Submitted on August 20, 2008
Revised on January 15, 2009
Accepted on January 15, 2009
Berberine improves lipid dysregulation in obesity by controlling central and peripheral AMPK activity
Woo Sik Kim1, Yun Sok Lee1, Seung Hun Cha2, Hyun Woo Jeong3, Sung Sik Choe3, Mi-Ran Lee4, Goo Taeg Oh4, Hye-Sun Park5, Ki-Up Lee5, Daniel Lane6, and Jae Bum Kim7*
1 Seoul National Univesity
2 Johns Hopkins University School of Medicine
3 Seoul National university
4 Ewha Womans University
5 University of Ulsan College of Medicine
6 Johns Hopkins University
7 Seoul National University
* To whom correspondence should be addressed. E-mail: jaebkim{at}snu.ac.kr.
AMP-activated protein kinase (AMPK) plays an important role in regulating whole body energy homeostasis. Recently, we and others have reported that berberine (BBR) exerts anti-obesity and anti-diabetic effects in obese and diabetic rodent models through the activation of AMPK in peripheral tissues. Here we show that BBR improves lipid dysregulation and fatty liver in obese mice through central and peripheral actions. In obese db/db and ob/ob mice, BBR treatment reduced liver weight, and hepatic and plasma triglyceride and cholesterol contents. In liver and muscle of db/db mice, BBR promoted AMPK activity, fatty acid oxidation and changed expression of genes involved in lipid metabolism. Additionally, icv administration of BBR decreased the level of malonyl-CoA and stimulated the expression of fatty acid oxidation genes in skeletal muscle. Together, these data suggest that BBR would improve fatty liver in obese subjects, which is probably mediated not only by peripheral AMPK activation but also by neural signaling from the central nervous system.
