Baicalein, a natural product, selectively activating AMPKα(2) and ameliorates metabolic disorder in diet-induced mice.
The aim of the present study was to determine the effect of baicalein on metabolic syndrome induced by a high-fat diet in mice. The mice developed obesity, dyslipidemia, fatty liver, diabetes and insulin resistance. These disorders were effectively normalized in baicalein-treated mice. Further investigation revealed that the inhibitory effect on inflammation and insulin resistance was mediated by inhibition of the MAPKs pathway and activation of the IRS1/PI3K/Akt pathway. The lipid-lowering effect was attributed to the blocking of synthesis way mediated by SERBP-1c, PPARγ and the increased fatty acid oxidation. All of these effects depended on AMPKα activation. These results were confirmed in the primary hepatocytes from wild type and AMPKα(2)(-/-) mice. However, the IRS-1/PI3K/AKT pathway showed no change, which may be due to the time of stimulation and concentration. Thus, these data suggested that baicalein protects mice from metabolic syndrome through an AMPKα(2)-dependent mechanism involving multiple intracellular signaling pathways.
Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan 430060, PR China.
Peng
P
Pu
Xin-An
XA
Wang
Mohamed
M
Salim
Li-Hua
LH
Zhu
Lang
L
Wang
Kvo-Jv
KJ
Chen
Jin-Feng
JF
Xiao
Wei
W
Deng
Hong-Wei
HW
Shi
Hong
H
Jiang
Hong-Liang
HL
Li
D055372:AMP-Activated Protein Kinases / Q000378:metabolism*; D000818:Animals; D053898:Biosynthetic Pathways / Q000235:genetics; D001786:Blood Glucose; D001835:Body Weight / Q000187:drug effects; D002478:Cells, Cultured; D018932:Chemokine CCL2 / Q000097:blood; D059305:Diet, High-Fat / Q000009:adverse effects*; D004365:Drugs, Chinese Herbal / Q000494:pharmacology* / Q000627:therapeutic use; D004734:Energy Metabolism; D020536:Enzyme Activators / Q000494:pharmacology* / Q000627:therapeutic use; D005227:Fatty Acids / Q000096:biosynthesis; D005234:Fatty Liver / Q000188:drug therapy / Q000209:etiology / Q000473:pathology; D044950:Flavanones / Q000494:pharmacology* / Q000627:therapeutic use; D015870:Gene Expression / Q000187:drug effects; D022781:Hepatocytes / Q000187:drug effects / Q000378:metabolism; D007333:Insulin Resistance; D020935:MAP Kinase Signaling System; D008297:Male; D024821:Metabolic Syndrome / Q000188:drug therapy* / Q000201:enzymology / Q000209:etiology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D056128:Obesity, Abdominal / Q000188:drug therapy / Q000201:enzymology / Q000209:etiology; D018384:Oxidative Stress; D014409:Tumor Necrosis Factor-alpha / Q000097:blood
D001786:Blood Glucose; C491768:Ccl2 protein, mouse; D018932:Chemokine CCL2; D004365:Drugs, Chinese Herbal; D020536:Enzyme Activators; D005227:Fatty Acids; D044950:Flavanones; D014409:Tumor Necrosis Factor-alpha; C006680:baicalein; C534978:Prkaa2 protein, mouse; D020928:Mitogen-Activated Protein Kinases; D055372:AMP-Activated Protein Kinases