Acetic acid activates hepatic AMPK and reduces hyperglycemia in diabetic KK-A(y) mice

Biochem Biophys Res Commun. 2006 Jun 2;344(2):597-604. doi: 10.1016/j.bbrc.2006.03.176. Epub 2006 Apr 5.


Acetic acid (AcOH), which is a short-chain fatty acid, is reported to have some beneficial effects on metabolism. To test the hypothesis that feeding of AcOH exerts beneficial effects on glucose homeostasis in type 2 diabetes, we fed either a standard diet or one containing 0.3% AcOH to KK-A(y) mice for 8 weeks. Fasting plasma glucose and HbA1c levels were lower in mice fed AcOH for 8 weeks than in control mice. AcOH also reduced the expression of genes involved in gluconeogenesis and lipogenesis, which is in part regulated by 5'-AMP-activated protein kinase (AMPK) in the liver. Finally, sodium acetate, in the form of neutralized AcOH, directly activated AMPK and lowered the expression of genes such as for glucose-6-phosphatase and sterol regulatory element binding protein-1 in rat hepatocytes. These results indicate that the hypoglycemic effect of AcOH might be due to activation of AMPK in the liver.

MeSH terms

  • AMP-Activated Protein Kinases
  • Acetic Acid / administration & dosage*
  • Animals
  • Diabetes Mellitus, Type 2 / complications
  • Diabetes Mellitus, Type 2 / drug therapy
  • Diabetes Mellitus, Type 2 / enzymology*
  • Disease Models, Animal
  • Enzyme Activation / drug effects
  • Hyperglycemia / drug therapy*
  • Hyperglycemia / enzymology*
  • Hyperglycemia / etiology
  • Liver / drug effects*
  • Liver / enzymology*
  • Male
  • Mice
  • Multienzyme Complexes / drug effects
  • Multienzyme Complexes / metabolism*
  • Protein Serine-Threonine Kinases / drug effects
  • Protein Serine-Threonine Kinases / metabolism*
  • Treatment Outcome


  • Multienzyme Complexes
  • Protein Serine-Threonine Kinases
  • AMP-Activated Protein Kinases
  • Acetic Acid