AMP-activated Protein Kinase α2 Subunit Is Required for the Preservation of Hepatic Insulin Sensitivity by n-3 Polyunsaturated Fatty Acids
| Autor: | Thomas E. Jensen, Jan Kopecky, Martin Rossmeisl, Ivan Mikšík, Simon A. Hawley, Marcin Baranowski, Pavel Flachs, Vladimir Kus, Petra Janovska, Zuzana Macek Jilkova, Benoit Viollet, Ondrej Kuda, Dasa Medrikova, Sophie Hébrard, Jan Górski, Tomas Jelenik, M Hensler |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2010 |
| Předmět: |
medicine.medical_specialty
Endocrinology Diabetes and Metabolism medicine.medical_treatment Cell Culture Techniques AMP-Activated Protein Kinases Mice Insulin resistance AMP-activated protein kinase Internal medicine Hyperinsulinism Fatty Acids Omega-3 Internal Medicine medicine Animals Diet Fat-Restricted chemistry.chemical_classification Metabolic Syndrome Mice Knockout Adiponectin biology Insulin Fatty liver Glucose clamp technique medicine.disease Dietary Fats Protein Subunits Endocrinology Metabolism chemistry Liver biology.protein Fatty Acids Unsaturated Glucose Clamp Technique Hepatocytes Insulin Resistance Dyslipidemia Polyunsaturated fatty acid |
| Zdroj: | Diabetes |
| ISSN: | 1939-327X 0012-1797 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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