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

Abstract

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.

Quercetin But Not Quercitrin Ameliorates Tumor Necrosis Factor-Alpha-Induced Insulin Resistance in C2C12 Skeletal Muscle Cells

“…Also, previous studies have demonstrated that quercetin could increase GLUT4 in both ob/ob mice and skeletal muscle myotubes. 28,29) And, we noticed that some study found that quercetin inhibited glucose uptake in normal adipocytes 30,31) or acutely impaired glucose metabolism in hamsters, 32) however, as quercetin may be of little value in normalglycemic animals 33) and the ways of glucose utilization remains some difference between skeletal muscle and adipose tissue, the weight of such negative results from nondiabetic animal or cells seems weakened. In addition, we did not find that the glycoside quercitrin enhanced glucose uptake in these cells (chemical structures shown in Fig.…”

Quercetin can reduce insulin resistance without decreasing adipose tissue and skeletal muscle fat accumulation

“…The mechanism of action proposed by Shen et al (2012) has not been demonstrated under in vivo conditions. Thus, in this context, the potential involvement of increased fatty acid oxidation in skeletal muscle in the reduction in insulin resistance induced by quercetin was assessed in the present study.…”

“…The authors of those studies which found positive effects of quercetin on glycemic control proposed several mechanisms to explain the beneficial effect of this polyphenol: (a) the anti-oxidative protective action on the pancreatic islets (Coskun et al 2005;Babujanarthanam et al 2010;Jeong et al 2012), (b) the increase in adiponectin circulating concentration (Wein et al 2010), (c) the inhibition of small intestine glucosidase activity , (d) the reduction in the intestinal glucose absorption mediated by GLUT2 (Kwon et al 2007), (e) the increase in glucokinase activity (Vessal et al 2003) and (f) the increase in GLUT4 transporters in skeletal muscle (Jung et al 2011;Shen et al 2012;Anhê et al 2012).…”

“…Recently, Shen et al (2012) have proposed a new mechanism to explain the improvement in insulin resistance induced by pentamethylquercetin. These authors have shown that this flavonoid increases the expression of genes involved in fatty acid oxidation, such as PPAR-a, PGC-1a, CPT-1b and ACO, in C2C12 myotubes.…”

Search for New Type of PPARγ Agonist-Like Anti-diabetic Compounds from Medicinal Plants

“…59) With regard to in vivo study, several attractive studies about antidiabetic and anti-obese effects of 25 in several animal models were reported. [60][61][62][63] The detailed mechanisms of 24 and 25 are still unclear, because many transcriptional factors are involved in agipogenesis. For example, early adipogenic transcription factors [e.g.…”