Baicalin against obesity and insulin resistance through activation of AKT/AS160/GLUT4 pathway

https://doi.org/10.1016/j.mce.2017.03.027Get rights and content

Highlights

  • I.p injection of baicalin decreases body weight and food intake of obese mice.

  • I.p injection of baicalin reduces blood glucose concentration and insulin resistance.

  • I.p injection of baicalin increases GLUT4 expression levels in skeletal muscle.

  • I.p injection of baicalin improves GLUT4 translocation level in skeletal muscle.

  • Baicalin attenuates skeletal muscle insulin resistance via the Akt/AS160/GLUT4 pathway.

Abstract

Obesity may cause several metabolic complications, including insulin resistance and type 2 diabetes mellitus. Despite great advances in medicine, people still keep exploring novel and effective drugs for treatment of obesity and insulin resistance. The aim of this study was to survey if baicalin might ameliorate obesity-induced insulin resistance and to explore its signal mechanisms in skeletal muscles of mice. Diet-induced obese (DIO) mice were given 50 mg/kg baicalin intraperitoneally (i.p.) once a day for 21 days, and C2C12 myotubes were treated with 100, 200, 400 μM baicalin for 12 h in this study. Then insulin resistance indexes and insulin signal protein levels in skeletal muscles were examined. We discovered that administration of baicalin decreased food intake, body weight, HOMA-IR and NT-PGC-1α levels, but enhanced GLUT4, PGC-1α, pP38MAPK, pAKT and pAS160 contents, as well as GLUT4 mRNA, PGC-1α mRNA, PPARγ mRNA, GLUT1 mRNA expression in skeletal muscles of obese mice and myotubes of C2C12 cells, and reversed high fat diet-induced glucose and insulin intolerance, hyperglycemia and insulin resistance in the mice. These results suggest that baicalin is a powerful and promising agent for treatment of obesity and insulin resistance via Akt/AS160/GLUT4 and P38MAPK/PGC1α/GLUT4 pathway.

Introduction

Obesity is an identified risk factor for developing insulin resistance and type 2 diabetes mellitus (Fang et al., 2012; Liu et al., 2009, Lazar, 2005). In obese subjects, chronic inflammation arises in adipose tissue, resulting in increased adipokine secretion and decreased glucose transporter 4 (GLUT4) expression and translocation in skeletal muscles and adipose tissues, which are an early step to develop insulin resistance and type 2 diabetes (Saltiel and Kahn, 2001).

Herbal medicines are characterized by comprehensive regulation of body homeostasis through multiple components existing together in a prescription. It is attractive to explore new medicines with less expenditure and side effects from Herbal extracts than synthetic hypoglycemic agents for treatment of insulin resistance. Scutellaria baicalensis Georgi (known as huáng qín) is a traditional Chinese herb, exhibiting antioxidant, anti-inflammatory, antidiabetic and antidyslipidemic properties (de Oliveira et al., 2015, Xi et al., 2015). Baicalin is one of the most potent and abundant polyphenolic extracts from Scutellaria baicalensis (Li and Chen, 2005). A few studies reported that baicalin possesses the anti-obesity characteristic via inhibition of adipogenesis in 3T3-L1 preadipocytes, and prevention of dyslipidemia to decrease epididymal fat, hyperlipidemia, liver steatosis and body weights in murinae fed with high fat diet (Lee et al., 2009, Yang et al., 2016, Zhu et al., 2016, Xi et al., 2015, Xi et al., 2016). Besides, baicalin was reported to have hepatoprotective effects through the Ca2+/CaM-dependent protein kinase β (CaMKKβ)/AMP-activated protein kinase (AMPKα)/acetyl-CoA carboxylase (ACC) pathway in liver (Xi et al., 2015). However, the ameliorative effect of baicalin on insulin resistance has not been sufficiently explored in mice fed high-fat diet. The primary aim of this study was to investigate whether baicalin could attenuate obesity-induced insulin resistance and what is the relative signal pathway in skeletal muscles of mice and C2C12 myotubes.

Section snippets

Drugs and reagents

Baicalin and 2-[N-(7-nitrobenz-2-oxa-1, 3-diazol-4-yl) amino]-2-deoxy-D-glucose (2-NBDG) were purchased from Sigma-Aldrich, USA. Antibodies against P38MAPK, pP38MAPK, Akt, pAkt, AS160 and pAS160 were acquired from Cell Signaling Technology Inc, USA. Antibodies against GLUT4, peroxisome proliferator-activated receptor-γ coactivator-1α (PGC-1α) and its splice variant N terminal (NT)-PGC-1α (NT-PGC-1α) from Merck Millipore Inc, Germany. Antibodies against glyceraldehyde-phosphate dehydrogenase

Body weight and food intake

All of the six-week-old mice used in this experiment exhibited similar body weight and food intake at the beginning of the experiment. Feeding of a high fat diet for 16 weeks enhanced body weight of the mice in obese control and baicalin groups compared with the normal diet group before the administration of baicalin (Fig. 1). As shown in Fig. 1, Fig. 2 the body weight and delta weight at 21 days were significantly decreased by 33.9% (P < 0.01) and 423.94% (P < 0.001) in the baicalin group

Discussion

Baicalin is a bioactive flavonoid isolated from the radix of Scutellaria baicalensis, which contains several bioactive compounds, such as baicalein, baicalin, β-sitosterol, norwogonin, oroxylin A, and wogonin (Li and Chen, 2005, de Oliveira et al., 2015). Recent research indicated that administration of baicalin could alleviate obesity, hyperglycemia and insulin resistance.

First, a few studies reported that baicalin might play an anti-obesity role (Lee et al., 2009, Xi et al., 2015, Yang

Competing interests

The authors declared no conflict of interest.

Acknowledgments

This work was supported by the National Natural Scientific Fund of China (No. 81673736) and in part by the National Health and Family Planning Commission of China (Grant No. W201309).

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