The Korean traditional medicine gyeongshingangjeehwan inhibits adipocyte hypertrophy and visceral adipose tissue accumulation by activating PPARalpha actions in rat white adipose tissues.
OBJECTIVE
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.


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.


CONCLUSIONS
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.
Shin
Soon Shik
SS
Department of Formula Sciences, College of Oriental Medicine, Dongeui University, Busan 614-052, Republic of Korea.
Jung
Yang Sam
YS
Yoon
Ki Hyeon
KH
Choi
Seolwha
S
Hong
Yeonhee
Y
Park
Dongmin
D
Lee
Hyunghee
H
Seo
Bu Il
BI
Lee
Hee Young
HY
Yoon
Michung
M
D041721:3T3-L1 Cells; D017667:Adipocytes / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D000818:Animals; D019440:Anti-Obesity Agents / Q000494:pharmacology*; D015415:Biomarkers / Q000097:blood / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects; D048429:Cell Size / Q000187:drug effects; D005786:Gene Expression Regulation / Q000187:drug effects; D050152:Intra-Abdominal Fat / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D008055:Lipids / Q000032:analysis / Q000097:blood; D008297:Male; D055670:Medicine, Korean Traditional; D051379:Mice; D009765:Obesity / Q000188:drug therapy / Q000503:physiopathology; D009929:Organ Size / Q000187:drug effects; D047493:PPAR alpha / Q000235:genetics / Q000378:metabolism*; D008517:Phytotherapy; D010936:Plant Extracts / Q000494:pharmacology*; D010946:Plants, Medicinal; D051381:Rats; D020334:Rats, Inbred OLETF
D019440:Anti-Obesity Agents; D015415:Biomarkers; D008055:Lipids; D047493:PPAR alpha; D010936:Plant Extracts; C548755:gyeongshingangjeehwan