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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AMP-activated protein kinase α2 subunit is required for the preservation of hepatic insulin sensitivity by n-3 polyunsaturated fatty acids. / Jelenik, Tomas; Rossmeisl, Martin; Kuda, Ondrej; Jilkova, Zuzana Macek; Medrikova, Dasa; Kus, Vladimir; Hensler, Michal; Janovska, Petra; Miksik, Ivan; Baranowski, Marcin; Gorski, Jan; Hébrard, Sophie; Jensen, Thomas Elbenhardt; Flachs, Pavel; Hawley, Simon; Viollet, Benoit; Kopecky, Jan.
In: Diabetes, Vol. 59, No. 11, 2010, p. 2737-2746.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - AMP-activated protein kinase α2 subunit is required for the preservation of hepatic insulin sensitivity by n-3 polyunsaturated fatty acids
AU - Jelenik, Tomas
AU - Rossmeisl, Martin
AU - Kuda, Ondrej
AU - Jilkova, Zuzana Macek
AU - Medrikova, Dasa
AU - Kus, Vladimir
AU - Hensler, Michal
AU - Janovska, Petra
AU - Miksik, Ivan
AU - Baranowski, Marcin
AU - Gorski, Jan
AU - Hébrard, Sophie
AU - Jensen, Thomas Elbenhardt
AU - Flachs, Pavel
AU - Hawley, Simon
AU - Viollet, Benoit
AU - Kopecky, Jan
PY - 2010
Y1 - 2010
N2 - 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.
AB - 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.
KW - Faculty of Science
U2 - 10.2337/db09-1716
DO - 10.2337/db09-1716
M3 - Journal article
C2 - 20693347
AN - SCOPUS:78049278390
VL - 59
SP - 2737
EP - 2746
JO - Diabetes
JF - Diabetes
SN - 0012-1797
IS - 11
ER -
ID: 210198045