ABSTRACT
AIM OF THE STUDY: Gyeongshingangjeehwan (GGEx), which is a polyherbal drug composed of four medicinal plants, has traditionally been used as anti-obesity drug in Korean local clinics. Thus, we investigated the effects of GGEx on visceral adiposity and examined whether adipose peroxisome proliferator-activated receptor alpha (PPARalpha) activation is involved in this process. MATERIALS AND METHODS: After Obese Otsuka Long-Evans Tokushima Fatty (OLETF) rats and differentiated 3T3-L1 adipocytes were treated with GGEx, we studied the effects of GGEx on not only visceral white adipose tissue (WAT) mass and adipocyte size, but also the expression of adipocyte marker and PPARalpha target genes. RESULTS: Administration of GGEx to obese rats for 8 weeks decreased visceral WAT weight by 30% and the size of adipocytes in mesenteric WAT by 31% without weight changes of other organs. Concomitantly, GGEx increased mRNA levels of PPARalpha target genes responsible for fatty acid beta-oxidation in mesenteric WAT whereas decreased mRNA expression of adipocyte markers, such as PPARgamma, aP2 and leptin. Serological studies demonstrated that plasma levels of free fatty acids and triglycerides as well as insulin and glucose were decreased following GGEx treatment. Consistent with the in vivo data, GGEx increased PPARalpha reporter gene activity and induced the mRNA expression of PPARalpha target genes involved in mitochondrial fatty acid beta-oxidation in 3T3-L1 cells. GGEx also inhibited triglyceride accumulation in these cells. CONCLUSION: These results suggest that GGEx promotes the reductions in visceral fat mass and adipocyte size in obese animals, and that this event may be mediated by adipose PPARalpha activation.
Subject(s)
Anti-Obesity Agents/pharmacology , Intra-Abdominal Fat/drug effects , Medicine, Korean Traditional , PPAR alpha/metabolism , Plant Extracts/pharmacology , 3T3-L1 Cells , Adipocytes/drug effects , Adipocytes/metabolism , Adipocytes/pathology , Animals , Biomarkers/blood , Biomarkers/metabolism , Cell Differentiation/drug effects , Cell Size/drug effects , Gene Expression Regulation/drug effects , Intra-Abdominal Fat/metabolism , Intra-Abdominal Fat/pathology , Lipids/analysis , Lipids/blood , Male , Mice , Obesity/drug therapy , Obesity/physiopathology , Organ Size/drug effects , PPAR alpha/genetics , Phytotherapy , Plants, Medicinal , Rats , Rats, Inbred OLETFABSTRACT
Gyeongshingangjeehwan (GGEx), which comprises Liriope platyphylla F.T. Wang & T. Tang (Liliaceae), Platycodongrandiflorum A. DC. (Campanulaceae), Schisandrachinensis K. Koch (Magnoliaceae), and Ephedra sinica Stapf (Ephedraceae), has traditionally been used as an anti-obesity drug in Korean local clinics, although there is no evidence concerning the scientific analyses of its effects and mechanism(s) of action. Thus, we investigated the effects of GGEx on obesity, as well as the mechanism by which GGEx functions, in Otsuka Long-Evans Tokushima Fatty (OLETF) male rats. Compared with obese OLETF control rats, administration of GGEx for 8 weeks significantly decreased food intake and plasma leptin levels as well as body weight gain and abdominal fat in OLETF rats. GGEx treatment not only decreased circulating triglycerides, but also inhibited lipid accumulation in the liver. GGEx increased the hepatic mRNA levels of PPARalpha target genes responsible for fatty acid beta-oxidation. Consistent with the in vivo data, GGEx elevated PPARalpha reporter gene expression in NMu2Li liver cells. These results suggest that GGEx may effectively prevent obesity and hypertriglyceridemia in part through the inhibition of feeding and the activation of hepatic PPARalpha.
