Association between protein undernutrition and diabetes: Molecular implications in the reduction of insulin secretion.

Undernutrition is still a recurring nutritional problem in low and middle-income countries. It is directly associated with the social and economic sphere, but it can also negatively impact the health of the population. In this sense, it is believed that undernourished individuals may be more susceptible to the development of non-communicable diseases, such as diabetes mellitus, throughout life. This hypothesis was postulated and confirmed until today by several studies that demonstrate that experimental models submitted to protein undernutrition present alterations in glycemic homeostasis linked, in part, to the reduction of insulin secretion. Therefore, understanding the changes that lead to a reduction in the secretion of this hormone is essential to prevent the development of diabetes in undernourished individuals. This narrative review aims to describe the main molecular changes already characterized in pancreatic ß cells that will contribute to the reduction of insulin secretion in protein undernutrition. So, it will provide new perspectives and targets for postulation and action of therapeutic strategies to improve glycemic homeostasis during this nutritional deficiency.

Sleeve Gastrectomy-Induced Weight Loss Increases Insulin Clearance in Obese Mice.

Sleeve gastrectomy (SG) successfully recovers metabolic homeostasis in obese humans and rodents while also resulting in the normalization of insulin sensitivity and insulinemia. Reduced insulin levels have been attributed to lower insulin secretion and increased insulin clearance in individuals submitted to SG. Insulin degradation mainly occurs in the liver in a process controlled, at least in part, by the insulin-degrading enzyme (IDE). However, research has yet to explore whether liver IDE expression or activity is altered after SG surgery. In this study, C57BL/6 mice were fed a chow (CTL) or high-fat diet (HFD) for 10 weeks. Afterward, the HFD mice were randomly assigned to two groups: sham-surgical (HFD-SHAM) and SG-surgical (HFD-SG). Here, we confirmed that SG improves glucose-insulin homeostasis in obese mice. Additionally, SG reduced insulinemia by reducing insulin secretion, assessed by the analysis of plasmatic C-peptide content, and increasing insulin clearance, which was evaluated through the calculation of the plasmatic C-peptide:insulin ratio. Although no changes in hepatic IDE activity were observed, IDE expression was higher in the liver of HFD-SG compared with HFD-SHAM mice. These results indicate that SG may be helpful to counteract obesity-induced hyperinsulinemia by increasing insulin clearance, likely through enhanced liver IDE expression.

The Taurine-Conjugated Bile Acid (TUDCA) Normalizes Insulin Secretion in Pancreatic ß-Cells Exposed to Fatty Acids: The Role of Mitochondrial Metabolism.

Bile acid tauroursodeoxycholic (TUDCA), formed from the association of ursodeoxycholic acid (UDCA) with taurine, has already been shown to increase mitochondrial biogenesis and cell survival, in addition to reduce reticulum stress markers in different cell types. However, its mechanism of action upon insulin secretion control in obesity is still unknown. In this sense, we seek to clarify whether taurine, associated with bile acid, could improve the function of the pancreatic ß-cells exposed to fatty acids through the regulation of mitochondrial metabolism. To test this idea, insulin-producing cells (INS1-E) were exposed to a fatty acid mix containing 500 µM of each palmitate and oleate for 48 hours treated or not with 300 µM of TUDCA. After that, glucose-stimulated insulin secretion and markers of mitochondrial metabolism were evaluated. Our results showed that the fatty acid mix was efficient in inducing hyperfunction of INS1-E cells as observed by the increase in insulin secretion, protein expression of citrate synthase, and mitochondrial density, without altering cell viability. The treatment with TUDCA normalized insulin secretion, reducing the protein expression of citrate synthase, mitochondrial mass, and the mitochondrial membrane potential. This effect was associated with a decrease in the generation of mitochondrial superoxide and c-Jun N-terminal kinase (JNK) protein content. The findings are also consistent with the hypothesis that TUDCA normalizes insulin secretion by improving mitochondrial metabolism and redox balance. Thus, it highlights likely mechanisms of the action of this bile acid on the glycemic homeostasis reestablishment in obesity.

Dietary Protein Modulates the Efficacy of Taurine Supplementation on Adaptive Islet Function and Morphology in Obesity.

Adaptation of islet ß-cell mass and function under limiting or excess nutrient availability is critical for maintenance of glucose homeostasis. Taurine regulates islet function of obese mice in normal and low dietary protein conditions, but whether this involves remodeling of the endocrine pancreas architecture is not well understood. Here, we carried functional and morphometric evaluation of the endocrine pancreas of normal and protein-restricted mice fed a high-fat diet (HFD) and investigated the role of taurine supplementation. Weaned mice were placed in a normal (C) or a low-protein diet (R) for 6 weeks, followed by HFD for 8 weeks (CH and RH). Half of HFD groups received 5% taurine supplementation since weaning (CHT and RHT) until the end of the experiment. Isolated islets from both CH and RH groups showed increased insulin release in association with increased pancreas weight and independently of changes in islet or ß-cell area. In normal protein CHT mice, taurine supplementation prevented obesity-induced insulin hypersecretion and promoted increased islet and ß-cell areas in association with increased protein expression of the proliferation marker, PCNA. On a low-protein background, taurine effects on islet function and morphology were blunted, but it prevented obesity-induced DNA fragmentation. In summary, taurine regulates islet function and morphology to improve the adaptive response to diet-induced obesity, but these effects are dependent on adequate dietary protein levels.

Protein malnutrition early in life increased apoptosis but did not alter the ß-cell mass during gestation.

We evaluated whether early-life protein restriction alters structural parameters that affect ß-cell mass on the 15th day and 20th day of gestation in control pregnant (CP), control non-pregnant (CNP), low-protein pregnant (LPP) and low-protein non-pregnant (LPNP) rats from the fetal to the adult life stage as well as in protein-restricted rats that recovered after weaning (recovered pregnant (RP) and recovered non-pregnant). On the 15th day of gestation, the CNP group had a higher proportion of smaller islets, whereas the CP group exhibited a higher proportion of islets larger than the median. The ß-cell mass was lower in the low-protein group than that in the recovered and control groups. Gestation increased the ß-cell mass, ß-cell proliferation frequency and neogenesis frequency independently of the nutritional status. The apoptosis frequency was increased in the recovered groups compared with that in the other groups. On the 20th day of gestation, a higher proportion of islets smaller than the median was observed in the non-pregnant groups, whereas a higher proportion of islets larger than the median was observed in the RP, LPP and CP groups. ß-Cell mass was lower in the low-protein group than that in the recovered and control groups, regardless of the physiological status. The ß-cell proliferation frequency was lower, whereas the apoptosis rate was higher in recovered rats compared with those in the low-protein and control rats. Thus, protein malnutrition early in life did not alter the mass of ß-cells, especially in the first two-thirds of gestation, despite the increase in apoptosis.

Amino acid restriction alters survival mechanisms in pancreatic beta cells: possible role of the PI3K/Akt pathway.

BACKGROUND AND AIMS: Malnutrition in the early stages of life may lead to changes in the glycemic metabolism during adulthood, such as pancreatic beta cells dysfunction and failure. Therefore, this study aimed to evaluate the effects of an in vitro amino acid restriction model on the function and viability of pancreatic beta cells. METHODS: Insulin-producing cells (INS-1E) were maintained in control or amino acid restricted culture medium containing 1 × or 0.25 × of amino acids, respectively, for 48 h. RESULTS: Amino acid restricted group showed lower insulin secretion and insulin gene expression, reduced mitochondrial oxygen consumption rate and reactive oxygen species production. Besides, amino acid restricted group also showed higher levels of endoplasmic reticulum stress and apoptosis markers and enhanced Akt phosphorylation. However, even with higher levels of apoptosis markers, amino acid restricted group did not show higher levels of cell death unless the PI3K/Akt pathway was inhibited. CONCLUSION: Amino acid restricted beta cell viability seems to be dependent on the PI3K/Akt pathway.

Regulation of Lin28a-miRNA let-7b-5p pathway in skeletal muscle cells by peroxisome proliferator-activated receptor delta.

Lin28a/miRNA let-7b-5p pathway has emerged as a key regulators of energy homeostasis in the skeletal muscle. However, the mechanism through which this pathway is regulated in the skeletal muscle has remained unclear. We have found that 8 wk of aerobic training (Tr) markedly decreased let-7b-5p expression in murine skeletal muscle, whereas high-fat diet (Hfd) increased its expression. Conversely, Lin28a expression, a well-known inhibitor of let-7b-5p, was induced by Tr and decreased by Hfd. Similarly, in human muscle biopsies, Tr increased LIN28 expression and decreased let-7b-5p expression. Bioinformatics analysis of LIN28a DNA sequence revealed that its enrichment in peroxisome proliferator-activated receptor delta (PPARδ) binding sites, which is a well-known metabolic regulator of exercise. Treatment of primary mouse skeletal muscle cells or C2C12 cells with PPARδ activators GW501516 and AICAR increased Lin28a expression. Lin28a and let-7b-5p expression was also regulated by PPARδ coregulators. While PPARγ coactivator-1α (PGC1α) increased Lin28a expression, corepressor NCoR1 decreased its expression. Furthermore, PGC1α markedly reduced the let-7b-5p expression. PGC1α-mediated induction of Lin28a expression was blocked by the PPARδ inhibitor GSK0660. In agreement, Lin28a expression was downregulated in PPARδ knocked-down cells leading to increased let-7b-5p expression. Finally, we show that modulation of the Lin28a-let-7b-5p pathway in muscle cells leads to changes in mitochondrial metabolism in PGC1α dependent fashion. In summary, we demonstrate that Lin28a-let-7b-5p is a direct target of PPARδ in the skeletal muscle, where it impacts mitochondrial respiration.

Early protein restriction increases intra-islet GLP-1 production and pancreatic ß-cell proliferation mediated by the ß-catenin pathway.

PURPOSE: In the present study, we investigated whether intra-islet GLP-1 production and its modulation have a role in apoptosis, proliferation or neogenesis that is compromised by protein restriction during the foetal and suckling periods. METHODS: Exendin-4, a GLP-1 receptor agonist (treated groups), or saline (non-treated groups) was intraperitoneally administered for 15 days from 75 to 90 days of age in female adult rats consisting of offspring born to and suckled by mothers fed a control diet (control groups) and who had the same diet until 90 days of age or offspring born to and suckled by mothers fed a low-protein diet and who were fed the control diet after weaning until 90 days of age (protein-restricted group). RESULTS: The ß-cell mass was lower in the protein-restricted groups than in the control groups. Exendin-4 increased ß-cell mass, regardless of the mother's protein intake. The colocalization of GLP-1/glucagon was higher in the protein-restricted rats than in control rats in both the exendin-4-treated and non-treated groups. The frequency of cleaved caspase-3-labelled cells was higher in the non-treated protein-restricted group than in the non-treated control group and was similar in the treated protein-restricted and treated control groups. Regardless of treatment with exendin-4, Ki67-labelled cell frequency and ß-catenin/DAPI colocalization were elevated in the protein-restricted groups. Exendin-4 increased the area of endocrine cell clusters and ß-catenin/DAPI and FoxO1/DAPI colocalization regardless of the mother's protein intake. CONCLUSIONS: Protein restriction in early life increased intra-islet GLP-1 production and ß-cell proliferation, possibly mediated by the ß-catenin pathway.

The use of the "Endocrine Circuit" as an active learning methodology to aid in the understanding of the human endocrine system.

The search for more efficient teaching methodologies is a great challenge for Brazilian educators, since most classes are still traditional (theoretical) and have little student involvement during the learning process. Active learning methodologies, where students play a central role in the learning process, are proving to be more effective and interesting when it comes to acquiring knowledge. Thus we decided to develop an innovative technique for teaching Human Endocrine Physiology, called "Endocrine Circuit." The circuit consisted of eight stations in which students were asked to organize a scheme with cards to answer a specific question about a gland or tissue with endocrine relevance. The effectiveness of the developed activity was validated through a pretest-posttest design, in which the students had to answer a 10-question test. We found out that, after the Endocrine Circuit application, students showed an improvement in the percentage of correct answers for 7 out of 10 questions contained in the questionnaire (P ≤ 0.05). In addition, the activity showed positive outcomes regarding student's engagement in this study, besides showing to be more efficient than the Brazilian traditional theoretical classes.

Hypoglycaemic effect of resveratrol in streptozotocin-induced diabetic rats is impaired when supplemented in association with leucine.

Studies have shown synergistic and independent effects of leucine and resveratrol (RSV) as possible therapeutic agents to ameliorate metabolic disorders. Thus, the objective of this study was to investigate the effects of supplementation with leucine and RSV, alone and in combination, on metabolic changes in white adipose tissue of neonatally STZ-induced diabetic rats. After weaning, the rats were treated with trans-resveratrol (0.6 mg/kg/dose) and/or leucine (1.35 mg/kg/dose) administered orally. The animals were euthanized at age 16 weeks for blood analyses. Subcutaneous (SC), periepididymal (PE) and retroperitoneal (RP) fat pads were weighed. Adipocytes from PE and RP pads were isolated for morphometric analysis. Long-term supplementation with RSV promoted adiposity recovery, prevented hypoinsulinemia and improved the metabolic profile of the diabetic rats. However, some of these effects were impaired when RSV was associated with leucine. The diabetic rats supplemented with leucine alone showed no significant improvement in metabolic disorders.

Amino acid restriction increases ß-cell death under challenging conditions.

Malnutrition programs metabolism, favor dysfunction of ß cells. We aimed to establish an in vitro protocol of malnutrition, assessing the effect of amino acid restriction upon the ß cells. Insulin-producing cells INS-1E and pancreatic islets were maintained in RPMI 1640 medium containing 1× (Ctl) or 0.25× (AaR) of amino acids. We evaluated several markers of ß-cell function and viability. AaR Insulin secretion was reduced, whereas cell viability was unaltered. Calcium oscillations in response to glucose increased in AaR. AaR showed lower Ins1 RNAm, snap 25, and PKC (protein kinase C) protein content, whereas phospho-eIF2α was increased. AaR cells exposed to nutrient or chemical challenges displayed higher apoptosis rates. We showed that amino acid restriction programmed ß cell and induced functional changes. This model might be useful for the study of molecular mechanisms involved with ß-cell programming helping to establish novel therapeutic targets to prevent harmful outcomes of malnutrition.

Protein malnutrition mitigates the effects of a high-fat diet on glucose homeostasis in mice.

Nutrient malnutrition, during the early stages of development, may facilitate the onset of metabolic diseases later in life. However, the consequences of nutritional insults, such as a high-fat diet (HFD) after protein restriction, are still controversial. We assessed overall glucose homeostasis and molecular markers of mitochondrial function in the gastrocnemius muscle of protein-restricted mice fed an HFD until early adulthood. Male C57BL/6 mice were fed a control (14% protein-control diet) or a protein-restricted (6% protein-restricted diet) diet for 6 weeks. Afterward, mice received an HFD or not for 8 weeks (mice fed a control diet and HFD [CH] and mice fed a protein-restricted diet and HFD [RH]). RH mice showed lower weight gain and fat accumulation and did not show an increase in fasting plasma glucose and insulin levels compared with CH mice. RH mice showed higher energy expenditure, increased citrate synthase, peroxisome-proliferator-activated receptor gamma coactivator 1-alpha protein content, and higher levels of malate and α-ketoglutarate compared with CH mice. Moreover, RH mice showed increased AMPc-dependent kinase and acetyl coenzyme-A (CoA) carboxylase phosphorylation, lower intramuscular triacylglycerol content, and similar malonyl-CoA levels. In conclusion, protein undernourishment after weaning does not potentiate fat accumulation and insulin resistance in adult young mice fed an HFD. This outcome seems to be associated with increased skeletal muscle mitochondrial oxidative capacity and reduced lipids accumulation.

Protein restriction in early life increases intracellular calcium and insulin secretion, but does not alter expression of SNARE proteins during pregnancy.

NEW FINDINGS: What is the central question of this study? Does protein restriction in early life modify glucose-induced insulin secretion by altering [Ca2+ ]i and the expression of SNARE proteins in pancreatic islets from pregnant rats? What is the main finding and its importance? Protein restriction in early life increased the first phase of glucose-induced insulin secretion and [Ca2+ ]i without altering the expression of SNARE proteins during pregnancy. This finding contributes to our understanding of the mechanisms of altered insulin secretion and might provide new perspectives for the development of therapeutic tools for gestational diabetes. ABSTRACT: We investigated the kinetics of glucose-induced insulin secretion and their relationship with [Ca2+ ]i and the expression of protein from exocytotic machinery in islets from recovered pregnant and long-term protein-deficient pregnant rats. Isolated islets were evaluated from control-fed pregnant (CP), protein-deficient pregnant (DP), control-fed non-pregnant (CNP) and protein-deficient non-pregnant (DNP) female adult rats, and from protein-deficient pregnant (RP) and non-pregnant (RNP) rats that were recovered after weaning. The insulin responses to glucose during the first phase of secretion were higher in RP than in CP groups, and both were higher than in the DP group. Islets from RP rats displayed a rapid increase in insulin release (first phase), followed by a plateau that was maintained thereafter. The [Ca2+ ]i in islets from the protein-deficient groups was lower than in the control groups, and both were lower than in the RP and RNP groups. SNAP-25 was increased in islets from pregnant rats independently of their nutritional status, and the syntaxin-1A content was reduced in islets from the RP rats compared with the RNP rats. The VAMP2 content was similar among the groups. Thus, protein restriction during intrauterine life and lactation increased insulin secretion during pregnancy, attributable, in part, to increased [Ca2+ ]i , and independent of an alteration of expression of SNARE proteins.

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.

ARHGAP21 deficiency impairs hepatic lipid metabolism and improves insulin signaling in lean and obese mice.

ARHGAP21 is a Rho-GAP that controls GTPases activity in several tissues, but its role on liver lipid metabolism is unknown. Thus, to achieve the Rho-GAP role in the liver, control and ARHGAP21-haplodeficient mice were fed chow (Ctl and Het) or high-fat diet (Ctl-HFD and Het-HFD) for 12 weeks, and pyruvate and insulin tolerance tests, insulin signaling, liver glycogen and triglycerides content, gene and protein expression, and very-low-density lipoprotein secretion were measured. Het mice displayed reduced body weight and plasma triglycerides levels, and increased liver insulin signaling. Reduced gluconeogenesis and increased glycogen content were observed in Het-HFD mice. Gene and protein expression of microsomal triglyceride transfer protein were reduced in both Het mice, while the lipogenic genes SREBP-1c and ACC were increased. ARHGAP21 knockdown resulted in hepatic steatosis through increased hepatic lipogenesis activity coupled with decreases in CPT1a expression and very-low-density lipoprotein export. In conclusion, liver of ARHGAP21-haplodeficient mice are more insulin sensitive, associated with higher lipid synthesis and lower lipid export.

Protein malnutrition blunts the increment of taurine transporter expression by a high-fat diet and impairs taurine reestablishment of insulin secretion.

Taurine (Tau) restores ß-cell function in obesity; however, its action is lost in malnourished obese rodents. Here, we investigated the mechanisms involved in the lack of effects of Tau in this model. C57BL/6 mice were fed a control diet (CD) (14% protein) or a protein-restricted diet (RD) (6% protein) for 6 wk. Afterward, mice received a high-fat diet (HFD) for 8 wk [CD + HFD (CH) and RD + HFD (RH)] with or without 5% Tau supplementation after weaning on their drinking water [CH + Tau (CHT) and RH + Tau (RHT)]. The HFD increased insulin secretion through mitochondrial metabolism in CH and RH. Tau prevented all those alterations in CHT only. The expression of the taurine transporter (Tau-T), as well as Tau content in pancreatic islets, was increased in CH but had no effect on RH. Protein malnutrition programs ß cells and impairs Tau-induced restoration of mitochondrial metabolism and biogenesis. This may be associated with modulation of the expression of Tau-T in pancreatic islets, which may be responsible for the absence of effect of Tau in protein-malnourished obese mice.-Branco, R. C. S., Camargo, R. L., Batista, T. M., Vettorazzi, J. F., Borck, P. C., dos Santos-Silva, J. C. R., Boschero, A. C., Zoppi, C. C., Carneiro, E. M. Protein malnutrition blunts the increment of taurine transporter expression by a high-fat diet and impairs taurine reestablishment of insulin secretion.

Taurine supplementation induces long-term beneficial effects on glucose homeostasis in ob/ob mice.

The sulfur-containing amino acid, taurine (Tau), regulates glucose and lipid homeostasis under normal, pre- and diabetic conditions. Here, we aimed to verify whether Tau supplementation exerts its beneficial effects against obesity, hyperglycemia and alterations in islet functions, in leptin-deficient obese (ob/ob), over a long period of treatment. From weaning until 12 months of age, female ob/ob mice received, or not, 5% Tau in drinking water (obTau group). After this period, a reduction in hypertriglyceridemia and an improvement in glucose tolerance and insulin sensitivity were observed in obTau mice. In addition, the daily metabolic flexibility was restored in obTau mice. In the gastrocnemius muscle of obTau mice, the activation of AMP-activated protein kinase (AMPK) was increased, while total AMPK protein content was reduced. Finally, isolated islets from obTau mice expressed high amounts of pyruvate carboxylase (PC) protein and lower glucose-induced insulin secretion. Taking these evidences together Tau supplementation had long-term positive actions on glucose tolerance and insulin sensitivity, associated with a reduction in glucose-stimulated insulin secretion, in ob/ob mice. The improvement in insulin actions in obTau mice was due, at least in part, to increased activation of AMPK in skeletal muscle, while the increased content of the PC enzyme in pancreatic islets may help to preserve glucose responsiveness in obTau islets, possibly contributing to islet cell survive.

miR-124a expression contributes to the monophasic pattern of insulin secretion in islets from pregnant rats submitted to a low-protein diet.

PURPOSE: To evaluate the role of miR-124a in the regulation of genes involved in insulin exocytosis and its effects on the kinetics of insulin secretion in pancreatic islets from pregnant rats submitted to a low-protein diet. METHODS: Adult control non-pregnant (CNP) and control pregnant (CP) rats were fed a normal protein diet (17%), whereas low-protein non-pregnant (LPNP) and low-protein pregnant (LPP) rats were fed a low-protein diet (6%) from days 1 to 15 of pregnancy. Kinetics of the glucose-induced insulin release and measurement of [Ca2+]i in pancreatic islets were assessed by standard protocols. The miR-124a expression and gene transcriptions from pancreatic islets were determined by real-time polymerase chain reaction. RESULTS: In islets from LPP rats, the first phase of insulin release was abrogated. The AUC [Ca2+]i from the LPP group was lower compared with the other groups. miR-124a expression was reduced by a low-protein diet. SNAP-25 mRNA, protein expression, and Rab3A protein content were lower in the LPP rats than in CP rats. Syntaxin 1A and Kir6.2 mRNA levels were decreased in islets from low-protein rats compared with control rats, whereas their protein content was reduced in islets from pregnant rats. CONCLUSIONS: Loss of biphasic insulin secretion in islets from LPP rats appears to have resulted from reduced [Ca2+]i due, at least in part, to Kir6.2 underexpression and from the changes in exocytotic elements that are influenced either directly or indirectly by miR-124a.

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.