Mechanisms underlying hypertriglyceridemia in rats with monosodium l-glutamate-induced obesity: Evidence of XBP-1/PDI/MTP axis activation

França, Lucas Martins; Freitas, Larissa Nara Costa; Chagas, Vinicyus Teles; Coêlho, Caio Fernando Ferreira; Barroso, Wermerson Assunção; Costa, Graciomar C.; Silva, Lucilene Amorim; Debbas, Victor; Laurindo, Francisco Rafael Martins

doi:10.1016/j.bbrc.2013.12.042

Cited by 24 publications

(20 citation statements)

References 30 publications

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“…Figure 3 presents the obtained results of determining TNFα cytokine secretion. It can be observed a uniform decrease of TNFα secretion for exposure of RAW cells in more concentrated MSG solutions (higher than 25 mM MSG), a fact which is apparently contrary with some literature data [29][30][31][32][33][34][35][36] that indicated an increases of this cytokine levels following MSG intake. Our explanation consists in the particularity that nitric oxide downregulates tumor necrosis factor mRNA in RAW 264.7 cells, acting mainly by reducing its half-life time [37] and it was thus proven the existence of a negative feedback by endogenous NO oxide on TNF in vitro synthesis [25].…”

Section: Msg-induced Cytotoxicity Measured By Testing the Degree Of Ocontrasting

confidence: 88%

In vitro Evaluation of the Antiproliferative Effect, Cytotoxicity and Proinflammatory Activity of the Food Additive Monosodium Glutamate on RAW 264.7 Cell Line

Baciu¹,

Sălăgeanu²,

Visan³

2020

Rev. Chim.

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Monosodium glutamate (E-621, abbreviated MSG) is a food additive widely used in the food domain as a flavor and taste enhancer. The present study aims to evaluate in vitro the effects of increased concentrations of MSG, using the RAW 264.7 murine macrophage line. The study was conducted in 3 complementary directions: first, establishing the ability of monosodium glutamate to induce cell mortality, by using the MTT assay to determine cell viability; second, establishing by its oxidizing activity if MSG is toxic for cells inducing oxidative stress, measured by the Griess test for determination of extracellular NO; third, to observe whether MSG presence induces an immune response quantified by the secretion of proinflammatory cytokines, TNFα in this case, measured through the immunoenzymatic ELISA technique.

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Section: Msg-induced Cytotoxicity Measured By Testing the Degree Of Ocontrasting

confidence: 88%

In vitro Evaluation of the Antiproliferative Effect, Cytotoxicity and Proinflammatory Activity of the Food Additive Monosodium Glutamate on RAW 264.7 Cell Line

Baciu¹,

Sălăgeanu²,

Visan³

2020

Rev. Chim.

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“…It is generally accepted that the IRE1α/XBP-1 pathway contributes to organized folding and degradation of proteins in the ER [14]. Although XBP-1 is crucial for cellular development and the survival of several types of malignant cells, its role differs depending on the organ and cell type in which it is found among other conditions [15–18]. A recent study suggested that during FFA elevation in serum, ER stress response may be directly activated by membrane lipid saturation and not only by unfolded proteins [19].…”

Section: Introductionmentioning

confidence: 99%

Toyocamycin attenuates free fatty acid-induced hepatic steatosis and apoptosis in cultured hepatocytes and ameliorates nonalcoholic fatty liver disease in mice

et al. 2017

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Background and aimsA high serum level of saturated free fatty acids (FFAs) is associated with the development of nonalcoholic fatty liver disease (NAFLD). X-box binding protein-1 (XBP-1) is activated by FFA treatment upon splicing. XBP-1 is a transcription factor induced by the endoplasmic reticulum (ER) stress sensor endoribonuclease inositol-requiring enzyme 1 alpha (IRE1α). However, the role of XBP-1 in NAFLD remains relatively unexplored. Toyocamycin was recently reported to attenuate the activation of XBP-1, possibly by inducing a conformational change in IRE1α. In this study, we examined the effect of toyocamycin on hepatocyte lipoapoptosis and steatosis. We also explored the effects of toyocamycin in a mouse model of NAFLD.MethodsHuh-7 cells and isolated rat primary hepatocytes were treated with palmitic acid (PA), which is a saturated FFA, in the presence or absence of toyocamycin. In addition, male C57BL/6J mice were fed a diet rich in saturated fat, fructose, and cholesterol (FFC) for 4 months, after which the effect of toyocamycin was assessed.ResultsToyocamycin attenuated FFA-induced steatosis. It also significantly reduced PA-induced hepatocyte lipoapoptosis. In addition, toyocamycin reduced the expression of cytosine-cytosine-adenosine-adenosine-thymidine enhancer-binding protein homologous protein (CHOP), which is a key player in ER stress-mediated apoptosis, as well as its downstream cell death modulator, death receptor 5. In the in vivo study, toyocamycin ameliorated the liver injury caused by FFC-induced NAFLD. It also reduced hepatic steatosis and the expression of lipogenic genes.ConclusionsThe data we obtained suggest that toyocamycin attenuates hepatocyte lipogenesis and ameliorates NAFLD in vivo and may therefore be beneficial in the treatment of NAFLD in humans.

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“…In a previous study, we showed that 16-week-old MSG rats had NAFLD associated to hypertriglyceridemia. 21 Moreover, it is well documented that 24-week-old MSG mice acquire acute NASH with human histopathologic features, 22 which evolved into cirrhosis around 54 weeks old. 17 Other studies have also described NAFLD-to-NASH development in MSG mice, but generally in adult to middle-aged animals.…”

Section: Introductionmentioning

confidence: 99%

Early onset and progression of non-alcoholic fatty liver disease in young monosodium l-glutamate-induced obese mice

Coêlho

França

Nascimento

et al. 2018

J Dev Orig Health Dis

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Monosodium l-glutamate (MSG)-induced obesity is a useful model for non-alcoholic fatty liver disease (NAFLD) studies. However, there is limited data on its initiation and progression. Thus, this study aimed to characterize the onset of metabolic and histopathological features of NAFLD and its progression to non-alcoholic steatohepatitis (NASH) in this model. To perform this study, Swiss mice pups were neonatally injected with MSG (4 g/kg/day, s.c.) or equiosmolar saline and followed up to 60, 120 or 180 days old. At each age, blood, liver, as well as periepididymal and retroperitoneal fat pads were collected for morphometric, biochemical and histological analyses, the later according to NAFLD activity score. MSG mice presented hypertriglyceridemia and central obesity at all ages, but peripheral insulin-resistance was verified only in 120- and 180-day-old mice. Hepatic total fat and triglycerides content were higher in MSG mice at all ages. Accordingly, histopathological analysis showed that 60-day-old MSG mice had microvesicular steatosis with occasional ballooning, which evolved into NASH from 120 days old. Retroperitoneal fat accumulation was the only variable to independently correlate with NAFLD activity total score upon multivariate analysis (R 2=71.45%). There were no differences in IL-6 and TNF-α serum levels among groups. Overall, this study shows that NAFLD is a precocious outcome in MSG-obese mice, whereas the period comprised between 60 and 120 days old seems to be a crucial metabolic window for comprehending pathophysiological events involved in NAFLD-to-NASH progression in this model.

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Mechanisms underlying hypertriglyceridemia in rats with monosodium l-glutamate-induced obesity: Evidence of XBP-1/PDI/MTP axis activation

Cited by 24 publications

References 30 publications

In vitro Evaluation of the Antiproliferative Effect, Cytotoxicity and Proinflammatory Activity of the Food Additive Monosodium Glutamate on RAW 264.7 Cell Line

In vitro Evaluation of the Antiproliferative Effect, Cytotoxicity and Proinflammatory Activity of the Food Additive Monosodium Glutamate on RAW 264.7 Cell Line

Toyocamycin attenuates free fatty acid-induced hepatic steatosis and apoptosis in cultured hepatocytes and ameliorates nonalcoholic fatty liver disease in mice

Early onset and progression of non-alcoholic fatty liver disease in young monosodium l-glutamate-induced obese mice

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