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

Research output: Contribution to journalJournal articleResearchpeer-review

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, Thomas Elbenhardt Jensen, 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.

Original languageEnglish
JournalDiabetes
Volume59
Issue number11
Pages (from-to)2737-2746
Number of pages10
ISSN0012-1797
DOIs
Publication statusPublished - 2010

ID: 210198045