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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
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. RE...
Autores principales: | , , , , , , , , , , , , , , , , |
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Formato: | Texto |
Lenguaje: | English |
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American Diabetes Association
2010
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2963531/ https://www.ncbi.nlm.nih.gov/pubmed/20693347 http://dx.doi.org/10.2337/db09-1716 |
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author | 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 E. Flachs, Pavel Hawley, Simon Viollet, Benoit Kopecky, Jan |
author_facet | 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 E. Flachs, Pavel Hawley, Simon Viollet, Benoit Kopecky, Jan |
author_sort | Jelenik, Tomas |
collection | PubMed |
description | 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 whole-body 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 wild-type 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. |
format | Text |
id | pubmed-2963531 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2010 |
publisher | American Diabetes Association |
record_format | MEDLINE/PubMed |
spelling | pubmed-29635312011-11-01 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 E. Flachs, Pavel Hawley, Simon Viollet, Benoit Kopecky, Jan Diabetes Metabolism 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 whole-body 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 wild-type 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. American Diabetes Association 2010-11 2010-08-06 /pmc/articles/PMC2963531/ /pubmed/20693347 http://dx.doi.org/10.2337/db09-1716 Text en © 2010 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered. See http://creativecommons.org/licenses/by-nc-nd/3.0/ for details. |
spellingShingle | Metabolism 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 E. Flachs, Pavel Hawley, Simon Viollet, Benoit Kopecky, Jan AMP-activated Protein Kinase α2 Subunit Is Required for the Preservation of Hepatic Insulin Sensitivity by n-3 Polyunsaturated Fatty Acids |
title | AMP-activated Protein Kinase α2 Subunit Is Required for the Preservation of Hepatic Insulin Sensitivity by n-3 Polyunsaturated Fatty Acids |
title_full | AMP-activated Protein Kinase α2 Subunit Is Required for the Preservation of Hepatic Insulin Sensitivity by n-3 Polyunsaturated Fatty Acids |
title_fullStr | AMP-activated Protein Kinase α2 Subunit Is Required for the Preservation of Hepatic Insulin Sensitivity by n-3 Polyunsaturated Fatty Acids |
title_full_unstemmed | AMP-activated Protein Kinase α2 Subunit Is Required for the Preservation of Hepatic Insulin Sensitivity by n-3 Polyunsaturated Fatty Acids |
title_short | AMP-activated Protein Kinase α2 Subunit Is Required for the Preservation of Hepatic Insulin Sensitivity by n-3 Polyunsaturated Fatty Acids |
title_sort | amp-activated protein kinase α2 subunit is required for the preservation of hepatic insulin sensitivity by n-3 polyunsaturated fatty acids |
topic | Metabolism |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2963531/ https://www.ncbi.nlm.nih.gov/pubmed/20693347 http://dx.doi.org/10.2337/db09-1716 |
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