AMP-activated protein kinase α2 subunit is required for the preservation of hepatic insulin sensitivity by n-3 polyunsaturated fatty acids
Jazyk angličtina Země Spojené státy americké Médium print-electronic
Typ dokumentu časopisecké články, práce podpořená grantem
PubMed
20693347
PubMed Central
PMC2963531
DOI
10.2337/db09-1716
PII: db09-1716
Knihovny.cz E-zdroje
- MeSH
- buněčné kultury MeSH
- dieta s omezením tuků MeSH
- dietní tuky farmakologie MeSH
- glykemický clamp MeSH
- hepatocyty cytologie fyziologie MeSH
- hyperinzulinismus MeSH
- inzulinová rezistence MeSH
- játra účinky léků enzymologie fyziologie MeSH
- kyseliny mastné omega-3 metabolismus terapeutické užití MeSH
- metabolický syndrom prevence a kontrola MeSH
- myši knockoutované MeSH
- myši MeSH
- nenasycené mastné kyseliny metabolismus farmakologie MeSH
- podjednotky proteinů metabolismus MeSH
- proteinkinasy aktivované AMP nedostatek metabolismus MeSH
- zvířata MeSH
- Check Tag
- myši MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- dietní tuky MeSH
- kyseliny mastné omega-3 MeSH
- nenasycené mastné kyseliny MeSH
- podjednotky proteinů MeSH
- Prkaa2 protein, mouse MeSH Prohlížeč
- proteinkinasy aktivované AMP MeSH
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.
Zobrazit více v PubMed
Flachs P, Rossmeisl M, Bryhn M, Kopecky J. Cellular and molecular effects of n-3 polyunsaturated fatty acids on adipose tissue biology and metabolism. Clin Sci 2009;116:1–16 PubMed
Nettleton JA, Katz R. n-3 long-chain polyunsaturated fatty acids in type 2 diabetes: a review. J Am Diet Assoc 2005;105:428–440 PubMed
Mori TA, Bao DQ, Burke V, Puddey IB, Watts GF, Beilin LJ. Dietary fish as a major component of a weight-loss diet: effect on serum lipids, glucose, and insulin metabolism in overweight hypertensive subjects. Am J Clin Nutr 1999;70:817–825 PubMed
Couet C, Delarue J, Ritz P, Antoine JM, Lamisse F. Effect of dietary fish oil on body fat mass and basal fat oxidation in healthy adults. Int J Obes 1997;21:637–643 PubMed
Ruzickova J, Rossmeisl M, Prazak T, Flachs P, Sponarova J, Veck M, Tvrzicka E, Bryhn M, Kopecky J. Omega-3 PUFA of marine origin limit diet-induced obesity in mice by reducing cellularity of adipose tissue. Lipids 2004;39:1177–1185 PubMed
Flachs P, Horakova O, Brauner P, Rossmeisl M, Pecina P, Franssen-van Hal N, Ruzickova J, Sponarova J, Drahota Z, Vlcek C, Keijer J, Houstek J, Kopecky J. Polyunsaturated fatty acids of marine origin upregulate mitochondrial biogenesis and induce beta-oxidation in white fat. Diabetologia 2005;48:2365–2375 PubMed
Ikemoto S, Takahashi M, Tsunoda N, Maruyama K, Itakura H, Ezaki O. High-fat diet-induced hyperglycemia and obesity in mice: differential effects of dietary oils. Metabolism 1996;45:1539–1546 PubMed
Kuda O, Jelenik T, Jilkova Z, Flachs P, Rossmeisl M, Hensler M, Kazdova L, Ogston N, Baranowski M, Gorski J, Janovska P, Kus V, Polak J, Mohamed-Ali V, Burcelin R, Cinti S, Bryhn M, Kopecky J. n-3 fatty acids and rosiglitazone improve insulin sensitivity through additive stimulatory effects on muscle glycogen synthesis in mice fed a high-fat diet. Diabetologia 2009;52:941–951 PubMed
Storlien LH, Kraegen EW, Chisholm DJ, Ford GL, Bruce DG, Pascoe WS. Fish oil prevents insulin resistance induced by high-fat feeding in rats. Science 1987;237:885–888 PubMed
Jucker BM, Cline GW, Barucci N, Shulman GI. Differential effects of safflower oil versus fish oil feeding on insulin-stimulated glycogen synthesis, glycolysis, and pyruvate dehydrogenase flux in skeletal muscle: a 13C nuclear magnetic resonance study. Diabetes 1999;48:134–140 PubMed
Fasching P, Ratheiser K, Waldhäusl W, Rohac M, Osterrode W, Nowotny P, Vierhapper H. Metabolic effects of fish-oil supplementation in patients with impaired glucose tolerance. Diabetes 1991;40:583–589 PubMed
Pelikánová T, Kohout M, Válek J, Kazdová L, Base J. Metabolic effects of omega-3 fatty acids in type 2 (non-insulin-dependent) diabetic patients. Ann N Y Acad Sci 1993;683:272–278 PubMed
Teran-Garcia M, Adamson AW, Yu G, Rufo C, Suchankova G, Dreesen TD, Tekle M, Clarke SD, Gettys TW. Polyunsaturated fatty acid suppression of fatty acid synthase (FASN): evidence for dietary modulation of NF-Y binding to the Fasn promoter by SREBP-1c. Biochem J 2007;402:591–600 PubMed PMC
Sanderson LM, de Groot PJ, Hooiveld GJ, Koppen A, Kalkhoven E, Müller M, Kersten S. Effect of synthetic dietary triglycerides: a novel research paradigm for nutrigenomics. PLoS One 2008;3:e1681. PubMed PMC
van Schothorst EM, Flachs P, Franssen-van Hal NL, Kuda O, Bunschoten A, Molthoff J, Vink C, Hooiveld GJ, Kopecky J, Keijer J. Induction of lipid oxidation by polyunsaturated fatty acids of marine origin in small intestine of mice fed a high-fat diet. BMC Genomics 2009;10:110. PubMed PMC
Neschen S, Morino K, Dong J, Wang-Fischer Y, Cline GW, Romanelli AJ, Rossbacher JC, Moore IK, Regittnig W, Munoz DS, Kim JH, Shulman GI. n-3 Fatty acids preserve insulin sensitivity in vivo in a peroxisome proliferator-activated receptor-alpha-dependent manner. Diabetes 2007;56:1034–1041 PubMed
Serhan CN. Novel omega-3-derived local mediators in anti-inflammation and resolution. Pharmacol Ther 2005;105:7–21 PubMed
González-Périz A, Horrillo R, Ferré N, Gronert K, Dong B, Morán-Salvador E, Titos E, Martínez-Clemente M, López-Parra M, Arroyo V, Clària J. Obesity-induced insulin resistance and hepatic steatosis are alleviated by omega-3 fatty acids: a role for resolvins and protectins. FASEB J 2009;23:1946–1957 PubMed PMC
Jump DB. Fatty acid regulation of gene transcription. Crit Rev Clin Lab Sci 2004;41:41–78 PubMed
Neschen S, Morino K, Rossbacher JC, Pongratz RL, Cline GW, Sono S, Gillum M, Shulman GI. Fish oil regulates adiponectin secretion by a peroxisome proliferator-activated receptor-gamma-dependent mechanism in mice. Diabetes 2006;55:924–928 PubMed
Dentin R, Benhamed F, Pégorier JP, Foufelle F, Viollet B, Vaulont S, Girard J, Postic C. Polyunsaturated fatty acids suppress glycolytic and lipogenic genes through the inhibition of ChREBP nuclear protein translocation. J Clin Invest 2005;115:2843–2854 PubMed PMC
Suchankova G, Tekle M, Saha AK, Ruderman NB, Clarke SD, Gettys TW. Dietary polyunsaturated fatty acids enhance hepatic AMP-activated protein kinase activity in rats. Biochem Biophys Res Commun 2005;326:851–858 PubMed
Gabler NK, Radcliffe JS, Spencer JD, Webel DM, Spurlock ME. Feeding long-chain n-3 polyunsaturated fatty acids during gestation increases intestinal glucose absorption potentially via the acute activation of AMPK. J Nutr Biochem 2009;20:17–25 PubMed
Kopecky J, Rossmeisl M, Flachs P, Kuda O, Brauner P, Jilkova Z, Stankova B, Tvrzicka E, Bryhn M. n-3 PUFA: bioavailability and modulation of adipose tissue function. Proc Nutr Soc 2009;68:361–369 PubMed
Carling D. The AMP-activated protein kinase cascade–a unifying system for energy control. Trends Biochem Sci 2004;29:18–24 PubMed
Viollet B, Andreelli F, Jørgensen SB, Perrin C, Geloen A, Flamez D, Mu J, Lenzner C, Baud O, Bennoun M, Gomas E, Nicolas G, Wojtaszewski JF, Kahn A, Carling D, Schuit FC, Birnbaum MJ, Richter EA, Burcelin R, Vaulont S. The AMP-activated protein kinase alpha2 catalytic subunit controls whole-body insulin sensitivity. J Clin Invest 2003;111:91–98 PubMed PMC
Andreelli F, Foretz M, Knauf C, Cani PD, Perrin C, Iglesias MA, Pillot B, Bado A, Tronche F, Mithieux G, Vaulont S, Burcelin R, Viollet B. Liver adenosine monophosphate-activated kinase-alpha2 catalytic subunit is a key target for the control of hepatic glucose production by adiponectin and leptin but not insulin. Endocrinology 2006;147:2432–2441 PubMed
Foretz M, Ancellin N, Andreelli F, Saintillan Y, Grondin P, Kahn A, Thorens B, Vaulont S, Viollet B. Short-term overexpression of a constitutively active form of AMP-activated protein kinase in the liver leads to mild hypoglycemia and fatty liver. Diabetes 2005;54:1331–1339 PubMed
Zhang BB, Zhou G, Li C. AMPK: an emerging drug target for diabetes and the metabolic syndrome. Cell Metab 2009;9:407–416 PubMed
Kahn BB, Alquier T, Carling D, Hardie DG. AMP-activated protein kinase: ancient energy gauge provides clues to modern understanding of metabolism. Cell Metab 2005;1:15–25 PubMed
Polak J, Kovacova Z, Jacek M, Klimcakova E, Kovacikova M, Vitkova M, Kuda O, Sebela M, Samcova E, Stich V. An increase in plasma adiponectin multimeric complexes follows hypocaloric diet-induced weight loss in obese and overweight pre-menopausal women. Clin Sci (Lond) 2007;112:557–565 PubMed
Hardie DG, Salt IP, Davies SP. Analysis of the role of the AMP-activated protein kinase in the response to cellular stress. Methods Mol Biol 2000;99:63–74 PubMed
Burcelin R, Crivelli V, Dacosta A, Roy-Tirelli A, Thorens B. Heterogeneous metabolic adaptation of C57BL/6J mice to high-fat diet. Am J Physiol Endocrinol Metab 2002;282:E834–E842 PubMed
Foretz M, Guichard C, Ferré P, Foufelle F. Sterol regulatory element binding protein-1c is a major mediator of insulin action on the hepatic expression of glucokinase and lipogenesis-related genes. Proc Natl Acad Sci U S A 1999;96:12737–12742 PubMed PMC
Yamauchi T, Kamon J, Minokoshi Y, Ito Y, Waki H, Uchida S, Yamashita S, Noda M, Kita S, Ueki K, Eto K, Akanuma Y, Froguel P, Foufelle F, Ferre P, Carling D, Kimura S, Nagai R, Kahn BB, Kadowaki T. Adiponectin stimulates glucose utilization and fatty-acid oxidation by activating AMP-activated protein kinase. Nat Med 2002;8:1288–1295 PubMed
Kajikawa S, Harada T, Kawashima A, Imada K, Mizuguchi K. Highly purified eicosapentaenoic acid prevents the progression of hepatic steatosis by repressing monounsaturated fatty acid synthesis in high-fat/high-sucrose diet-fed mice. Prostaglandins Leukot Essent Fatty Acids 2009;80(4):229–238 PubMed
Uyeda K, Repa JJ. Carbohydrate response element binding protein, ChREBP, a transcription factor coupling hepatic glucose utilization and lipid synthesis. Cell Metab 2006;4:107–110 PubMed
Wakelam MJO. Diacylglycerol—when is it an intracellular messenger? BBA-Mol Cell Biol Lipids 1998;1436:117–126 PubMed
Schmitz-Peiffer C, Biden TJ. Protein kinase C function in muscle, liver, and beta-cells and its therapeutic implications for type 2 diabetes. Diabetes 2008;57:1774–1783 PubMed PMC
Donnelly KL, Smith CI, Schwarzenberg SJ, Jessurun J, Boldt MD, Parks EJ. Sources of fatty acids stored in liver and secreted via lipoproteins in patients with nonalcoholic fatty liver disease. J Clin Invest 2005;115:1343–1351 PubMed PMC
Ohira M, Miyashita Y, Murano T, Watanabe F, Shirai K. Metformin promotes induction of lipoprotein lipase in skeletal muscle through activation of adenosine monophosphate-activated protein kinase. Metabolism 2009;58:1408–1414 PubMed
Daval M, Diot-Dupuy F, Bazin R, Hainault I, Viollet B, Vaulont S, Hajduch E, Ferré P, Foufelle F. Anti-lipolytic action of AMP-activated protein kinase in rodent adipocytes. J Biol Chem 2005;280:25250–25257 PubMed
Dobrzyn A, Dobrzyn P, Miyazaki M, Ntambi JM. Polyunsaturated fatty acids do not activate AMP-activated protein kinase in mouse tissues. Biochem Biophys Res Commun 2005;332:892–896 PubMed
Salati LM, Clarke SD. Fatty acid inhibition of hormonal induction of acetyl-coenzyme A carboxylase in hepatocyte monolayers. Arch Biochem Biophys 1986;246:82–89 PubMed
Woods A, Johnstone SR, Dickerson K, Leiper FC, Fryer LG, Neumann D, Schlattner U, Wallimann T, Carlson M, Carling D. LKB1 is the upstream kinase in the AMP-activated protein kinase cascade. Curr Biol 2003;13:2004–2008 PubMed
Flachs P, Mohamed-Ali V, Horakova O, Rossmeisl M, Hosseinzadeh-Attar MJ, Hensler M, Ruzickova J, Kopecky J. Polyunsaturated fatty acids of marine origin induce adiponectin in mice fed a high-fat diet. Diabetologia 2006;49:394–397 PubMed
Itoh M, Suganami T, Satoh N, Tanimoto-Koyama K, Yuan X, Tanaka M, Kawano H, Yano T, Aoe S, Takeya M, Shimatsu A, Kuzuya H, Kamei Y, Ogawa Y. Increased adiponectin secretion by highly purified eicosapentaenoic acid in rodent models of obesity and human obese subjects. Arterioscler Thromb Vasc Biol 2007;27:1918–1925 PubMed
Nawrocki AR, Rajala MW, Tomas E, Pajvani UB, Saha AK, Trumbauer ME, Pang Z, Chen AS, Ruderman NB, Chen H, Rossetti L, Scherer PE. Mice lacking adiponectin show decreased hepatic insulin sensitivity and reduced responsiveness to peroxisome proliferator-activated receptor gamma agonists. J Biol Chem 2006;281:2654–2660 PubMed
Villena JA, Viollet B, Andreelli F, Kahn A, Vaulont S, Sul HS. Induced adiposity and adipocyte hypertrophy in mice lacking the AMP-activated protein kinase-alpha2 subunit. Diabetes 2004;53:2242–2249 PubMed
Cheung PC, Salt IP, Davies SP, Hardie DG, Carling D. Characterization of AMP-activated protein kinase gamma-subunit isoforms and their role in AMP binding. Biochem J 2000;346:659–669 PubMed PMC
Metformin acutely lowers blood glucose levels by inhibition of intestinal glucose transport
The inhibition of fat cell proliferation by n-3 fatty acids in dietary obese mice