Inhibition of Acetyl-CoA carboxylase 2 enhances skeletal muscle fatty acid oxidation and improves whole-body glucose homeostasis in db/db mice

Diabetologia

Volumn 55, Issue 7, 2012, Pages 2044-2053

  Glund, S ^a   Schoelch, C ^a   Thomas, L ^a   Niessen, H G ^a   Stiller, D ^a   Roth, G J ^a   Neubauer, H ^a  

^a BOEHRINGER INGELHEIM PHARMA GMBH AND CO KG   (Germany)

Author keywords

Diabetes; IMCL; Intramyocellular lipid; Metabolic flexibility; Muscle lipid; Pharmacological inhibitor

Indexed keywords

ACETYL COENZYME A CARBOXYLASE; ACETYL COENZYME A CARBOXYLASE 2; ACETYL COENZYME A CARBOXYLASE 2 INHIBITOR; ENZYME INHIBITOR; FATTY ACID; FLUORODEOXYGLUCOSE F 18; GLUCOSE; HEMOGLOBIN A1C; INSULIN; MALONYL COENZYME A; PIOGLITAZONE; TRIACYLGLYCEROL; UNCLASSIFIED DRUG;

ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; ARTICLE; BODY WEIGHT; CONTROLLED STUDY; DIABETES MELLITUS; DRUG EFFECT; ENZYME INHIBITION; EXTENSOR DIGITORUM LONGUS MUSCLE; FATTY ACID OXIDATION; GLUCOSE HOMEOSTASIS; IN VITRO STUDY; IN VIVO STUDY; INSULIN BLOOD LEVEL; MALE; MOUSE; NONHUMAN; NUCLEOTIDE SEQUENCE; OBESITY; ORAL GLUCOSE TOLERANCE TEST; PRIORITY JOURNAL; SKELETAL MUSCLE;

ACETYL-COA CARBOXYLASE; ANIMALS; BODY WEIGHT; FATTY ACIDS; GLUCOSE; HEMOGLOBIN A, GLYCOSYLATED; HOMEOSTASIS; INSULIN RESISTANCE; MALE; MALONYL COENZYME A; MICE; MICE, INBRED NOD; MUSCLE, SKELETAL; OBESITY; TRIGLYCERIDES;

EID: 84866391983     PISSN: 0012186X     EISSN: 14320428     Source Type: Journal    
DOI: 10.1007/s00125-012-2554-9     Document Type: Article

References (39)

1. Hulver MW, Berggren JR, Cortright RN et al (2003) Skeletal muscle lipid metabolism with obesity. Am J Physiol Endocrinol Metab 284:E741-E747
2. Kim JY, Hickner RC, Cortright RL, Dohm GL, Houmard JA (2000) Lipid oxidation is reduced in obese human skeletal muscle. Am J Physiol Endocrinol Metab 279:E1039-E1044
3. Neumann-Haefelin C, Kuhlmann J, Belz U et al (2003) Determinants of intramyocellular lipid concentrations in rat hind-leg muscle. Magn Reson Med 50:242-248
4. Savage DB, Petersen KF, Shulman GI (2007) Disordered lipid metabolism and the pathogenesis of insulin resistance. Physiol Rev 87:507-520
5. Dobbins RL, Szczepaniak LS, Bentley B, Esser V, Myhill J, McGarry JD (2001) Prolonged inhibition of muscle carnitine palmitoyltransferase-1 promotes intramyocellular lipid accumulation and insulin resistance in rats. Diabetes 50:123-130
6. Krssak M, Falk PK, Dresner A et al (1999) Intramyocellular lipid concentrations are correlated with insulin sensitivity in humans: a 1H NMR spectroscopy study. Diabetologia 42:113-116
7. Jacob S, Machann J, Rett K et al (1999) Association of increased intramyocellular lipid content with insulin resistance in lean non-diabetic offspring of type 2 diabetic subjects. Diabetes 48:1113-1119
8. Lara-Castro C, Newcomer BR, Rowell J et al (2008) Effects of short-term very low-calorie diet on intramyocellular lipid and insulin sensitivity in nondiabetic and type 2 diabetic subjects. Metabolism 57:1-8
9. Wakil SJ, Abu-Elheiga LA (2009) Fatty acid metabolism: target for metabolic syndrome. J Lipid Res 50(Suppl):S138-S143
10. Kim CW, Moon YA, Park SW, Cheng D, Kwon HJ, Horton JD (2010) Induced polymerization of mammalian acetyl-CoA carboxylase by MIG12 provides a tertiary level of regulation of fatty acid synthesis. Proc Natl Acad Sci USA 107:9626-9631
11. Schreurs M, Kuipers F, van der Leij FR (2010) Regulatory enzymes of mitochondrial beta-oxidation as targets for treatment of the metabolic syndrome. Obes Rev 11:380-388
12. Witters LA, Watts TD, Daniels DL, Evans JL (1988) Insulin stimulates the dephosphorylation and activation of acetyl-CoA carboxylase. Proc Natl Acad Sci USA 85:5473-5477
13. Carling D, Clarke PR, Zammit VA, Hardie DG (1989) Purification and characterization of the AMP-activated protein kinase. Copurification of acetyl-CoA carboxylase kinase and 3-hydroxy-3-methylglutaryl-CoA reductase kinase activities. Eur J Biochem 186:129-136
14. Abu-Elheiga L, Matzuk MM, bo-Hashema KA, Wakil SJ (2001) Continuous fatty acid oxidation and reduced fat storage in mice lacking acetyl-CoA carboxylase 2. Science 291:2613-2616
15. 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 11:70-76
16. 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 USA 107:7598-7603
17. Harwood HJ Jr, Petras SF, Shelly LD et al (2003) Isozyme-nonselective N-substituted bipiperidylcarboxamide acetyl-CoA carboxylase inhibitors reduce tissue malonyl-CoA concentrations, inhibit fatty acid synthesis, and increase fatty acid oxidation in cultured cells and in experimental animals. J Biol Chem 278:37099-37111
18. Keil S, Muller M, Zoller G et al (2010) Identification and synthesis of novel inhibitors of acetyl-CoA carboxylase with in vitro and in vivo efficacy on fat oxidation. J Med Chem 53:8679-8687
19. Kreuz S, Schoelch C, Thomas L, Rist W, Rippmann JF, Neubauer H (2009) Acetyl-CoA carboxylases 1 and 2 show distinct expression patterns in rats and humans and alterations in obesity and diabetes. Diabetes Metab Res Rev 25:577-586
20. Rosa G, Manco M, Vega N et al (2003) Decreased muscle acetyl-coenzyme A carboxylase 2 mRNA and insulin resistance in formerly obese subjects. Obes Res 11:1306-1312
21. Jans A, Sparks LM, van Hees AM et al (2011) Transcriptional metabolic inflexibility in skeletal muscle among individuals with increasing insulin resistance. Obesity (Silver Spring) 19:2158-2166
22. 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 USA 100:10207-10212
23. 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 USA 104:16480-16485
24. Oh W, Abu-Elheiga L, Kordari P et al (2005) Glucose and fat metabolism in adipose tissue of acetyl-CoA carboxylase 2 knockout mice. Proc Natl Acad Sci USA 102:1384-1389
25. Chadt A, Leicht K, Deshmukh A et al (2008) Tbc1d1 mutation in lean mouse strain confers leanness and protects from diet-induced obesity. Nat Genet 40:1354-1359
26. Gu YG, Weitzberg M, Clark RF et al (2006) Synthesis and structure-activity relationships of N-{3-[2-(4-alkoxyphenoxy) thia-zol-5-yl]-1-methylprop-2-ynyl}carboxy derivatives as selective acetyl-CoA carboxylase 2 inhibitors. J Med Chem 49:3770-3773
27. Gu YG, Weitzberg M, Clark RF et al (2007) N-{3-[2-(4-alkoxy-phenoxy) thiazol-5-yl]-1-methylprop-2-ynyl}carboxy derivatives as acetyl-coA carboxylase inhibitors-improvement of cardiovascular and neurological liabilities via structural modifications. J Med Chem 50:1078-1082
28. Neumaier M, Niessen HG, Kaulisch T, Stiller D (2009) Inductively coupled Helmholtz coil on a dedicated imaging platform for the in vivo 1H-MRS measurement of intramyocellular lipids in the hind leg of rats. Magn Reson Med 62:1036-1041
29. Provencher SW (1993) Estimation of metabolite concentrations from localized in vivo proton NMR spectra. Magn Reson Med 30:672-679
30. Skoch A, Jiru F, Dezortova M et al (2006) Intramyocellular lipid quantification from 1H long echo time spectra at 1.5 and 3 T by means of the LC model technique. J Magn Reson Imaging 23:728-735
31. Torriani M, Thomas BJ, Halpern EF, Jensen ME, Rosenthal DI, Palmer WE (2005) Intramyocellular lipid quantification: repeatability with 1H MR spectroscopy. Radiology 236:609-614
32. Patlak CS, Blasberg RG, Fenstermacher JD (1983) Graphical evaluation of blood-to-brain transfer constants from multiple-time uptake data. J Cereb Blood Flow Metab 3:1-7
33. Fissoune R, Janier M, Briguet A, Hiba B (2009) In vivo assessment of mouse hindleg intramyocellular lipids by 1H-MR spec-troscopy. Acad Radiol 16:890-896
34. Morino K, Petersen KF, Shulman GI (2006) Molecular mechanisms of insulin resistance in humans and their potential links with mitochondrial dysfunction. Diabetes 55(Suppl 2):S9-S15
35. Hallakou S, Doare L, Foufelle F et al (1997) Pioglitazone induces in vivo adipocyte differentiation in the obese Zucker fa/fa rat. Diabetes 46:1393-1399
36. Kelley DE, Goodpaster B, Wing RR, Simoneau JA (1999) Skeletal muscle fatty acid metabolism in association with insulin resistance, obesity, and weight loss. Am J Physiol 277:E1130-E1141
37. Kelley DE (2002) Skeletal muscle triglycerides: an aspect of regional adiposity and insulin resistance. Ann N Y Acad Sci 967:135-145
38. Schreurs M, van Dijk TH, Gerding A, Havinga R, Reijngoud DJ, Kuipers F (2009) Soraphen, an inhibitor of the acetyl-CoA car-boxylase system, improves peripheral insulin sensitivity in mice fed a high-fat diet. Diabetes Obes Metab 11:987-991
39. Castle JC, Hara Y, Raymond CK et al (2009) ACC2 is expressed at high levels in human white adipose and has an isoform with a novel N-terminus [corrected]. PLoS One 4:e4369