Tormentic acid, a major component of suspension cells of Eriobotrya japonica, suppresses high-fat diet-induced diabetes and hyperlipidemia by glucose transporter 4 and AMP-activated protein kinase phosphorylation.

Abstract

This study was designed to evaluate the effects and mechanism of tormentic acid (PTA) on diabetes and dyslipidemia in high-fat (HF)-fed mice. Feeding C57BL/6J mice with a HF diet for 12 weeks induced type 2 diabetes and hyperlipidemia. During the last 4 weeks, the mice were given orally PTA (at two dosages) or rosiglitazone (Rosi) or water. In this study, the HF diet increased glucose, triglyceride, insulin, and leptin levels, whereas PTA effectively prevented these phenomena and ameliorated insulin resistance. PTA reduced visceral fat mass and hepatic triacylglycerol contents; moreover, PTA significantly decreased both the area of adipocytes and ballooning degeneration of hepatocytes. PTA caused increased skeletal muscular AMP-activated protein kinase (AMPK) phosphorylation and Akt phosphorylation and glucose transporter 4 (GLUT4) proteins, but reduced the hepatic expressions of phosphenolpyruvate carboxykinase (PEPCK) and glucose-6-phosphatase (G6 Pase) genes. PTA enhanced skeletal muscular Akt phosphorylation and increased insulin sensitivity. PTA also enhanced phospho-AMPK in the liver. Therefore, it is possible that the activation of AMPK by PTA results in decreasing hepatic glucose production while increasing skeletal muscular GLUT4 contents, thus contributing to attenuating the diabetic state. Moreover, PTA exhibits an antihyperlipidemic effect by down-regulations of the hepatic sterol regulatory element binding protein-1c (SREBP-1c) and apolipoprotein C-III (apo C-III) and an increased peroxisome proliferator activated receptor (PPAR)-α expression, thus resulting in decreases in blood triglycerides. These findings demonstrated that PTA was effective for the treatment of diabetes and hyperlipidemia in HF-fed mice.

• Authors: Jin-Bin Wu, Yueh-Hsiung Kuo, Cheng-Hsiu Lin, Hui-Ya Ho, Chun-Ching Shih
• Journal: Journal of agricultural and food chemistry (J Agric Food Chem) Vol. 62 Issue 44 Pg. 10717-26 (Nov 05 2014) ISSN: 1520-5118 [Electronic] United States
• PMID: 25317836 (Publication Type: Journal Article)

Chemical References

• Blood Glucose
• Glucose Transporter Type 4
• Insulin
• Plant Extracts
• Sterol Regulatory Element Binding Protein 1
• Triglycerides
• Triterpenes
• euscaphic acid
• AMP-Activated Protein Kinases

Topics

• AMP-Activated Protein Kinases (genetics, metabolism)
• Animals
• Blood Glucose (metabolism)
• Cells, Cultured
• Diabetes Mellitus, Type 2 (drug therapy, enzymology, genetics, metabolism)
• Diet, High-Fat (adverse effects)
• Eriobotrya (chemistry, growth & development)
• Glucose Transporter Type 4 (genetics, metabolism)
• Humans
• Hyperlipidemias (drug therapy, enzymology, genetics, metabolism)
• Insulin (metabolism)
• Liver (enzymology, metabolism)
• Male
• Mice
• Mice, Inbred C57BL
• Muscle, Skeletal (enzymology, metabolism)
• Phosphorylation (drug effects)
• Plant Extracts (administration & dosage)
• Sterol Regulatory Element Binding Protein 1 (genetics, metabolism)
• Triglycerides (metabolism)
• Triterpenes (administration & dosage)