Antiobesity effect of a small molecule repressor of RORγ

Molecular Pharmacology

Volumn 88, Issue 1, 2015, Pages 48-56

  Chang, Mi Ra ^a   He, Yuanjun ^a   Khan, Tanya M ^a   Kuruvilla, Dana S ^a   Garcia Ordonez, Ruben ^a   Corzo, Cesar A ^a   Unger, Thaddeus J ^b   White, David W ^b   Khan, Susan ^a   Lin, Li ^a   Cameron, Michael D ^a   Kamenecka, Theodore M ^a   Griffin, Patrick R ^a  

^a SCRIPPS RESEARCH INSTITUTE   (United States)

^b Ember Therapeutics   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

1 [4 [[4' (1,1,1,3,3,3 HEXAFLUORO 2 HYDROXYPROPAN 2 YL) (1,1' BIPHENYL) 4 YL]METHYL]PIPERAZINE 1 YL]ETHANONE; ADIPONECTIN; ANTIOBESITY AGENT; FIBROBLAST GROWTH FACTOR 21; HORMONE SENSITIVE LIPASE; ORPHAN NUCLEAR RECEPTOR; UNCLASSIFIED DRUG; ADIPOQ PROTEIN, MOUSE; BIPHENYL DERIVATIVE; FIBROBLAST GROWTH FACTOR; INSULIN; PIPERAZINE DERIVATIVE; RETINOID RELATED ORPHAN RECEPTOR GAMMA; RORC PROTEIN, MOUSE; SR1555;

ANIMAL CELL; ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; ARTICLE; BODY WEIGHT; CELL CULTURE; CONTROLLED STUDY; DIET INDUCED OBESITY; DRUG BLOOD LEVEL; ENZYME ACTIVITY; EX VIVO STUDY; FAT MASS; FATTY ACID OXIDATION; FOOD INTAKE; GENE; INSULIN SENSITIVITY; LIPID STORAGE; MALE; MOUSE; NON INSULIN DEPENDENT DIABETES MELLITUS; NONHUMAN; PRIORITY JOURNAL; PROADIPOCYTE; PROTEIN EXPRESSION; THERMOGENESIS; 3T3 CELL LINE; ADIPOGENESIS; ANIMAL; ANTAGONISTS AND INHIBITORS; CHEMICALLY INDUCED; DRUG EFFECTS; GENETICS; LIPID DIET; METABOLISM; OBESITY; SYNTHESIS;

3T3-L1 CELLS; ADIPOGENESIS; ADIPONECTIN; ANIMALS; ANTI-OBESITY AGENTS; BIPHENYL COMPOUNDS; BODY WEIGHT; CELLS, CULTURED; DIET, HIGH-FAT; FIBROBLAST GROWTH FACTORS; INSULIN; MALE; MICE; NUCLEAR RECEPTOR SUBFAMILY 1, GROUP F, MEMBER 3; OBESITY; PIPERAZINES;

EID: 84940208724     PISSN: 0026895X     EISSN: 15210111     Source Type: Journal    
DOI: 10.1124/mol.114.097485     Document Type: Article

References (36)

1. Barish GD, Downes M, Alaynick WA, Yu RT, Ocampo CB, Bookout AL, Mangelsdorf DJ, and Evans RM (2005) A Nuclear Receptor Atlas: macrophage activation. Mol Endocrinol 19:2466-2477.
2. Becker-André M, André E, and DeLamarter JF (1993) Identification of nuclear receptor mRNAs by RT-PCR amplification of conserved zinc-finger motif sequences. Biochem Biophys Res Commun 194:1371-1379.
3. Bhat PK, Navin HK, Idris M, Christopher P, and Rai N (2014) Modified distal shoe appliance for premature loss of multiple deciduous molars: A case report. J Clin Diagn Res 8:ZD43-ZD45.
4. Bouchard C (1988) Genetic factors in the regulation of adipose tissue distribution. Acta Med Scand Suppl 723:135-141.
5. Chang MR, Lyda B, Kamenecka TM, and Griffin PR (2014) Pharmacologic repression of retinoic acid receptor-related orphan nuclear receptor γ is therapeutic in the collagen-induced arthritis experimental model. Arthritis Rheum (Munch) 66:579-588.
6. Claus TH, Lowe DB, Liang Y, Salhanick AI, Lubeski CK, Yang L, Lemoine L, Zhu J, and Clairmont KB (2005) Specific inhibition of hormone-sensitive lipase improves lipid profile while reducing plasma glucose. J Pharmacol Exp Ther 315:1396-1402.
7. DeFuria J, Belkina AC, Jagannathan-Bogdan M, Snyder-Cappione J, Carr JD, Nersesova YR, Markham D, Strissel KJ, Watkins AA, and Zhu M et al. (2013) B cells promote inflammation in obesity and type 2 diabetes through regulation of T-cell function and an inflammatory cytokine profile. Proc Natl Acad Sci USA 110:5133-5138.
8. Eller K, Kirsch A, Wolf AM, Sopper S, Tagwerker A, Stanzl U, Wolf D, Patsch W, Rosenkranz AR, and Eller P (2011) Potential role of regulatory T cells in reversing obesity-linked insulin resistance and diabetic nephropathy. Diabetes 60:2954-2962.
9. Giguère V, Tini M, Flock G, Ong E, Evans RM, and Otulakowski G (1994) Isoform-specific amino-terminal domains dictate DNA-binding properties of RORα, a novel family of orphan hormone nuclear receptors. Genes Dev 8:538-553.
10. Girousse A, Tavernier G, Valle C, Moro C, Mejhert N, Dinel AL, Houssier M, Roussel B, Besse-Patin A, and Combes M et al. (2013) Partial inhibition of adipose tissue lipolysis improves glucose metabolism and insulin sensitivity without alteration of fat mass. PLoS Biol 11:e1001485.
11. Grundy SM, Cleeman JI, Daniels SR, Donato KA, Eckel RH, Franklin BA, Gordon DJ, Krauss RM, Savage PJ, and Smith SC, Jr et al. American Heart Association; National Heart, Lung, and Blood Institute (2005) Diagnosis and management of the metabolic syndrome: an American Heart Association/National Heart, Lung, and Blood Institute Scientific Statement. Circulation 112:2735-2752.
12. Grundy SM, Hansen B, Smith SC, Jr, Cleeman JI, and Kahn RA American Heart Association; National Heart, Lung, and Blood Institute; American Diabetes Association (2004) Clinical management of metabolic syndrome: report of the American Heart Association/National Heart, Lung, and Blood Institute/American Diabetes Association conference on scientific issues related to management. Circulation 109:551-556.
13. Gu Y, Yang J, Ouyang X, Liu W, Li H, Yang J, Bromberg J, Chen SH, Mayer L, and Unkeless JC et al. (2008) Interleukin 10 suppresses Th17 cytokines secreted by macrophages and T cells. Eur J Immunol 38:1807-1813.
14. Huh JR, Leung MW, Huang P, Ryan DA, Krout MR, Malapaka RR, Chow J, Manel N, Ciofani M, and Kim SV et al. (2011) Digoxin and its derivatives suppress TH17 cell differentiation by antagonizing RORgt activity. Nature 472:486-490.
15. Jetten AM (2009) Retinoid-related orphan receptors (RORs): critical roles in development, immunity, circadian rhythm, and cellular metabolism. Nucl Recept Signal 7:e003.
16. Kliewer SA, Lehmann JM, and Willson TM (1999) Orphan nuclear receptors: shifting endocrinology into reverse. Science 284:757-760.
17. Koh YJ, Kang S, Lee HJ, Choi TS, Lee HS, Cho CH, and Koh GY (2007) Bone marrow-derived circulating progenitor cells fail to transdifferentiate into adipocytes in adult adipose tissues in mice. J Clin Invest 117:3684-3695.
18. Kojetin DJ and Burris TP (2014) REV-ERB and ROR nuclear receptors as drug targets. Nat Rev Drug Discov 13:197-216.
19. Kumar N, Kojetin DJ, Solt LA, Kumar KG, Nuhant P, Duckett DR, Cameron MD, Butler AA, Roush WR, and Griffin PR et al. (2011) Identification of SR3335 (ML-176): a synthetic RORα selective inverse agonist. ACS Chem Biol 6:218-222.
20. Kumar N, Lyda B, Chang MR, Lauer JL, Solt LA, Burris TP, Kamenecka TM, and Griffin PR (2012) Identification of SR2211: a potent synthetic RORγ-selective modulator. ACS Chem Biol 7:672-677.
21. Kumar N, Solt LA, Conkright JJ, Wang Y, Istrate MA, Busby SA, Garcia-Ordonez RD, Burris TP, and Griffin PR (2010) The benzenesulfoamide T0901317 [N-(2,2,2-trifluoroethyl)-N-[4-[2,2,2-trifluoro-1-hydroxy-1-(trifluoromethyl)ethyl]phenyl]-benzenesulfonamide] is a novel retinoic acid receptor-related orphan receptor-α/γ inverse agonist. Mol Pharmacol 77:228-236.
22. Large V, Arner P, Reynisdottir S, Grober J, Van Harmelen V, Holm C, and Langin D (1998) Hormone-sensitive lipase expression and activity in relation to lipolysis in human fat cells. J Lipid Res 39:1688-1695.
23. Marciano DP, Chang MR, Corzo CA, Goswami D, Lam VQ, Pascal BD, and Griffin PR (2014) The therapeutic potential of nuclear receptor modulators for treatment of metabolic disorders: PPARg, RORs, and Rev-erbs. Cell Metab 19:193-208.
24. Meissburger B, Ukropec J, Roeder E, Beaton N, Geiger M, Teupser D, Civan B, Langhans W, Nawroth PP, and Gasperikova D et al. (2011) Adipogenesis and insulin sensitivity in obesity are regulated by retinoid-related orphan receptor gamma. EMBO Mol Med 3:637-651.
25. + T cell subsets. J Immunol 186:3299-3303.
26. Moller DE, Bjørbaek C, and Vidal-Puig A (1996) Candidate genes for insulin resistance. Diabetes Care 19:396-400.
27. Moller DE and Kaufman KD (2005) Metabolic syndrome: a clinical and molecular perspective. Annu Rev Med 56:45-62.
28. Ohno H, Shinoda K, Spiegelman BM, and Kajimura S (2012) PPARg agonists induce a white-to-brown fat conversion through stabilization of PRDM16 protein. Cell Metab 15:395-404.
29. Rothwell NJ and Stock MJ (1997) A role for brown adipose tissue in diet-induced thermogenesis. Obes Res 5:650-656.
30. H17 cells and stimulates T regulatory cells. ACS Chem Biol 7:1515-1519.
31. H17 differentiation and autoimmunity by a synthetic ROR ligand. Nature 472:491-494.
32. Takeda Y, Kang HS, Freudenberg J, DeGraff LM, Jothi R, and Jetten AM (2014) Retinoic acid-related orphan receptor γ (RORγ): a novel participant in the diurnal regulation of hepatic gluconeogenesis and insulin sensitivity. PLoS Genet 10:e1004331.
33. Tataranni PA and Ortega E (2005) A burning question: does an adipokine-induced activation of the immune system mediate the effect of overnutrition on type 2 diabetes? Diabetes 54:917-927.
34. Wang Y, Kumar N, Nuhant P, Cameron MD, Istrate MA, Roush WR, Griffin PR, and Burris TP (2010) Identification of SR1078, a synthetic agonist for the orphan nuclear receptors RORα and RORγ. ACS Chem Biol 5:1029-1034.
35. Wu J, Boström P, Sparks LM, Ye L, Choi JH, Giang AH, Khandekar M, Virtanen KA, Nuutila P, and Schaart G et al. (2012) Beige adipocytes are a distinct type of thermogenic fat cell in mouse and human. Cell 150:366-376.
36. Wu J, Cohen P, and Spiegelman BM (2013) Adaptive thermogenesis in adipocytes: is beige the new brown? Genes Dev 27:234-250.