Coenzyme A: Diacylglycerol acyltransferase 1 inhibitor ameliorates obesity, liver steatosis, and lipid metabolism abnormality in KKAy mice fed high-fat or high-carbohydrate diets

European Journal of Pharmacology

Volumn 640, Issue 1-3, 2010, Pages 243-249

  Yamamoto, Toshihiro ^a   Yamaguchi, Hiroshi ^a,b   Miki, Hiroshi ^a   Shimada, Mitsuyuki ^a   Nakada, Yoshihisa ^a   Ogino, Masaki ^a   Asano, Kouhei ^a   Aoki, Kazuko ^a   Tamura, Norikazu ^a   Masago, Minori ^a   Kato, Koki ^a  

^a TAKEDA PHARMACEUTICAL COMPANY LIMITED   (Japan)

^b UNIVERSITY OF THE RYUKYUS   (Japan)

Author keywords

Coenzyme A (CoA):diacylglycerol acyltransferase (DGAT); Diabetes; Hepatic steatosis; Hyperlipidemia; KKAy mice; Obesity

Indexed keywords

CHOLESTEROL; COENZYME A; DIACYLGLYCEROL ACYLTRANSFERASE 1; ENZYME INHIBITOR; FATTY ACID; N (5 BENZYL 4 PHENYL 1,3 THIAZOL 2 YL) 4 (4,5 DIETHOXY 2 METHYLPHENYL) 4 OXOBUTANAMIDE; TRIACYLGLYCEROL; UNCLASSIFIED DRUG; CARBOHYDRATE DIET; DIACYLGLYCEROL ACYLTRANSFERASE; FAT INTAKE;

ADIPOSE TISSUE; ANIMAL EXPERIMENT; ARTICLE; CARBOHYDRATE DIET; CATALYSIS; CHOLESTEROL BLOOD LEVEL; CHOLESTEROL LIVER LEVEL; CONTROLLED STUDY; DRUG STRUCTURE; FATTY ACID SYNTHESIS; FATTY LIVER; FEMALE; IC 50; LIPID DIET; LIPID LIVER LEVEL; LIPID METABOLISM; LIPID STORAGE; LOW FAT DIET; MALE; MOUSE; NONHUMAN; OBESITY; PRIORITY JOURNAL; SMALL INTESTINE; SYNTHESIS; TRIACYLGLYCEROL BLOOD LEVEL; ABSORPTION; ANIMAL; ANTAGONISTS AND INHIBITORS; BLOOD; DRUG EFFECTS; FAT INTAKE; LIVER; METABOLISM; TIME;

ABSORPTION; ADIPOSITY; ANIMALS; CHOLESTEROL; DIACYLGLYCEROL O-ACYLTRANSFERASE; DIETARY CARBOHYDRATES; DIETARY FATS; ENZYME INHIBITORS; FATTY LIVER; FEMALE; LIPID METABOLISM; LIVER; MALE; MICE; OBESITY; TIME FACTORS; TRIGLYCERIDES;

EID: 77953806507     PISSN: 00142999     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.ejphar.2010.04.050     Document Type: Article

References (24)

1. Abo-Hashema K.A.H., Cake M.H., Power G.W., Clarke D. Evidence for triacylglycerol synthesis in the lumen of microsomes via a lipolysis-esterification pathway involving carnitine acyltransferases. J. Biol. Chem. 1999, 274:35577-35582.
2. Birch A.M., Birtles S., Buckett L.K., Kemmitt P.D., Smith G.J., Smith T.J.D., Turnbull A.V., Wang S.J.Y. Discovery of a potent, selective, and orally efficacious pyrimidinooxazinyl bicyclooctaneacetic acid diacylglycerol acyltransferase-1 inhibitor. J. Med. Chem. 2009, 52:1558-1568.
3. Bligh E.G., Dyer W.J. A rapid method of total lipid extraction and purification. Can. J. Biochem. Physiol. 1959, 37:911-917.
4. Cases S., Smith S.J., Zheng Y.W., Myers H.M., Lear S.R., Sande E., Novak S., Colin C., Welch C.B., Lusis A.J., Erickson S.K., Farese R.V. Identification of a gene encoding an acyl CoA:diacylglycerol acyltransferase, a key enzyme in triacylglycerol synthesis. Proc. Natl Acad. Sci. USA 1998, 95:13018-13023.
5. Cases S., Stone S.J., Zhou P., Yen E., Tow B., Lardizabal K.D., Voelker T., Farese R.V. Cloning of DGAT2, a second mammalian diacylglycerol acyltransferase, and related family members. J. Biol. Chem. 2001, 276:38870-38876.
6. Chen H.C., Stone S.J., Zhou P., Buhman K.K., Farese R.V. Dissociation of obesity and impaired glucose disposal in mice overexpressing acyl coenzyme A:diacylglycerol acyltransferase 1 in white adipose tissue. Diabetes 2002, 51:3189-3195.
7. Inoue T., Node K. Statin therapy for vascular failure. Cardiovasc. Drugs Ther. 2007, 21:281-295.
8. Ip M.C.P., Draisey T.F., Thibert R.J., Gagneja G.L., Jasey G.M. Fetal lung maturity, as assessed by gas-liquid chromatographic determination of phospholipid palmitic acid in amniotic fluid. Clin. Chem. 1977, 23:35-40.
9. Iqbal J., Anwar K., Hussin M.M. Multiple, independently regulated pathways of cholesterol transport across the intestinal epithelial cells. J. Biol. Chem. 2003, 278:31610-31620.
10. King A.J., Segreti J.A., Larson K.J., Souers A.J., Kym P.R., Reilly R.M., Zhao G., Mittelstadt S.W., Cox B.F. Diacylglycerol acyltransferase 1 inhibition lowers serum triglycerides in the Zucker Fatty rat and the hyperlipidemic hamster. J. Pharmacol. Exp. Ther. 2009, 330:526-531.
11. Koga K., Kawashima S., Murakami M. In vitro and in situ evidence for the contribution of Labrasol and Gelucia 44/14 on transport of cephalexin and cefoperazone by rat intestine. Eur. J. Pharm. Biopharm. 2002, 64:82-88.
12. Nakada, Y., Ogino, M., Asano, K., Aoki, K., Miki, H., Yamamoto, T., Kato, K., Masago, M., Tamura, N., Shimada, M., 2010. Novel Acyl Coenzyme A: Diacylglycerol Acyltransferase 1 Inhibitors-Synthesis and Biological Activities of N-(Substituted heteroaryl)-4-(substituted phenyl)-4-oxobutanamides. Chem. Pharm. Bull. 58, 673-679.
13. Nishimoto T., Amano Y., Tozawa R., Ishikawa E., Imura Y., Yukimasa H., Sugiyama Y. Lipid-lowering properties of TAK-475, a squalene synthase inhibitor, in vivo and in vitro. Br. J. Pharmacol. 2003, 139:911-918.
14. Obici S., Feng Z., Arduino A., Conti R., Rossetti L. Inhibition of hypothalamic carnitine palmitoyltransferase-1 decreases food intake and glucose production. Nat. Med. 2003, 9:756-761.
15. Obici S., Feng Z., Morgan K., Stein D., Karkanias G., Rossetti L. Central administration of oleic acid inhibits glucose production and food intake. Diabetes 2002, 51:271-275.
16. Owen M.R., Corstorphine C.C., Zammit V.A. Overt and latent activities of diacylglycerol acyltransferase in rat liver microsomes: possible roles in very-low-density lipoprotein triacylglycerol secretion. Biochem. J. 1997, 323:17-21.
17. Park Y.B., Jeon S.M., Byun S.J., Kim H.S., Choi M.S. Absorption of intestinal free cholesterol is lowered by supplementation of Areca catechu L. extract in rats. Life Sci. 2002, 70:1849-1859.
18. Prasad Y.V., Puthli S.P., Eaimtrakarn S., Ishida M., Yoshikawa Y., Shibata N., Takeda K. Enhanced intestinal absorption of vancomycin with Labrasol and d-alpha-tocopheryl PEG 1000 succinate in rats. Int. J. Pharm. 2003, 250:181-190.
19. Smith S.J., Cases S., Jensen D.R., Chen H.C., Sande E., Tow B., Sanan D.A., Raber J., Eckel R.H., Farese R.V. Obesity resistance and multiple mechanisms of triglyceride synthesis in mice lacking Dgat. Nat. Genet. 2000, 25:87-90.
20. Stone S.J., Myers H.M., Watkins S.M., Brown B.E., Feingold K.R., Elias P.M., Farese R.V. Lipopenia and skin barrier abnormalities in DGAT2-deficient mice. J. Biol. Chem. 2004, 279:11767-11776.
21. Waterman I.J., Price N.T., Zammit V.A. Distinct ontogenic patterns of overt and latent DGAT activities of rat liver microsomes. J. Lipid Res. 2002, 43:1555-1562.
22. Yen C.L.E., Stone S.J., Koliwad S., Harris C., Farese R.V. DGAT enzymes and triacylglycerol biosynthesis. J. Lipid Res. 2008, 49:2283-2301.
23. Yu Y.H., Ginsberg H.N. The role of acyl-CoA:diacylglycerol acyltransferase (DGAT) in energy metabolism. Ann. Med. 2004, 36:252-261.
24. Zhao G., Souers A.J., Voorbach M., Falls H.D., Droz B., Brodjian S., Lau Y.Y., Iyengar R.R., Gao J., Judd A.S., Wagaw S.H., Ravn M.M., Engstrom K.M., Lynch J.K., Mulhern M.M., Freeman J., Dayton B.D., Wang X., Grihalde N., Fry D., Beno D.W., Marsh K.C., Su Z., Diaz G.J., Collins C.A., Sham H., Reilly R.M., Brune M.E., Kym P.R. Validation of diacyl glycerolacyltransferase I as a novel target for the treatment of obesity and dyslipidemia using a potent and selective small molecule inhibitor. J. Med. Chem. 2008, 51:380-383.