obesity-related metabolic status: a systematic review and meta-analysis of randomized controlled trials.

CONTEXT: Seaweed is a promising source of anti-obesity agents, including polysaccharides, proteins, polyphenols, carotenoids, and n-3 long-chain polyunsaturated fatty acids. The anti-obesity effects of such compounds may be due to several mechanisms, including inhibition of lipid absorption and metabolism, effect on satiety, and inhibition of adipocyte differentiation. OBJECTIVE: The aim of this study was to assess the evidence from human randomized controlled trials for the effects of seaweed on body-weight status as well as lipid and nonlipid parameters in adults with overweight and obesity. DATA SOURCES: Four databases-Medline, Scopus, Web of Science, and Cochrane Library-were searched from December 2022 to June 2023 using the following key words: Seaweed OR fucoxanthin OR alginates OR fucoidans OR phlorotannin's OR macroalgae OR marine algae AND obesity OR overweight OR BMI OR body mass index. DATA EXTRACTION: Eleven interventional studies (10 parallel and 1 crossover) were extracted. DATA ANALYSIS: Meta-analysis showed a significant effect, favoring the intervention group for BMI (body mass index) (standardized mean difference [SMD]: -0.40; 95% CI: -0.65 to -0.16 kg/m2; P = 0.0013) and percentage of fat mass (SMD: -1.48; 95% CI: -2.66% to -0.30%, P = 0.0138). The results were seen when refined or extracted brown seaweed (BMI) or only refined brown seaweed (% fat mass) were administered to participants for at least 8 weeks. Moreover, a significant overall effect of seaweed supplementation on total cholesterol (SMD: -7.72; 95% CI: -12.49 to -2.95 mg/dL; P = 0.0015) and low-density-lipoprotein cholesterol (SMD: -7.33; 95% CI: -11.64 to -3.02 mg/dL; P < 0.001) was noted. Any significant effects of seaweed on glucose metabolism were not shown. CONCLUSION: Edible seaweed supplementation shows potential for managing obesity and disorders of the blood lipid profile when administered to participants for at least 8 weeks. SYSTEMATIC REVIEW REGISTRATION: PROSPERO registration no. CRD42022378484 (www.crd.york.ac.uk/PROSPERO).

Using the Objective Structured Assessment of Technical Skills (OSATS) global rating scale to evaluate the skills of surgical trainees in the operating room.

PURPOSE: The education of surgical trainees should be based on an accurate evaluation of their surgical skill levels. In our hospital, the Objective Structured Assessment of Technical Skills (OSATS) is used for this purpose. We conducted this study to demonstrate the validity and accuracy of the OSATS for assessing surgical skills in the operating room (OR) setting. METHODS: Between January, 2007 and December, 2010, the OSATS global rating scale was used to assess several operations in which surgical trainees participated. We assessed ten surgical trainees who participated as the main surgeon or first assistant, and studied the correlation between their postgraduate year and their OSATS score. RESULTS: The median score of the global rating scale for each trainee improved with each year of experience. The median scores of all trainees in postgraduate years 3, 4, and 5 were significantly different (p < 0.001 for both the main surgeon and first assistant roles; Kruskal-Wallis test). CONCLUSION: Using the OSATS global rating scale to assess the surgical skills of trainees in the OR was feasible and effective.

Effects of Betulinic Acid on the Proliferation, Cellular Senescence, and Type 1 Interferon-Related Signaling Pathways in Human Dermal Fibroblasts.

Pentacyclic triterpenoids, including betulinic acid (BA), and their glycosides are abundant in fruits such as Zizyphus sp., Dillenia sp., and Azanza sp. These compounds exhibit various pharmacological activities in human cells. Here, we investigated the effects of BA on the cellular proliferation and senescence of cultured normal human dermal fibroblasts (NHDFs). BA treatment for 24-48 h increased the proliferation of low-passage young fibroblasts. Furthermore, BA reduced the proportion of senescent cells, as determined via the ß-galactosidase assay of high-passage NHDFs. DNA microarray analysis and subsequent validations via quantitative real-time polymerase chain reaction revealed that BA downregulates interferon (IFN)-inducible genes, including IFIT1, IFITM1, IFI6, MX1, and OAS2, which are upregulated in replicative senescent cells compared with the low-passage young cells (control). Enrichment analysis based on the microarray data predicted BA-induced suppression of the type I IFN signaling pathway. BA downregulated the expression of the IRF9 transcriptional factor downstream of the type 1 IFN signaling pathway. IFN-inducible genes were downregulated via IRF9 silencing using siRNA compared with the negative control treated with siRNA. Consistently, BA treatment reduced the proportion of senescent cells and IFN-inducible genes in etoposide-treated fibroblasts. Hence, BA alleviates cellular senescence via the inhibition of the type 1 IFN signaling pathway in dermal fibroblasts.

Taurine accelerates the synthesis of ceramides and hyaluronic acid in cultured epidermis and dermal fibroblasts.

Taurine is a sulfur-containing amino acid derivative that can be found in the majority of mammalian tissues. Taurine is also present in the skin and is involved in maintaining skin homeostasis by exerting osmoregulatory and antioxidant effects. Previous studies have indicated that taurine treatment is effective against age-, ultraviolet- or detergent-induced skin dysfunction. To determine the mechanism responsible for the beneficial actions of taurine in the skin, the present study aimed to evaluate the effects of taurine on epidermal components (ceramides and filaggrin) and on the dermal extracellular matrix, in three-dimensionally (3D) cultured epidermis and dermal fibroblasts, respectively. These cells were cultured in the presence of 3-50 mM taurine, and cells or culture medium were collected for analysis. The effects of taurine on transepidermal water loss (TEWL) in the skin and the expression of inflammatory cytokines, including IL-1α, IL-1ß and IL-1 receptor antagonist, were investigated in acetone-treated 3D-cultured epidermis using a Tewameter and reverse transcription-quantitative PCR (RT-qPCR), respectively. The mRNA expression levels of MMP-1 and hyaluronic acid (HA) production were measured in skin dermal fibroblasts using RT-qPCR and ELISA, respectively. Taurine was found to suppress acetone-induced elevation in TEWL in 3D-cultured epidermis. Taurine also stimulated the mRNA expression of ceramide synthase 4 and filaggrin, a major structural protein in the stratum corneum, in 3D-cultured epidermis. In skin dermal fibroblasts, taurine inhibited the IL-1α-stimulated mRNA and protein expression of MMP-1. In addition, taurine treatment increased HA synthase-2 mRNA expression and in turn HA production. Results from the present study suggest that the protective effect of taurine on the skin is associated with the enhancement of epidermal barrier component expression and modulation of dermal extracellular matrix metabolism.