AMP-activated protein kinase α2 subunit is required for the preservation of hepatic insulin sensitivity by n-3 polyunsaturated fatty acids

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  • Tomas Jelenik
  • Martin Rossmeisl
  • Ondrej Kuda
  • Zuzana Macek Jilkova
  • Dasa Medrikova
  • Vladimir Kus
  • Michal Hensler
  • Petra Janovska
  • Ivan Miksik
  • Marcin Baranowski
  • Jan Gorski
  • Sophie Hébrard
  • Jensen, Thomas Elbenhardt
  • Pavel Flachs
  • Simon Hawley
  • Benoit Viollet
  • Jan Kopecky

Objective: The induction of obesity, dyslipidemia, and insulin resistance by high-fat diet in rodents can be prevented by n-3 long-chain polyunsaturated fatty acids (LC-PUFAs). We tested a hypothesis whether AMP-activated protein kinase (AMPK) has a role in the beneficial effects of n-3 LC-PUFAs.

Research design and methods: Mice with a wholebody deletion of the α2 catalytic subunit of AMPK (AMPKα2-/-) and their wild-type littermates were fed on either a low-fat chow, or a corn oil-based high-fat diet (cHF), or a cHF diet with 15% lipids replaced by n-3 LC-PUFA concentrate (cHF+F).

Results: Feeding a cHF diet induced obesity, dyslipidemia, hepatic steatosis, and whole-body insulin resistance in mice of both genotypes. Although cHF+F feeding increased hepatic AMPKα2 activity, the body weight gain, dyslipidemia, and the accumulation of hepatic triglycerides were prevented by the cHF+F diet to a similar degree in both AMPKα2-/- and wildtype mice in ad libitum-fed state. However, preservation of hepatic insulin sensitivity by n-3 LC-PUFAs required functional AMPKα2 and correlated with the induction of adiponectin and reduction in liver diacylglycerol content. Under hyperinsulinemic-euglycemic conditions, AMPKα2 was essential for preserving low levels of both hepatic and plasma triglycerides, as well as plasma free fatty acids, in response to the n-3 LC-PUFA treatment.

Conclusions: Our results show that n-3 LC-PUFAs prevent hepatic insulin resistance in an AMPKα2-dependent manner and support the role of adiponectin and hepatic diacylglycerols in the regulation of insulin sensitivity. AMPKα2 is also essential for hypolipidemic and antisteatotic effects of n-3 LC-PUFA under insulin-stimulated conditions.

Udgave nummer11
Sider (fra-til)2737-2746
Antal sider10
StatusUdgivet - 2010

ID: 210198045