AMPK phosphorylation of ACC2 is required for skeletal muscle fatty acid oxidation and insulin sensitivity in mice
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- 作者：Hayley M. O’Neill (1) (2)
James S. Lally (1)
Sandra Galic (2)
Melissa Thomas (3)
Paymon D. Azizi (1)
Morgan D. Fullerton (1)
Brennan K. Smith (1) (5)
Thomas Pulinilkunnil (6)
Zhiping Chen (2)
M. Constantine Samaan (4)
Sebastian B. Jorgensen (2) (7)
Jason R. B. Dyck (6)
Graham P. Holloway (5)
Thomas J. Hawke (3)
Bryce J. van Denderen (2)
Bruce E. Kemp (2)
Gregory R. Steinberg (1) (2) - 关键词：ACC2 ; AMPK ; Fatty acid oxidation ; Insulin resistance ; Knock ; in mice ; Malonyl ; CoA ; Skeletal muscle
- 刊名：Diabetologia
- 出版年：2014
- 出版时间：August 2014
- 年：2014
- 卷：57
- 期：8
- 页码：1693-1702
- 全文大小：630 KB
- 参考文献：1. Steinberg GR, Kemp BE (2009) AMPK in health and disease. Physiol Rev 89:1025-078 CrossRef
2. Steinberg GR, Jorgensen SB (2007) The AMP-activated protein kinase: role in regulation of skeletal muscle metabolism and insulin sensitivity. Mini-Rev Med Chem 7:519-26 CrossRef
3. Abu-Elheiga L, Jayakumar A, Baldini A, Chirala SS, Wakil SJ (1995) Human acetyl-CoA carboxylase: characterization, molecular cloning, and evidence for two isoforms. Proc Natl Acad Sci U S A 92:4011-015 CrossRef
4. Iverson AJ, Bianchi A, Nordlund AC, Witters LA (1990) Immunological analysis of acetyl-CoA carboxylase mass, tissue distribution and subunit composition. Biochem J 269:365-71
5. Abu-Elheiga L, Brinkley WR, Zhong L, Chirala SS, Woldegiorgis G, Wakil SJ (2000) The subcellular localization of acetyl-CoA carboxylase 2. Proc Natl Acad Sci U S A 97:1444-449 CrossRef
6. Choi CS, Savage DB, Abu-Elheiga L et al (2007) Continuous fat oxidation in acetyl-CoA carboxylase 2 knockout mice increases total energy expenditure, reduces fat mass, and improves insulin sensitivity. Proc Natl Acad Sci U S A 104:16480-6485 CrossRef
7. Abu-Elheiga L, Oh W, Kordari P, Wakil SJ (2003) Acetyl-CoA carboxylase 2 mutant mice are protected against obesity and diabetes induced by high-fat/high-carbohydrate diets. Proc Natl Acad Sci U S A 100:10207-0212 CrossRef
8. Hoehn KL, Turner N, Swarbrick MM et al (2010) Acute or chronic upregulation of mitochondrial fatty acid oxidation has no net effect on whole-body energy expenditure or adiposity. Cell Metab 11:70-6 CrossRef
9. Olson DP, Pulinilkunnil T, Cline GW, Shulman GI, Lowell BB (2010) Gene knockout of Acc2 has little effect on body weight, fat mass, or food intake. Proc Natl Acad Sci U S A 107:7598-603 CrossRef
10. Dzamko N, Schertzer JD, Ryall JG et al (2008) AMPK-independent pathways regulate skeletal muscle fatty acid oxidation. J Physiol 586:5819-831 CrossRef
11. Jeppesen J, Maarbjerg SJ, Jordy AB et al (2013) LKB1 regulates lipid oxidation during exercise independently of AMPK. Diabetes
12. O'Neill HM, Maarbjerg SJ, Crane JD et al (2011) AMP-activated protein kinase (AMPK) beta1beta2 muscle null mice reveal an essential role for AMPK in maintaining mitochondrial content and glucose uptake during exercise. Proc Natl Acad Sci U S A 108:16092-6097 CrossRef
13. Steinberg GR, O'Neill HM, Dzamko NL et al (2010) Whole-body deletion of AMPK β2 reduces muscle AMPK and exercise capacity. J Biol Chem 285:37198-7209 CrossRef
14. Lee CW, Wong LL, Tse EY et al (2012) AMPK promotes p53 acetylation via phosphorylation and inactivation of SIRT1 in liver cancer cells. Cancer Res 72:4394-404 CrossRef
15. Fullerton MD, Galic S, Marcinko K et al (2013) Single phosphorylation sites in Acc1 and Acc2 regulate lipid homeostasis and the insulin-sensitizing effects of metformin. Nat Med 19:1649-654 CrossRef
16. Hawley SA, Fullerton MD, Ross FA et al (2012) The ancient drug salicylate directly activates AMP-activated protein kinase. Science 336:918-22 CrossRef
17. Galic S, Fullerton MD, Schertzer JD et al (2011) Hematopoietic AMPK beta1 reduces mouse adipose tissue macrophage inflammation and insulin resistance in obesity. J Clin Invest 121:4903-915 CrossRef
18. Palanivel R, Fullerton MD, Galic S et al (2012) Reduced Socs3 expression in adipose tissue protects female mice against obesity-induced insulin resistance. Diabetologia 55:3083-093 CrossRef
19. Passonneau JV, Gatfield PD, Schulz DW, Lowry OH (1967) An enzymic method for measurement of glycogen. Anal Biochem 19:315-26 CrossRef
20. Watt MJ, Dzamko N, Thomas WG et al (2006) CNTF reverses obesity-induced insulin resistance by activating skeletal muscle AMPK. Nat Med 12:541-48 CrossRef
21. Anderson EJ, Lustig ME, Boyle KE et al (2009) Mitochondrial H2O2 emission and cellular redox state link excess fat intake to insulin resistance in both rodents and humans. J Clin Invest 119:573-81 CrossRef
22. Smith BK, Jain SS, Rimbaud S et al (2011) FAT/CD36 is located on the outer mitochondrial membrane, upstream of long-chain acyl-CoA synthetase, and regulates palmitate oxidation. Biochem J 437:125-34 CrossRef
23. Bouzakri K, Austin R, Rune A et al (2008) Malonyl CoenzymeA decarboxylase regulates lipid and glucose metabolism in human skeletal muscle. Diabetes 57:1508-516 CrossRef
24. Joly E, Bendayan M, Roduit R, Saha AK, Ruderman NB, Prentki M (2005) Malonyl-CoA decarboxylase is present in the cytosolic, mitochondrial and peroxisomal compartments of rat hepatocytes. FEBS Lett 579:6581-586 CrossRef
25. Park H, Kaushik VK, Constant S et al (2002) Coordinate regulation of malonyl-CoA decarboxylase, sn-glycerol-3-phosphate acyltransferase, and acetyl-CoA carboxylase by AMP-activated protein kinase in rat tissues in response to exercise. J Biol Chem 277:32571-2577 CrossRef
26. Lowell BB, Shulman GI (2005) Mitochondrial dysfunction and type 2 diabetes. Science 307:384-87 CrossRef
27. Kerner J, Distler AM, Minkler P, Parland W, Peterman SM, Hoppel CL (2004) Phosphorylation of rat liver mitochondrial carnitine palmitoyltransferase-I: effect on the kinetic properties of the enzyme. J Biol Chem 279:41104-1113 CrossRef
28. Bezaire V, Heigenhauser GJ, Spriet LL (2004) Regulation of CPT I activity in intermyofibrillar and subsarcolemmal mitochondria from human and rat skeletal muscle. Am J Physiol Endocrinol Metab 286:E85–E91 CrossRef
29. Holloway GP, Bezaire V, Heigenhauser GJ et al (2006) Mitochondrial long chain fatty acid oxidation, fatty acid translocase/CD36 content and carnitine palmitoyltransferase I activity in human skeletal muscle during aerobic exercise. J Physiol 571:201-10 CrossRef
30. Holland WL, Brozinick JT, Wang LP et al (2007) Inhibition of ceramide synthesis ameliorates glucocorticoid-, saturated-fat-, and obesity-induced insulin resistance. Cell Metab 5:167-79 CrossRef
31. Hoehn KL, Hohnen-Behrens C, Cederberg A et al (2008) IRS1-independent defects define major nodes of insulin resistance. Cell Metab 7:421-33 CrossRef
32. JeBailey L, Wanono O, Niu W, Roessler J, Rudich A, Klip A (2007) Ceramide- and oxidant-induced insulin resistance involve loss of insulin-dependent Rac-activation and actin remodeling in muscle cells. Diabetes 56:394-03 CrossRef
33. Davies SP, Sim AT, Hardie DG (1990) Location and function of three sites phosphorylated on rat acetyl-CoA carboxylase by the AMP-activated protein kinase. Eur J Biochem 187:183-90 CrossRef
34. Munday MR, Campbell DG, Carling D, Hardie DG (1988) Identification by amino acid sequencing of three major regulatory phosphorylation sites on rat acetyl-CoA carboxylase. Eur J Biochem 175:331-38 CrossRef
35. Ha J, Daniel S, Broyles SS, Kim KH (1994) Critical phosphorylation sites for acetyl-CoA carboxylase activity. J Biol Chem 269:22162-2168
36. Corton JM, Gillespie JG, Hawley SA, Hardie DG (1995) 5-aminoimidazole-4-carboxamide ribonucleoside. A specific method for activating AMP-activated protein kinase in intact cells? Eur J Biochem 229:558-65 CrossRef
37. Thomson DM, Brown JD, Fillmore N et al (2007) LKB1 and the regulation of malonyl-CoA and fatty acid oxidation in muscle. Am J Physiol Endocrinol Metab 293:E1572–E1579 CrossRef
38. Kaushik VK, Young ME, Dean DJ, Kurowski TG, Saha AK, Ruderman NB (2001) Regulation of fatty acid oxidation and glucose metabolism in rat soleus muscle: effects of AICAR. Am J Physiol Endocrinol Metab 281:E335–E340
39. Merrill GF, Kurth EJ, Hardie DG, Winder WW (1997) AICA riboside increases AMP-activated protein kinase, fatty acid oxidation, and glucose uptake in rat muscle. Am J Physiol 273:E1107–E1112
40. Dzamko NL, Steinberg GR (2009) AMPK-dependent hormonal regulation of whole-body energy metabolism. Acta Physiol (Oxf) 196:115-27 CrossRef
41. Schenk S, Horowitz JF (2007) Acute exercise increases triglyceride synthesis in skeletal muscle and prevents fatty acid-induced insulin resistance. J Clin Invest 117:1690-698 CrossRef
42. Liu L, Zhang Y, Chen N, Shi X, Tsang B, Yu YH (2007) Upregulation of myocellular DGAT1 augments triglyceride synthesis in skeletal muscle and protects against fat-induced insulin resistance. J Clin Invest 117:1679-689 CrossRef
43. Ussher JR, Koves TR, Cadete VJ et al (2010) Inhibition of de novo ceramide synthesis reverses diet-induced insulin resistance and enhances whole-body oxygen consumption. Diabetes 59:2453-464 CrossRef
44. Pickersgill L, Litherland GJ, Greenberg AS, Walker M, Yeaman SJ (2007) Key role for ceramides in mediating insulin resistance in human muscle cells. J Biol Chem 282:12583-2589 CrossRef
45. Summers SA (2006) Ceramides in insulin resistance and lipotoxicity. Prog Lipid Res 45:42-2 CrossRef
46. Steinberg GR, Michell BJ, van Denderen BJ et al (2006) Tumor necrosis factor alpha-induced skeletal muscle insulin resistance involves suppression of AMP-kinase signaling. Cell Metab 4:465-74 CrossRef
47. Sugden MC, Howard RM, Munday MR, Holness MJ (1993) Mechanisms involved in the coordinate regulation of strategic enzymes of glucose metabolism. Adv Enzym Regul 33:71-5 CrossRef
48. Holness MJ, Kraus A, Harris RA, Sugden MC (2000) Targeted upregulation of pyruvate dehydrogenase kinase (PDK)-4 in slow-twitch skeletal muscle underlies the stable modification of the regulatory characteristics of PDK induced by high-fat feeding. Diabetes 49:775-81 CrossRef
49. Jeoung NH, Harris RA (2008) Pyruvate dehydrogenase kinase-4 deficiency lowers blood glucose and improves glucose tolerance in diet-induced obese mice. Am J Physiol Endocrinol Metab 295:E46–E54 CrossRef
50. Bandyopadhyay GK, Yu JG, Ofrecio J, Olefsky JM (2006) Increased malonyl-CoA levels in muscle from obese and type 2 diabetic subjects lead to decreased fatty acid oxidation and increased lipogenesis; thiazolidinedione treatment reverses these defects. Diabetes 55:2277-285 CrossRef - 作者单位：Hayley M. O’Neill (1) (2)
James S. Lally (1)
Sandra Galic (2)
Melissa Thomas (3)
Paymon D. Azizi (1)
Morgan D. Fullerton (1)
Brennan K. Smith (1) (5)
Thomas Pulinilkunnil (6)
Zhiping Chen (2)
M. Constantine Samaan (4)
Sebastian B. Jorgensen (2) (7)
Jason R. B. Dyck (6)
Graham P. Holloway (5)
Thomas J. Hawke (3)
Bryce J. van Denderen (2)
Bruce E. Kemp (2)
Gregory R. Steinberg (1) (2)
1. Division of Endocrinology and Metabolism, Department of Medicine, HSC 4N63, McMaster University, 1280 Main St West, Hamilton, ON, Canada, L8N 3Z5
2. St Vincent’s Institute of Medical Research and Department of Medicine, University of Melbourne, Fitzroy, VIC, Australia
3. Department of Pathology and Molecular Medicine, McMaster University, Hamilton, ON, Canada
5. Department of Human Health and Nutritional Sciences, University of Guelph, Guelph, ON, Canada
6. Cardiovascular Research Centre, Mazankowski Alberta Heart Institute, Department of Pediatrics, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, AB, Canada
4. Department of Paediatrics, McMaster University, Hamilton, ON, Canada
7. Diabetes Research Unit, Novo Nordisk A/S, Maaloev, Denmark - ISSN：1432-0428
文摘
Aims/hypothesis Obesity is characterised by lipid accumulation in skeletal muscle, which increases the risk of developing insulin resistance and type 2 diabetes. AMP-activated protein kinase (AMPK) is a sensor of cellular energy status and is activated in skeletal muscle by exercise, hormones (leptin, adiponectin, IL-6) and pharmacological agents (5-amino-4-imidazolecarboxamide ribonucleoside [AICAR] and metformin). Phosphorylation of acetyl-CoA carboxylase 2 (ACC2) at S221 (S212 in mice) by AMPK reduces ACC activity and malonyl-CoA content but the importance of the AMPK–ACC2–malonyl-CoA pathway in controlling fatty acid metabolism and insulin sensitivity is not understood; therefore, we characterised Acc2 S212A knock-in (ACC2 KI) mice. Methods Whole-body and skeletal muscle fatty acid oxidation and insulin sensitivity were assessed in ACC2 KI mice and wild-type littermates. Results ACC2 KI mice were resistant to increases in skeletal muscle fatty acid oxidation elicited by AICAR. These mice had normal adiposity and liver lipids but elevated contents of triacylglycerol and ceramide in skeletal muscle, which were associated with hyperinsulinaemia, glucose intolerance and skeletal muscle insulin resistance. Conclusions/interpretation These findings indicate that the phosphorylation of ACC2 S212 is required for the maintenance of skeletal muscle lipid and glucose homeostasis.