This study was undertaken to examine the effect and mechanism of
Bofu-tsusho-san formula (BO) on
hyperglycemia and
hyperlipidemia and in mice fed with a high-fat (HF) diet. The C57BL/6J mice were received control/HF diet for 12 weeks, and
oral administration of BO (at three doses) or
rosiglitazone (Rosi) or vehicle for the last 4 weeks. Blood, skeletal muscle and tissues were examined by means of measuring glycaemia and dyslipidaemia-associated events. BO treatment effectively prevented HF diet-induced increases in the levels of
triglyceride (TG),
free fatty acid (FFA) and
leptin (p<0.01, p<0.01, p<0.01, respectively). BO treatment exhibited reduced both visceral fat mass and hepatic
triacylglycerol content; moreover, BO treatment displayed significantly decreased both the average area of the cut of adipocytes and ballooning of hepatocytes. BO treatment exerted increased the
protein contents of
glucose transporter 4 (GLUT4) in skeletal muscle, and caused lowered
blood glucose levels. BO treatment displayed increased levels of phosphorylated
AMP-activated protein kinase (AMPK) in both skeletal muscle and liver tissue. Furthermore, BO reduced the hepatic expression of
glucose-6-phosphatase (G6Pase) and phosphenolpyruvate carboxykinase (PEPCK) and
glucose production. Therefore, it is possible that the activation of AMPK by BO leads to diminished gluconeogenesis in liver tissue. BO increased hepatic expressions of
peroxisome proliferator-activated receptor α (PPARα), whereas down-regulating decreasing expressions of
fatty acid synthesis, including
sterol regulatory element binding protein 1c (SREBP1c) and
fatty acid synthase (FAS), resulting in a decrease in circulating
triglycerides. This study originally provides the evidence that amelioration of dyslipidemic and diabetic state by BO in HF-fed mice occurred by regulation of GLUT4, SREBP1c, FAS, PPARα,
adiponectin and AMPK phosphorylation.