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

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

doi:10.2337/db09-1716

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

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^*

^*Corresponding author af dette arbejde

67 Citationer (Scopus)

Abstract

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.

Originalsprog	Engelsk
Tidsskrift	Diabetes
Vol/bind	59
Udgave nummer	11
Sider (fra-til)	2737-2746
Antal sider	10
ISSN	0012-1797
DOI	https://doi.org/10.2337/db09-1716
Status	Udgivet - 2010

Emneord

Det Natur- og Biovidenskabelige Fakultet

FN’s Verdensmål

Dette resultat bidrager til følgende verdensmål

Adgang til dokumentet

10.2337/db09-1716

2737.full.pdfForlagets udgivne version, 229 KBLicens: CC BY-NC-ND

Citationsformater

Jelenik, T., Rossmeisl, M., Kuda, O., Jilkova, Z. M., Medrikova, D., Kus, V., Hensler, M., Janovska, P., Miksik, I., Baranowski, M., Gorski, J., Hébrard, S., Jensen, T. E., Flachs, P., Hawley, S., Viollet, B., & Kopecky, J. (2010). AMP-activated protein kinase α2 subunit is required for the preservation of hepatic insulin sensitivity by n-3 polyunsaturated fatty acids. Diabetes, 59(11), 2737-2746. https://doi.org/10.2337/db09-1716

Jelenik, T, Rossmeisl, M, Kuda, O, Jilkova, ZM, Medrikova, D, Kus, V, Hensler, M, Janovska, P, Miksik, I, Baranowski, M, Gorski, J, Hébrard, S, Jensen, TE, Flachs, P, Hawley, S, Viollet, B & Kopecky, J 2010, 'AMP-activated protein kinase α2 subunit is required for the preservation of hepatic insulin sensitivity by n-3 polyunsaturated fatty acids', Diabetes, bind 59, nr. 11, s. 2737-2746. https://doi.org/10.2337/db09-1716

@article{d9ac1b79fa4343c2b4cece95719457c5,

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

abstract = "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.",

keywords = "Faculty of Science",

author = "Tomas Jelenik and Martin Rossmeisl and Ondrej Kuda and Jilkova, {Zuzana Macek} and Dasa Medrikova and Vladimir Kus and Michal Hensler and Petra Janovska and Ivan Miksik and Marcin Baranowski and Jan Gorski and Sophie H{\'e}brard and Jensen, {Thomas Elbenhardt} and Pavel Flachs and Simon Hawley and Benoit Viollet and Jan Kopecky",

year = "2010",

doi = "10.2337/db09-1716",

language = "English",

volume = "59",

pages = "2737--2746",

journal = "Diabetes",

issn = "0012-1797",

publisher = "American Diabetes Association",

number = "11",

}

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

SN - 0012-1797

VL - 59

SP - 2737

EP - 2746

JO - Diabetes

JF - Diabetes

IS - 11

ER -

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

Abstract

Emneord

FN’s Verdensmål

Adgang til dokumentet

Fingeraftryk

Citationsformater