Therapeutic Inhibition of miR-33 Promotes Fatty Acid Oxidation but Does Not Ameliorate Metabolic Dysfunction in Diet-Induced Obesity

Arteriosclerosis, Thrombosis, and Vascular Biology

Volumn 35, Issue 12, 2015, Pages 2536-2543

  Karunakaran, Denuja ^a   Richards, Laura ^a   Geoffrion, Michele ^a   Barrette, Danyk ^a   Gotfrit, Ryan J ^a   Harper, Mary Ellen ^a   Rayner, Katey J ^a  

^a UNIVERSITY OF OTTAWA   (Canada)

Author keywords

Cholesterol; diet, high fat; microRNAs; obesity; therapeutics

Indexed keywords

ABC TRANSPORTER A1; ANTISENSE OLIGONUCLEOTIDE; CHOLESTEROL; FATTY ACID; INSULIN; MICRORNA; MICRORNA 33; STEROL REGULATORY ELEMENT BINDING PROTEIN 1; TRIACYLGLYCEROL; UNCLASSIFIED DRUG; ABCA1 PROTEIN, MOUSE; BIOLOGICAL MARKER; GLUCOSE BLOOD LEVEL; HADHB PROTEIN, MOUSE; HYDROXYMETHYLGLUTARYL COENZYME A REDUCTASE KINASE; MIRN33 MICRORNA, MOUSE; MITOCHONDRIAL TRIFUNCTIONAL PROTEIN BETA SUBUNIT;

ACC GENE; ADIPOSE TISSUE; AEROBIC METABOLISM; ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; ARTICLE; CHOLESTEROL BLOOD LEVEL; CONCENTRATION (PARAMETERS); CONTROLLED STUDY; DIET INDUCED OBESITY; FASN GENE; FATTY ACID OXIDATION; GENE; GENE EXPRESSION; GENE SILENCING; GENE TARGETING; INSULIN RESISTANCE; LIPID DIET; LIPID LIVER LEVEL; LUNG GAS EXCHANGE; MACROPHAGE; MALE; METABOLIC PARAMETERS; MOUSE; MOUSE MODEL; NONHUMAN; POLARIZATION; PRIORITY JOURNAL; TRIACYLGLYCEROL BLOOD LEVEL; WEIGHT GAIN; ANIMAL; BLOOD; C57BL MOUSE; DISEASE MODEL; GENETICS; GLUCOSE BLOOD LEVEL; LIVER; METABOLISM; OBESITY; OXIDATION REDUCTION REACTION; PHENOTYPE; TIME FACTOR;

ADIPOSE TISSUE; AMP-ACTIVATED PROTEIN KINASES; ANIMALS; ATP BINDING CASSETTE TRANSPORTER 1; BIOMARKERS; BLOOD GLUCOSE; CHOLESTEROL; DIET, HIGH-FAT; DISEASE MODELS, ANIMAL; FATTY ACIDS; INSULIN; INSULIN RESISTANCE; LIVER; MACROPHAGES; MALE; MICE, INBRED C57BL; MICRORNAS; MITOCHONDRIAL TRIFUNCTIONAL PROTEIN, BETA SUBUNIT; OBESITY; OLIGONUCLEOTIDES, ANTISENSE; OXIDATION-REDUCTION; PHENOTYPE; TIME FACTORS; TRIGLYCERIDES; WEIGHT GAIN;

EID: 84948120224     PISSN: 10795642     EISSN: 15244636     Source Type: Journal    
DOI: 10.1161/ATVBAHA.115.306404     Document Type: Article

References (30)

1. Alberti KG, Eckel RH, Grundy SM, Zimmet PZ, Cleeman JI, Donato KA, Fruchart JC, James WP, Loria CM, Smith SC Jr; International Diabetes Federation Task Force on Epidemiology and Prevention; Hational Heart, Lung, and Blood Institute; American Heart Association; World Heart Federation; International Atherosclerosis Society; International Association for the Study of Obesity. Harmonizing the metabolic syndrome: a joint interim statement of the International Diabetes Federation Task Force on Epidemiology and Prevention; National Heart, Lung, and Blood Institute; American Heart Association; World Heart Federation; International Atherosclerosis Society; and International Association for the Study of Obesity. Circulation. 2009;120:1640-1645. doi: 10.1161/CIRCULATIONAHA.109.192644.
2. Isomaa B, Almgren P, Tuomi T, Forsén B, Lahti K, Nissén M, Taskinen MR, Groop L. Cardiovascular morbidity and mortality associated with the metabolic syndrome. Diabetes Care. 2001;24:683-689.
3. Marquart TJ, Allen RM, Ory DS, Baldán A. miR-33 links SREBP-2 induction to repression of sterol transporters. Proc Natl Acad Sci USA. 2010;107:12228-12232. doi: 10.1073/pnas.1005191107.
4. Najafi-Shoushtari SH, Kristo F, Li Y, Shioda T, Cohen DE, Gerszten RE, Naär AM. MicroRNA-33 and the SREBP host genes cooperate to control cholesterol homeostasis. Science. 2010;328:1566-1569. doi: 10.1126/science.1189123.
5. Rayner KJ, Suárez Y, Dávalos A, Parathath S, Fitzgerald ML, Tamehiro N, Fisher EA, Moore KJ, Fernández-Hernando C. MiR-33 contributes to the regulation of cholesterol homeostasis. Science. 2010;328:1570-1573. doi: 10.1126/science.1189862.
6. Dávalos A, Goedeke L, Smibert P, et al. miR-33a/b contribute to the regulation of fatty acid metabolism and insulin signaling. Proc Natl Acad Sci USA. 2011;108:9232-9237. doi: 10.1073/pnas.1102281108.
7. Gerin I, Clerbaux LA, Haumont O, Lanthier N, Das AK, Burant CF, Leclercq IA, MacDougald OA, Bommer GT. Expression of miR-33 from an SREBP2 intron inhibits cholesterol export and fatty acid oxidation. J Biol Chem. 2010;285:33652-33661. doi: 10.1074/jbc.M110.152090.
8. Horie T, Ono K, Horiguchi M, Nishi H, Nakamura T, Nagao K, Kinoshita M, Kuwabara Y, Marusawa H, Iwanaga Y, Hasegawa K, Yokode M, Kimura T, Kita T. MicroRNA-33 encoded by an intron of sterol regulatory element-binding protein 2 (Srebp2) regulates HDL in vivo. Proc Natl Acad Sci USA. 2010;107:17321-17326. doi: 10.1073/pnas.1008499107.
9. Horie T, Baba O, Kuwabara Y, et al. MicroRNA-33 deficiency reduces the progression of atherosclerotic plaque in ApoE-/-mice. J Am Heart Assoc. 2012;1:e003376. doi: 10.1161/JAHA.112.003376.
10. Rayner KJ, Sheedy FJ, Esau CC, Hussain FN, Temel RE, Parathath S, van Gils JM, Rayner AJ, Chang AN, Suarez Y, Fernandez-Hernando C, Fisher EA, Moore KJ. Antagonism of miR-33 in mice promotes reverse cholesterol transport and regression of atherosclerosis. J Clin Invest. 2011;121:2921-2931. doi: 10.1172/JCI57275.
11. Rotllan N, Ramírez CM, Aryal B, Esau CC, Fernández-Hernando C. Therapeutic silencing of microRNA-33 inhibits the progression of atherosclerosis in Ldlr-/-mice-brief report. Arterioscler Thromb Vasc Biol. 2013;33:1973-1977. doi: 10.1161/ATVBAHA.113.301732.
12. Rayner KJ, Esau CC, Hussain FN, et al. Inhibition of miR-33a/b in nonhuman primates raises plasma HDL and lowers VLDL triglycerides. Nature. 2011;478:404-407. doi: 10.1038/nature10486.
13. Horie T, Nishino T, Baba O, et al. MicroRNA-33 regulates sterol regulatory element-binding protein 1 expression in mice. Nat Commun. 2013;4:2883. doi: 10.1038/ncomms3883.
14. van Rooij E, Olson EN. MicroRNA therapeutics for cardiovascular disease: opportunities and obstacles. Nat Rev Drug Discov. 2012;11:860-872. doi: 10.1038/nrd3864.
15. Collins S, Martin TL, Surwit RS, Robidoux J. Genetic vulnerability to diet-induced obesity in the C57BL/6J mouse: physiological and molecular characteristics. Physiol Behav. 2004;81:243-248. doi: 10.1016/j. physbeh.2004.02.006.
16. Wijesekara N, Zhang LH, Kang MH, Abraham T, Bhattacharjee A, Warnock GL, Verchere CB, Hayden MR. miR-33a modulates ABCA1 expression, cholesterol accumulation, and insulin secretion in pancreatic islets. Diabetes. 2012;61:653-658. doi: 10.2337/db11-0944.
17. Even PC, Nadkarni NA. Indirect calorimetry in laboratory mice and rats: principles, practical considerations, interpretation and perspectives. Am J Physiol Regul Integr Comp Physiol. 2012;303:R459-R476. doi: 10.1152/ajpregu.00137.2012.
18. Lumeng CN, Bodzin JL, Saltiel AR. Obesity induces a phenotypic switch in adipose tissue macrophage polarization. J Clin Invest. 2007;117:175-184. doi: 10.1172/JCI29881.
19. Weisberg SP, McCann D, Desai M, Rosenbaum M, Leibel RL, Ferrante AW Jr. Obesity is associated with macrophage accumulation in adipose tissue. J Clin Invest. 2003;112:1796-1808. doi: 10.1172/JCI19246.
20. Economou EK, Oikonomou E, Siasos G, Papageorgiou N, Tsalamandris S, Mourouzis K, Papaioanou S, Tousoulis D. The role of microRNAs in coronary artery disease: from pathophysiology to diagnosis and treatment. Atherosclerosis. 2015;241:624-633. doi: 10.1016/j.atherosclerosis.2015.06.037.
21. Goedeke L, Salerno A, Ramírez CM, Guo L, Allen RM, Yin X, Langley SR, Esau C, Wanschel A, Fisher EA, Suárez Y, Baldán A, Mayr M, Fernández-Hernando C. Long-term therapeutic silencing of miR-33 increases circulating triglyceride levels and hepatic lipid accumulation in mice. EMBO Mol Med. 2014;6:1133-1141. doi: 10.15252/emmm.201404046.
22. Geary RS. Antisense oligonucleotide pharmacokinetics and metabolism. Expert Opin Drug Metab Toxicol. 2009;5:381-391. doi: 10.1517/17425250902877680.
23. Fazio S, Linton MF. Mouse models of hyperlipidemia and atherosclerosis. Front Biosci. 2001;6:D515-D525.
24. Marquart TJ, Wu J, Lusis AJ, Baldán Á. Anti-miR-33 therapy does not alter the progression of atherosclerosis in low-density lipoprotein receptor-deficient mice. Arterioscler Thromb Vasc Biol. 2013;33:455-458. doi: 10.1161/ATVBAHA.112.300639.
25. Davis S, Propp S, Freier SM, Jones LE, Serra MJ, Kinberger G, Bhat B, Swayze EE, Bennett CF, Esau C. Potent inhibition of microRNA in vivo without degradation. Nucleic Acids Res. 2009;37:70-77. doi: 10.1093/nar/gkn904.
26. Galic S, Fullerton MD, Schertzer JD, Sikkema S, Marcinko K, Walkley CR, Izon D, Honeyman J, Chen ZP, van Denderen BJ, Kemp BE, Steinberg GR. Hematopoietic AMPK 1 reduces mouse adipose tissue macrophage inflammation and insulin resistance in obesity. J Clin Invest. 2011;121:4903-4915. doi: 10.1172/JCI58577.
27. Andrikopoulos S, Blair AR, Deluca N, Fam BC, Proietto J. Evaluating the glucose tolerance test in mice. Am J Physiol Endocrinol Metab. 2008;295:E1323-E1332. doi: 10.1152/ajpendo.90617.2008.
28. Heijboer AC, Donga E, Voshol PJ, Dang ZC, Havekes LM, Romijn JA, Corssmit EP. Sixteen hours of fasting differentially affects hepatic and muscle insulin sensitivity in mice. J Lipid Res. 2005;46:582-588. doi: 10.1194/jlr.M400440-JLR200.
29. Allen RM, Marquart TJ, Albert CJ, Suchy FJ, Wang DQ, Ananthanarayanan M, Ford DA, Baldán A. miR-33 controls the expression of biliary transporters, and mediates statin-and diet-induced hepatotoxicity. EMBO Mol Med. 2012;4:882-895. doi: 10.1002/emmm.201201228.
30. Rottiers V, Obad S, Petri A, et al. Pharmacological inhibition of a microRNA family in nonhuman primates by a seed-targeting 8-mer antimiR. Sci Transl Med. 2013;5:212ra162. doi: 10.1126/scitranslmed.3006840.