Effects of bezafibrate in nonalcoholic steatohepatitis model mice with monosodium glutamate-induced metabolic syndrome

Sasaki, Yoshiyuki; Shimada, Tsutomu; Iizuka, Seiichi; Suzuki, Wataru; Makihara, Hiroko; Teraoka, Ryutaro; Tsuneyama, Koichi; Hokao, Ryoji; Aburada, Masaki

doi:10.1016/j.ejphar.2011.04.051

Cited by 40 publications

(24 citation statements)

References 34 publications

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“…Of great importance, bezafibrate, recently tested in a model of obese mice induced by monosodium glutamate treatment, was demonstrated to have beneficial effects on macro-and microvesicles in hepatocytes and to reduce nonalcoholic fatty liver disease activity score [275].…”

Section: Dual or Pan Ppars Agonistsmentioning

confidence: 99%

Hepatic PPARs: Their Role in Liver Physiology, Fibrosis and Treatment

Zardi¹,

Navarini²,

Sambataro³

et al. 2013

CMC

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Abstr act: Complex molecular and cellular mechanisms are involved in the pathway of liver fibrosis. Activation and transformation of hepatic stellate cells (HSCs) are considered the two main reasons for the cause and development of liver fibrosis. The peroxisome proliferator-activated receptors (PPARs) belonging to the family of ligand-activated transcription factors play a key role in liver homeostasis, regulating adipogenesis and inhibiting fibrogenesis in HSCs. Normal transcriptional function of PPARs contributes to maintain HSCs in quiescent phase. A reduced expression of PPARs in HSCs greatly induces a progression of liver fibrosis and an increased production of collagen. Here, we discuss role and function of PPARs and we take into consideration molecular factors able to reduce PPARs activity in HSCs. Finally, although further validations are needed, we illustrate novel strategies available from in vitro and animal studies on how some PPARs-agonists have been proved effective as antifibrotic substances in liver disease.

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Section: Dual or Pan Ppars Agonistsmentioning

confidence: 99%

Hepatic PPARs: Their Role in Liver Physiology, Fibrosis and Treatment

Zardi¹,

Navarini²,

Sambataro³

et al. 2013

CMC

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“…MSG-obese mice have also been reported as a suitable model for diabetes (Nagata et al, 2006;Sasaki et al, 2009) and nonalcoholic liver steatosis (Sasaki et al, 2011;Franca et al, 2014;Fujimoto et al, 2014), conditions often treated by various drugs. Moreover, this model is used for nutritional intervention studies, such as effect of Hibiscus sabdariffa (Alarcon-Aguilar et al, 2007), red yeast rice (Fujimoto et al, 2012b), or Spirulina (Fujimoto et al, 2012a).…”

Section: Introductionmentioning

confidence: 99%

Drug-Metabolizing and Antioxidant Enzymes in Monosodium L-Glutamate Obese Mice

et al. 2014

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The prevalence of obesity is rapidly increasing across the world. Physiologic alterations associated with obesity are known to alter enzyme expression and/or activities. As drug-metabolizing and antioxidant enzymes serve as defense system against potentially toxic compounds, their modulation might have serious consequences. In this work, we studied selected antioxidant and drugmetabolizing enzymes (DME) in monosodium glutamate-mouse model of obesity. Specific activities, protein, and mRNA expressions of these enzymes in liver as well as in small intestine were compared in obese male mice and in their lean counterparts. Furthermore, expression of the NF-E2-related factor 2 (Nrf2) and its relation to obesity were tested. Obtained results showed that obesity affects expression and/or activities of some DME and antioxidant enzymes.

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“…Although PMQ has been reported to have glucose-lowering effects, the molecular targets of this compound have not been revealed and a more comprehensive analysis of its role in metabolic disorders has not been undertaken. We therefore investigated the effects of PMQ, and the mechanisms involved, on metabolic disorders, using a neonatal monosodium glutamate (MSG)-induced mouse model [23].…”

Section: Introductionmentioning

confidence: 99%

Pentamethylquercetin generates beneficial effects in monosodium glutamate-induced obese mice and C2C12 myotubes by activating AMP-activated protein kinase

Shen

Han

et al. 2012

Diabetologia

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Aims/hypothesis Pentamethylquercetin (PMQ) has recently been shown to have glucose-lowering properties. Here, we aimed to characterise the effectiveness and underlying mechanisms of PMQ for ameliorating metabolic disorders in vivo and vitro. Methods We generated a mouse model of obesity by neonatal administration of monosodium glutamate (MSG) and used it to assess the properties of PMQ as a treatment for metabolic disorders. We also investigated the possible underlying mechanisms of PMQ in the prevention of metabolic disorders. Results Compared with normal mice, MSG mice had metabolic disorders, including central obesity, hyperinsulinaemia, insulin resistance, hyperglycaemia, hyperlipidaemia, decreased phosphorylation of AMP-activated protein kinase (AMPK) and acetyl-CoA carboxylase (ACC), and downregulated levels of GLUT4 in gastrocnemius muscles. In MSG mice, PMQ treatment (5, 10, 20 mg/kg daily) reduced body weight gain, waist circumference, adipose tissue mass, serum glucose, triacylglycerol and total cholesterol, while improving insulin resistance, activating AMPK and increasing ACC phosphorylation and GLUT4 abundance. In C2C12 myotubes, PMQ (10 μmol/l) increased glucose consumption by ∼65%. PMQ treatment (1-10 μmol/l) also activated AMPK, increased ACC phosphorylation and GLUT4 abundance, and upregulated the expression of some key genes involved in fatty acid oxidation. Conclusions/interpretation These findings suggest that PMQ can ameliorate metabolic disorders at least in part via stimulation of AMPK activity.

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Effects of bezafibrate in nonalcoholic steatohepatitis model mice with monosodium glutamate-induced metabolic syndrome

Cited by 40 publications

References 34 publications

Hepatic PPARs: Their Role in Liver Physiology, Fibrosis and Treatment

Hepatic PPARs: Their Role in Liver Physiology, Fibrosis and Treatment

Drug-Metabolizing and Antioxidant Enzymes in Monosodium L-Glutamate Obese Mice

Pentamethylquercetin generates beneficial effects in monosodium glutamate-induced obese mice and C2C12 myotubes by activating AMP-activated protein kinase

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