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GGEx reduces fatty acid oxidation in skeletal muscle of Otsuka Long-Evans Tokushima fatty(OLETF) rats

ABSTRACT, INTRODUCTION, PURPOSE
GGEx regulates fatty acid oxidation in skeletal muscle of
Otsuka Long-Evans Tokushima fatty (OLETF) rats.
JEONG Sunhyo, LEE Jinmi, CHOI Seolhwa, JUNG Yang Sam1, SHIN Soon Shik1 and YOON Michung*
ABSTRACT

To investigate the mechanism by which Gyeongshingangjeehwan (GGEx), an herbal medicine widely used in oriental medicine, regulates obesity, we measured the expression of genes involved in fatty acid metabolism in Otsuka Long-Evans Tokushima fatty (OLETF) rats, an animal model of obesity. Rats treated with GGEx stimulate fatty acid oxidation through activation of PPAR? and PPAR? in skeletal muscle compared with vehicle-treated controls. GGEx increased not only mRNA levels of PPAR? target enzymes responsible for mitochondrial fatty acid ?-oxidation (acyl-CoA dehydrogenases), but also mRNA levels of PPAR? target enzyme responsible for lipoprotein catabolism (lipoprotein lipase). Moreover, mRNA levels of uncoupling protein 1 (UCP1) in brown adipose tissue were also increased by GGEx. In conclusion, these results suggest that GGEx regulates fatty acid oxidation through transcriptional activation of skeletal muscle PPAR? and PPAR? target enzymes and brown adipose UCP1, contributing to the prevention of obesity in OLETF rats.
INTRODUCTION

Peroxisome proliferator-activated receptors (PPARs) are lipid-activated transcription factors playing important regulatory functions in development and metabolism. PPARα and PPARγ are the most extensively examined and characterized, mainly because they are activated by marked hypolipidemic and insulin sensitizer compounds, such as fibrates and thiazolidinediones. It has been established that the third member of the family, PPARβ is implicated in developmental regulations, but until recently, its role in metabolism remained unclear. The availability of specific PPARβ agonists and of appropriate cellular and animal models revealed that PPARβ plays a crucial role in fatty acid metabolism in several tissues. Treatment of obese animals with PPARβ agonists results in normalization of metabolic parameters and reduction of adiposity. Activation ofther nuclear receptor promotes fatty acid burning in skeletal muscle and adipose tissue by upregulation of fatty acid uptake, β-oxidation and energy uncoupling. PPARβ is also involved in the adaptive metabolic responses of skeletal muscle to environmental changes, such as long-term fasting or physical exercise, by controlling the number of oxidative myofibers. These observations strongly suggest that PPARβ agonists may have therapeutic usefulness in metabolic syndrome by increasing fatty acid consumption and decreasing obesity.


Metabolic integration by PPARs. The three PPAR isoforms regulate lipid and glucose homeostasis through their coordinated activities in liver, muscle and adipose tissue.
PURPOSE

The aim of this study was to investigate the mechanism by which Gyeongshingangjeehwan(GGE),an herbal medicine widely used in oriental medicine, regulates obesity.