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