Taurine supplementation in high-fat diet fed male mice attenuates endocrine pancreatic dysfunction in their male offspring.

Obesity in fathers leads to DNA damage and epigenetic changes in sperm that may carry potential risk factors for metabolic diseases to the next generation. Taurine (TAU) supplementation has demonstrated benefits against testicular dysfunction and pancreatic islet impairments induced by obesity, but it is not known if these protective actions prevent the propagation of metabolic disruptions to the next generation; as such, we hypothesized that paternal obesity may increase the probability of endocrine pancreatic dysfunction in offspring, and that this could be prevented by TAU supplementation in male progenitors. To test this, male C57Bl/6 mice were fed on a control diet (CTL) or a high-fat diet (HFD) without or with 5% TAU in their drinking water (CTAU and HTAU) for 4 months. Subsequently, all groups of mice were mated with CTL females, and the F1 offspring were identified as: CTL-F1, CTAU-F1, HFD-F1, and HTAU-F1. HFD-fed mice were normoglycemic, but glucose intolerant and their islets hypersecreted insulin. However, at 90 days of age, HFD-F1 offspring displayed normal glucose homeostasis and adiposity, but reduced glucose-induced insulin release. HFD-F1 islets also exhibited ß- and α-cell hypotrophy, and lower δ-cell number per islet. Paternal TAU supplementation prevented the decrease in glucose-induced insulin secretion and normalized ß-cell size and δ-cell number, and increased α-cell size/islet in HTAU-F1 mice. In conclusion, HFD consumption by male founders decreases ß-cell secretion and islet-cell distribution in their offspring. TAU attenuates the deleterious effects of paternal obesity on insulin secretion and islet-cell morphology in F1 offspring.

Taurine supplementation regulates Iκ-Bα protein expression in adipose tissue and serum IL-4 and TNF-α concentrations in MSG obesity.

PURPOSE: Obesity is usually associated with low-grade inflammation, which impairs insulin action. The amino acid, taurine (TAU), regulates glucose homeostasis and lipid metabolism and presents anti-inflammatory actions. Here, we evaluated whether inflammatory markers are altered in the serum and retroperitoneal adipose tissue of monosodium glutamate (MSG) obese rats, supplemented or not with TAU. METHODS: Male Wistar rats received subcutaneous injections of MSG (4 mg/kg body weight/day, MSG group) or hypertonic saline (CTL) during the first 5 days of life. From 21 to 120 days of age, half of each of the MSG and CTL groups received 2.5 % TAU in their drinking water (CTAU and MTAU). RESULTS: At 120 days of age, MSG rats were obese and hyperinsulinemic. TAU supplementation reduced fat deposition without affecting insulinemia in MTAU rats. MSG rats presented increased pIκ-Bα/Iκ-Bα protein expression in the retroperitoneal adipose tissue. TAU supplementation decreased the ratio of pIκ-Bα/Iκ-Bα protein, possibly contributing to the increased Iκ-Bα content in MTAU adipose tissue. Furthermore, MSG obesity or supplementation did not alter TNF-α, IL-1ß or IL-6 content in adipose tissue. In contrast, MSG rats presented lower serum TNF-α, IL-4 and IL-10 concentrations, and these alterations were prevented by TAU treatment. CONCLUSION: MSG obesity in rats was not associated with alterations in pro-inflammatory markers in retroperitoneal fat stores; however, reductions in the serum concentrations of anti-inflammatory cytokines and of TNF-α were observed. TAU treatment decreased adiposity, and this effect was associated with the normalization of circulating TNF-α and IL-4 concentrations in MTAU rats.

Improvement in the expression of hepatic genes involved in fatty acid metabolism in obese rats supplemented with taurine.

AIMS: Fat deposition in the liver, which leads to nonalcoholic fatty liver disease is associated with obesity. Taurine (Tau) regulates lipid metabolism, representing a possible nutraceutical agent against obesity and its comorbidities. Here, we investigated whether Tau supplementation prevents hepatic lipid accumulation by regulation of the main hepatic genes involved in de novo lipogenesis and ß-oxidation. MAIN METHODS: Male rats received subcutaneous injections of monosodium glutamate (MSG; 4 mg/kg body weight/day) or saline (control group, CTL) during the first 5 days of life. From 21 to 120 days of age, half of each of the MSG and CTL groups received 2.5% Tau in drinking water (CTau and MTau). KEY FINDINGS: MSG-treated rats were normoglycemic, hypertriglyceridemic and insulin resistant (IR). MSG rats also exhibited massive obesity and higher hepatic triglyceride (TG) content. This effect was associated with enhanced gene expression of fatty acid synthase (FASN), but reduced carbohydrate response element-binding protein (ChREBP), microsomal TG transfer protein (MTP) and carnitine palmitoyltransferase (CPT)-1a mRNAs in MSG livers. Tau supplementation decreased whole body fat accumulation and serum TG levels, without altering IR. Tau also normalized hepatic TG content by enhancing ChREBP, MTP, peroxisome proliferator-activated receptor (PPAR)-α, ACO (acyl-CoA oxidase) and CPT-1a gene expressions. SIGNIFICANCE: Therefore, increased hepatic TG deposition in MSG-obese rats is associated with an enhanced FASN, and reduced MTP and CPT-1a genes. Tau supplementation prevented obesity and hepatic TG deposition by upregulating MTP mRNA, ameliorating hepatic lipid efflux, and consequently enhancing PPAR-α which increases lipid oxidation through ACO and CPT-1a gene expressions.

Influence of different frequencies of transcutaneous electrical nerve stimulation on the threshold and pain intensity in young subjects.

OBJECTIVE: To investigate the effects of different transcutaneous electrical nerve stimulation frequencies in nociception front of a pressure pain threshold and cold in healthy individuals. METHODS: Twenty healthy subjects were divided into four groups, all of which have gone through all forms of electrical stimulation at different weeks. Assessments were pre and post-therapy, 20 and 60 minutes after stimulation. To evaluate the pressure pain threshold, an algometer was used with one tapered tip, pressing the hypothenar region until voluntary report the word "pain". Cold pain intensity was assessed by immersion in water at 5°C for 30 seconds; at the end, the subject was asked to quantify the pain intensity on a Visual Analog Scale for Pain. For electrical stimulation, two electrodes were used near the elbow, for 20 minutes, with an intensity strong, but not painful. The frequency was in accordance with the group: 0Hz (placebo); 7Hz; 100Hz; and 255Hz. RESULTS: Both for the assessment of pressure pain threshold as the cold pain intensity, there was no significant difference (p>0.05). CONCLUSION: We conclude that the use of transcutaneous electrical nerve stimulation on dermatomes C6 to C8 produced no significant change in pressure pain threshold or cold discomfort.

Influence of different frequencies of transcutaneous electrical nerve stimulation on the threshold and pain intensity in young subjects / As influências de diferentes frequências da estimulação elétrica nervosa transcutânea no limiar e intensidade de dor em indivíduos jovens

Objective To investigate the effects of different transcutaneous electrical nerve stimulation frequencies in nociception front of a pressure pain threshold and cold in healthy individuals. Methods Twenty healthy subjects were divided into four groups, all of which have gone through all forms of electrical stimulation at different weeks. Assessments were pre and post-therapy, 20 and 60 minutes after stimulation. To evaluate the pressure pain threshold, an algometer was used with one tapered tip, pressing the hypothenar region until voluntary report the word “pain”. Cold pain intensity was assessed by immersion in water at 5°C for 30 seconds; at the end, the subject was asked to quantify the pain intensity on a Visual Analog Scale for Pain. For electrical stimulation, two electrodes were used near the elbow, for 20 minutes, with an intensity strong, but not painful. The frequency was in accordance with the group: 0Hz (placebo); 7Hz; 100Hz; and 255Hz. Results Both for the assessment of pressure pain threshold as the cold pain intensity, there was no significant difference (p>0.05). Conclusion We conclude that the use of transcutaneous electrical nerve stimulation on dermatomes C6 to C8 produced no significant change in pressure pain threshold or cold discomfort. .

Objetivo Investigar os efeitos de diferentes frequências da estimulação elétrica nervosa transcutânea na nocicepção, frente a um estímulo doloroso pressórico e ao frio, em indivíduos saudáveis. Métodos Participaram 20 indivíduos saudáveis, divididos em 4 grupos, sendo que todos passaram por todas as formas de eletroestimulação, em semanas diferentes. As avaliações ocorreram nos seguintes períodos: pré-aplicação, pós-aplicação, 20 e 60 minutos após a eletroestimulação. Para avaliar o limiar de dor à pressão, foi utilizado um algômetro com ponta afilada, pressionando na região hipotenar, até o voluntário relatar a palavra “dor”. A intensidade de dor ao frio foi avaliada por meio de imersão em água a 5°C, durante 30 segundos; ao final, pediu-se para que o indivíduo quantificasse a intensidade álgica em uma Escala Visual Analógica de Dor. Para a eletroestimulação, foram utilizados dois eletrodos próximos ao cotovelo, durante 20 minutos, com intensidade referida como forte, porém não dolorosa. A frequência esteve de acordo com o grupo: 0Hz (placebo); 7Hz; 100Hz; e 255Hz. Resultados Tanto para a avaliação do limiar de dor à pressão quanto da intensidade ao frio, não houve diferença significativa (p>0,05). Conclusão O uso da estimulação elétrica nervosa transcutânea, sobre os dermátomos de C6 a C8, não produziu alteração significativa no limiar de dor à pressão e nem no desconforto ao frio. .

Effects of taurine supplementation and swimming, associated or not, on obesity and glucose homeostasis in mice / Efeito da suplementação com taurina e da natação, associadas ou não, sobre a obesidade e homeostase glicêmica em camundongos

Studies show that physical exercise (PE) is associated with a reduced fat accumulation and increased insulin sensitivity, and taurine (TAU) improves glucose homeostasis in lean rodents. The aim in this work was evaluate the effects of supplementing TAU and practice of PE, associated or not, on obesity and glucose homeostasis on obese MSG-mice. Neonate male Swiss mice received injections of monosodium glutamate (MSG group) or saline (CON group). From the 30th to the 90th day of life, one group of animals received TAU in drinking water (MSG TAU group), another was subjected to PE (MSG PE group) and a third group underwent both procedures (MSG PE TAU group). Mice treated with MSG become obese, hypertriglyceridemic, glucose intolerant and insulin resistant. The supplementation with TAU and the PE, isolated or associated, reduced the triglycerides (38%), glucose intolerance (around 30%) and KITT (79%) in MSG-obese animals, but did not influence the accumulation of fat. Interestingly, the combination of both strategies significantly reduced the insulin resistance, compared to animals subjected to isolated strategies. In conclusion, the supplementation with TAU and PE, isolated or associated, did not influence the accumulation of fat in MSG-obese mice, however, reduce the triglycerides and insulin resistance.

O exercício físico (EF) está associado à redução do acúmulo de gordura e aumento na sensibilidade à insulina e a taurina (TAU) melhora a homeostase glicêmica em roedores magros. Objetivou-se avaliar os efeitos da suplementação com TAU e do EF, associados ou não, sobre a obesidade e a homeostase glicêmica em camundongos obesos-MSG. Camundongos Swiss machos neonatos receberam injeções de glutamato monossódico (grupo MSG) ou salina (grupo CON). Do 30º ao 90º dia de vida, um grupo de animais MSG recebeu TAU na água de beber (MSG TAU); outro foi submetido ao EF (MSG EX) e um terceiro grupo foi submetido aos dois procedimentos (MSG EX TAU). Camundongos -MSG tornaram-se obesos, hipertrigliceridêmicos, intolerantes à glicose e resistentes à insulina. A suplementação com TAU e o EF, associados ou isolados, reduziram a trigliceridemia (38%), a intolerância à glicose (30%) e o KITT (79%) nos animais obesos-MSG, porém, não influenciaram o acúmulo de gordura. A associação das duas estratégias diminui significativamente a resistência à insulina, comparado aos animais submetidos às estratégias isoladas. Conclui-se que a suplementação com TAU e o EF, associados ou isolados, não influenciam no acúmulo de gordura dos camundongos obesos-MSG, porém, diminuem a trigliceridemia e a resistência à insulina.

Decreased TNF-α gene expression in periodontal ligature in MSG-obese rats: a possible protective effect of hypothalamic obesity against periodontal disease?

The prevalence of obesity is increasing globally. There is evidence that the uncontrolled energetic metabolism in obese patients can accelerate periodontal disease. Therefore, the aim of this study was evaluate the possible relationship between hypothalamic obesity induced by neonatal treatment with MSG and experimental periodontal disease. Newborn male Wistar rats received subcutaneous injections in the cervical region, of 4g/Kg/day of body weight (BW) of MSG (MSG group) or hypertonic saline solution, 1.25/kg/day BW (control group, CTL). At 70 days of life periodontal disease was induced in these animals. After they were sacrificed, radiographic analyses of alveolar bone resorption and Tumor Necrosis Factor α (TNFα) gene expression in gingival tissue were performed. The neonatal treatment with MSG did not affect the concentration of plasma glucose and cholesterol (CHOL). However, plasma insulin, non-esterified fatty acids (NEFA) and triglycerides (TG) leves were higher in MSG compared with CTL group. The alveolar bone resorption was 44% lower in MSG-obese rats compared with CTL rats. In the presence of periodontal ligature, there was an increase in this parameter in all groups. The TNFα gene expression, an inflammatory marker, in periodontal tissue was similar in obese and CTL rats. The presence of ligature increased TNFα gene expression in both groups, but in a lower extension in MSG-obese rats. In conclusion these results suggested that hypothalamic obesity may produce a protective effect against periodontal disease, however further research is needed to understand the mechanisms involved in this process.

Taurine prevents fat deposition and ameliorates plasma lipid profile in monosodium glutamate-obese rats.

The aim of the present study was to evaluate the preventive effects of taurine (TAU) supplementation upon monosodium glutamate (MSG)-induced obesity. Rats treated during the first 5 days of life with MSG or saline were distributed into the following groups: control (CTL), CTL-treated with TAU (CTAU), MSG and MSG-supplemented with TAU (MTAU). CTAU and MTAU received 2.5% of TAU in their drinking water from 21 to 90 days of life. At the end of treatment, MSG and MTAU rats were hyperinsulinemic, glucose intolerant and insulin resistant, as judged by the HOMA index. MSG and MTAU rat islets secreted more insulin at 16.7 mM glucose compared to CTL. MSG rats also showed higher triglycerides (TG) and non-esterified fatty acids (NEFA) plasma levels, Lee Index, retroperitoneal and periepidydimal fat pads, compared with CTL, whereas plasma lipid concentrations and fat depots were lower in MTAU, compared with MSG rats. In addition, MSG rats had a higher liver TG content compared with CTL. TAU decreased liver TG content in both supplemented groups, but fat content only in MTAU rats. TAU supplementation did not change glucose homeostasis, insulin secretion and action, but reduced plasma and liver lipid levels in MSG rats.

Pancreatic islets from hypothalamic obese rats maintain K+ATP channel-dependent but not -independent pathways on glucose-induced insulin release process.

One of the main features of obesity is hyperinsulinemia, which is related to insulin oversecretion. Glucose is by far the major physiological stimulator of insulin secretion. Glucose promotes an increase in the ATP/ADP ratio, which inactivates ATP-sensitive K+ channels (K+ATP) and induces beta cell depolarization with consequent calcium influx. Increased intracellular calcium concentration triggers insulin exocytosis. K+ATP channel function is important for K+ATP channel-dependent pathways involved in glucose-stimulated insulin secretion (GSIS). However, K+ATP channel-independent pathway has been identified and it has been found that this pathway sustains GSIS. Both pathways are critical to better GSIS control. GSIS was studied in pancreatic islets from hyperinsulinemic adult obese rats obtained by monosodium L-glutamate (MSG) neonatal treatment. Islets from MSG-obese rats were more glucose responsive than control ones. Diazoxide, a drug which maintains the K+ATP channels open without interfering with cell metabolism, blocked GSIS in islets from both groups. High extracellular potassium concentration plus diazoxide was used to study an alternative to the K+ATP channel pathway; in these conditions islets from MSG-obese rats did not respond, while islets from control animals showed enhanced GSIS. Results indicate that MSG-obese rats oversecreted insulin, even though the K+ATP channel-independent pathway is impaired in their beta cells.