Flavonoid derivative exerts an antidiabetic effect via AMPK activation in diet-induced obesity mice.
In our previous study, a derivative of tiliroside, 3-O-[(E)-4-(4-ethoxyphenyl)-2-oxobut-3-en-1-yl]kaempferol (Fla-OEt) significantly enhanced glucose consumption in insulin resistant HepG2 cells. This article deals with the antihyperglycemic and antihyperlipidemic effects of Fla-OEt in diet-induced obesity (DIO) mice. Daily administration of Fla-OEt significantly decreased oral glucose tolerance test, intraperitoneal insulin tolerance test and serum lipids. Hyperinsulinemic-euglycemic clamp and the ratio of high-density-lipoprotein/low-density-lipoprotein with Fla-OEt treatment were increased comparing with high-fat diet (HFD) group, so lipid metabolism was improved. Histopathology examination showed that the Fla-OEt restored the damage of adipose tissues and liver in DIO mice. Moreover, compared with HFD group, Fla-OEt treatment significantly increased the phosphorylation of AMPK and ACC in adiposity tissues, liver, and muscles. The mechanism of its action might be the activation of AMPK pathway. It appears that Fla-OEt is worth further study for development as a lead compound for a potential antidiabetic agent.
a Research Center of Basic Medical Sciences , Tianjin Medical University , Tianjin , People's Republic of China.
Ying
Y
Chen
b Tianjin Key Laboratory on Technologies Enabling Development Clinical Therapeutics and Diagnostics (Theranostics), School of Pharmacy , Tianjin Medical University , Tianjin , People's Republic of China.
Chang
C
Zhang
b Tianjin Key Laboratory on Technologies Enabling Development Clinical Therapeutics and Diagnostics (Theranostics), School of Pharmacy , Tianjin Medical University , Tianjin , People's Republic of China.
Mei-Na
MN
Jin
a Research Center of Basic Medical Sciences , Tianjin Medical University , Tianjin , People's Republic of China.|b Tianjin Key Laboratory on Technologies Enabling Development Clinical Therapeutics and Diagnostics (Theranostics), School of Pharmacy , Tianjin Medical University , Tianjin , People's Republic of China.
Nan
N
Qin
b Tianjin Key Laboratory on Technologies Enabling Development Clinical Therapeutics and Diagnostics (Theranostics), School of Pharmacy , Tianjin Medical University , Tianjin , People's Republic of China.
Wei
W
Qiao
b Tianjin Key Laboratory on Technologies Enabling Development Clinical Therapeutics and Diagnostics (Theranostics), School of Pharmacy , Tianjin Medical University , Tianjin , People's Republic of China.
Xiao-Long
XL
Yue
a Research Center of Basic Medical Sciences , Tianjin Medical University , Tianjin , People's Republic of China.|b Tianjin Key Laboratory on Technologies Enabling Development Clinical Therapeutics and Diagnostics (Theranostics), School of Pharmacy , Tianjin Medical University , Tianjin , People's Republic of China.
Hong-Quan
HQ
Duan
c Key Laboratory of Immune Microenvironment and Disease of the Educational Ministry of China, Department of Immunology , Tianjin Medical University , Tianjin , People's Republic of China.
Wen-Yan
WY
Niu
D055372:AMP-Activated Protein Kinases / Q000378:metabolism*; D000273:Adipose Tissue / Q000187:drug effects; D000818:Animals; D059305:Diet, High-Fat; D005419:Flavonoids / Q000008:administration & dosage / Q000494:pharmacology*; D007004:Hypoglycemic Agents / Q000008:administration & dosage / Q000494:pharmacology*; D007333:Insulin Resistance; D050356:Lipid Metabolism / Q000187:drug effects; D008099:Liver / Q000187:drug effects; D008297:Male; D051379:Mice; D008820:Mice, Obese; D009765:Obesity / Q000188:drug therapy / Q000378:metabolism*; D010766:Phosphorylation / Q000187:drug effects
D005419:Flavonoids; D007004:Hypoglycemic Agents; C052083:tiliroside; D055372:AMP-Activated Protein Kinases
Fla-OEt; anti-obesity; insulin resistant; lipid metabolism