Berberine improves lipid dysregulation in obesity by controlling central and peripheral AMPK activity.
AMP-activated protein kinase (AMPK) plays an important role in regulating whole body energy homeostasis. Recently, it has been demonstrated that berberine (BBR) exerts antiobesity and antidiabetic 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, hepatic and plasma triglyceride, and cholesterol contents. In the liver and muscle of db/db mice, BBR promoted AMPK activity and fatty acid oxidation and changed expression of genes involved in lipid metabolism. Additionally, intracerebroventricular 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.
Kim
Woo Sik
WS
Institute of Molecular Biology and Genetics, Department of Biological Sciences, Seoul National University, San 56-1, Sillim-Dong, Kwanak-Gu, Seoul 151-742, Korea.
Lee
Yun Sok
YS
Cha
Seung Hun
SH
Jeong
Hyun Woo
HW
Choe
Sung Sik
SS
Lee
Mi-Ran
MR
Oh
Goo Taeg
GT
Park
Hye-Sun
HS
Lee
Ki-Up
KU
Lane
M Daniel
MD
Kim
Jae Bum
JB
D000263:Adenylate Kinase / Q000378:metabolism*; D000818:Animals; D001599:Berberine / Q000494:pharmacology* / Q000627:therapeutic use*; D002478:Cells, Cultured; D003921:Diabetes Mellitus, Experimental / Q000150:complications / Q000188:drug therapy / Q000235:genetics; D004353:Drug Evaluation, Preclinical; D050171:Dyslipidemias / Q000150:complications / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism; D004789:Enzyme Activation / Q000187:drug effects; D005227:Fatty Acids / Q000378:metabolism; D005234:Fatty Liver / Q000150:complications / Q000188:drug therapy; D005786:Gene Expression Regulation / Q000187:drug effects; D000960:Hypolipidemic Agents / Q000494:pharmacology / Q000627:therapeutic use; D050356:Lipid Metabolism / Q000187:drug effects / Q000235:genetics; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009765:Obesity / Q000150:complications / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism; D010084:Oxidation-Reduction / Q000187:drug effects; D054411:Receptors, Leptin / Q000235:genetics
D005227:Fatty Acids; D000960:Hypolipidemic Agents; D054411:Receptors, Leptin; D001599:Berberine; D000263:Adenylate Kinase