Carbenoxolone Treatment Ameliorated Metabolic Syndrome in WNIN/Ob Obese Rats, but Induced Severe Fat Loss and Glucose Intolerance in Lean Rats

PLoS ONE

Volumn 7, Issue 12, 2012, Pages

  Prasad Sakamuri, Siva Sankara Vara ^a,c   Sukapaka, Mahesh ^b,c   Prathipati, Vijay Kumar ^a   Nemani, Harishankar ^b   Putcha, Uday Kumar ^a   Pothana, Shailaja ^b   Koppala, Swarupa Rani ^a   Ponday, Lakshmi Raj Kumar ^a   Acharya, Vani ^a   Veetill, Giridharan Nappan ^b   Ayyalasomayajula, Vajreswari ^a  

^a NATIONAL INSTITUTE OF NUTRITION   (India)

^b INDIAN COUNCIL OF MEDICAL RESEARCH   (India)

^c TULANE UNIVERSITY SCHOOL OF MEDICINE   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

11BETA HYDROXYSTEROID DEHYDROGENASE 1; CARBENOXOLONE; CHOLESTEROL; GLYCOGEN; HORMONE; LIPID; TRIACYLGLYCEROL;

ADIPOCYTE HYPERTROPHY; ADIPOSE TISSUE; ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; ARTICLE; BODY COMPOSITION; BODY FAT DISTRIBUTION; COMORBIDITY; CONTROLLED STUDY; DISEASE ASSOCIATION; DISEASE SEVERITY; DRUG EFFICACY; ENZYME INHIBITION; FATTY LIVER; FIBROSIS; GENE EXPRESSION; GENETIC DISORDER; GENETIC OBESITY; GLUCOSE INTOLERANCE; HISTOPATHOLOGY; HORMONE BLOOD LEVEL; HYPERCHOLESTEROLEMIA; HYPERTRIGLYCERIDEMIA; HYPERTROPHY; INFLAMMATION; INSULIN RESISTANCE; LEAN BODY WEIGHT; LIPID BLOOD LEVEL; LIVER PARENCHYMA; MALE; METABOLIC SYNDROME X; MORNING DOSAGE; NONHUMAN; OBESITY; PHENOTYPE; RAT; RAT STRAIN; REVERSE TRANSCRIPTION POLYMERASE CHAIN REACTION; TISSUE LEVEL; TREATMENT DURATION; WNIN OB RAT;

11-BETA-HYDROXYSTEROID DEHYDROGENASE TYPE 1; ADIPOCYTES; ADIPOSE TISSUE; ADRENAL GLANDS; ANIMALS; BODY COMPOSITION; CARBENOXOLONE; CHOLESTEROL, HDL; CORTICOSTERONE; EATING; ENZYME INHIBITORS; FIBROSIS; GENE EXPRESSION REGULATION; GLUCOSE INTOLERANCE; GLYCOGEN; HYPERTROPHY; LIVER; MALE; METABOLIC SYNDROME X; OBESITY; ORGAN SIZE; RATS; SIGNAL TRANSDUCTION; THINNESS; TRIGLYCERIDES;

ANIMALIA; RATTUS;

EID: 84871327015     PISSN: None     EISSN: 19326203     Source Type: Journal    
DOI: 10.1371/journal.pone.0050216     Document Type: Article

References (38)

1. Rosmond R, Dallman MF, Bjorntorp P, (1998) Stress-related Cortisol secretion in men: relationships with abdominal obesity and endocrine, metabolic, and hemodynamic abnormalities. J Clin Endocrinol Metab 77: 1853-1859.
2. Tomlinson JW, Walker EA, Bujalska IJ, Draper N, Lavery GG, et al. (2004) 11beta-hydroxysteroid dehydrogenase type 1: A tissue-specific regulator of glucocorticoid response. Endo reviews 25: 831-866.
3. Draper N, Stewart PM, (2005) 11beta-hydroxysteroid dehydrogenase and the pre-receptor regulation of corticosteroid hormone action. J Endocrinol 186: 251-271.
4. Livingstone DEW, Jones GC, Smith K, Jamison PM, Andrew R, et al. (2000) Understanding the role of glucocorticoids in obesity: Tissue-specific alterations of corticosterone metabolism in obese zucker rats. Endocrinology 141: 560-563.
5. Rask E, Olsson T, Soderberg S, Andrew R, Livingstone DE, et al. (2001) Tissue-specific dysregualtion of cortisol metabolism in human obesity. J Clin Endocrinol Metab 86: 1418-1421.
6. Paulmyer-Lacroix O, Boullu S, Oliver C, Alessi MC, Grino M, (2002) Expression of the mRNA coding for 11beta-hydroxysteroid dehydrogenase type 1 in adipose tissue from obese patients: an in situ hybridization study. J Clin Endocrinol Metab 87: 2701-2705.
7. Masuzaki H, Paterson J, Shinyama H, Morton NM, Mullins JJ, et al. (2001) A transgenic model of visceral obesity and the metabolic syndrome. Science 294: 2166-2170.
8. Morton NM, Paterson JM, Masuzaki H, Holmes MC, Steals B, et al. (2004) Novel adipose tissue-mediated resistance to diet-induced visceral obesity in 11β-hydroxysteroid dehydrogenase type 1 deficient mice. Diabetes 53: 931-938.
9. Paterson JM, Morton NM, Fievet C, Kenyon CJ, Holmes MC, et al. (2004) Metabolic syndrome without obesity: hepatic overexpression of 11beta-hydroxysteroid dehydrogenase type 1 in transgenic mice. Proc Natl Acad Sci U S A 101: 7088-7093.
10. Livingstone DEW, Walker BR, (2003) Is 11β-Hydroxysteroid Dehydrogenase Type 1 a Therapeutic Target? Effects of Carbenoxolone in Lean and Obese Zucker rats. J Pharmcol Exp Ther 305: 167-172.
11. Nuotio-Antar AM, Hatchey DL, Hasty AH, (2007) Carbenoxolone treatment attenuates symptoms of metabolic syndrome and atherogenesis in obese, hyperlipidemic mice. Am J Physiol Endocrinol Metab 293: E1517-E1528.
12. Andrews RC, Rooyackers O, Walker BR, (2003) Effects of the 11β-hydroxysteroid dehydrogenase inhibitor carbenoxolone on insulin sensitivity in men with type 2 diabetes. J Clin Endocrinol Metab 88: 285-291.
13. Alberts P, Engblom L, Edling N, Forsgren M, Klingstrom G, et al. (2002) Selective inhibition of 11β-hydroxysteroid dehydrogenase type 1 decreases blood glucose concentrations in hyperglycemic mice. Diabetologia 45: 1528-1532 http://ajpendo.physiology.org/cgi/external_ref?access_num=10.1007%2Fs00125-002-0959-6&link_type=DOI.
14. Alberts P, Nilsson C, Selen G, Engblom LO, Edling NH, et al. (2003) Selective inhibition of 11β-hydroxysteroid dehydrogenase type 1 improves hepatic insulin sensitivity in hyperglycemic mice strains. Endocrinology 144: 4755-4762.
15. Berthiaume M, Laplante M, Festuccia W, Gelinas Y, Poulin S, et al. (2007) Depot-specific modulation of rat intra-abdominal adipose tissue lipid metabolism by pharmacologic inhibition of 11β-hydroxysteroid dehydrogenase type 1. Endocrinology 148: 2391-2397 http://ajpendo.physiology.org/cgi/ijlink?linkType=ABST&journalCode=endo&resid=148/5/2391.
16. Hermanowski-Vosatka A, Balkovec JM, Cheng K, Chen HY, Hernandez M, et al. (2005) 11ß-HSD1 inhibition ameliorates metabolic syndrome and prevents progression of atherosclerosis in mice. J Exp Med 202: 517-527.
17. Giridharan NV, Harishankar N, Satyavani M, (1996) A new rat model for the study of obesity. Scand J Lab Anim Sci 23: 131-137.
18. Prasad SS, Prashanth A, Kumar CP, Reddy SJ, Giridharan NV, et al. (2010) A Novel genetically-obese rat model with elevated 11beta-hydroxysteroid dehydrogenase type 1 activity in subcutaneous adipose tissue. Lipids Health Dis 9: 132.
19. Matthews JN, Altman DG, Cambell MJ, Royston P, (1990) Analysis serial measurements in medical research. Br Med J 300: 230-235.
20. Venu L, Harishankar N, Prasanna Krishna T, Raghunath M, (2004) Maternal dietary vitamin restriction increases body fat content but not insulin resistance in WNIN rat offspring up to 6 months of age. Diabetologia 47: 1493-1501.
21. Schoiswohl G, Schweiger M, Schreiber R, Gorkiewicz G, Preiss-Landl K, et al. (2010) Adipose tissue triglyceride lipase plays a key role in the supply of the working muscle with fatty acids. J Lipid Res 51: 490-499.
22. Folch J, Lees M, Stanley S, (1957) A simple method for the isolation and purification of lipids from animal tissues. J Biol Chem 226: 497-509.
23. Seckl JR, Morton NM, Chapman KE, Walker BR, (2004) Glucocorticoids and 11beta-hydroxysteroid dehydrogenase in adipose tissue. Recent Prog Horm Res 59: 359-393.
24. Berthiaume M, Laplante M, Festuccia WT, Cianflone K, Turcotte LP, et al. (2007) 11β-HSD1 inhibition improves triglyceridemia through reduced liver VLDL secretion and partitions lipids toward oxidative tissues. Am J Physiol Endocrinol metab 293: E1045-E1052.
25. Silver DL, Jiang XC, Tall AR, (1999) Increased High Density Lipoprotein (HDL), Detective Hepatic catabolism of ApoA-I and ApoA-II, and decreased Apo A-1 mRNA in ob/ob mice; Possible role of leptin in stimulation of HDL turnover. J Biol Chem 274: 4140-4146.
26. Jeyakumar SM, Vajreswari A, Giridharan NV, (2007) Impact of vitamin A on High-Density Lipoprotein-Cholesterol and Scavenger Receptor Class B1 in the obese rat. Obesity 15: 322-329.
27. Hauner H, Schmid P, Pfeiffer EF, (1987) Glucocorticoids and insulin promote the differentiation of human adipocyte precursor cells in to fat cells. J Clin Endocrinol Metab 64: 832-835.
28. Liu J, Wang L, Zhang A, Di W, Zhang X, et al. (2011) Adipose tissue-targeted 11β-hydroxysteroid dehydrogenase type 1 inhibitor protects against diet-induced obesity. Endocr J 58: 199-209.
29. Hadri KE, Charon C, Pairault J, Hauguel-de Mouzon S, Quignard-Boulange A, et al. (1997) Down-regulation of β3-adrenergic receptor expression in rat adipose tissue during the fasted/fed transition: evidence for a role of insulin. Biochem J 323: 359-364.
30. Kim H, Pennisi PA, Gavrilova O, Pack S, Jou W, et al. (2006) Effect of adipocyte β3-adrenergic receptor activation on the type 2 diabetic MKR mice. Am J Physiol Endo Metab 290: E1227-E1236.
31. Wamil M, Battle JH, Turban S, Kipari T, Seguret D, et al. (2011) Novel fat depot-specific mechanism underlie resistance to visceral obesity and inflammation in 11β- hydroxysteroid dehydrogenase type1-deficient mice. Diabetes 60: 1158-1167.
32. Khan T, Muise ES, Iyengar P, Wang ZV, Chandalia M, et al. (2009) Metabolic dysregulation and adipose tissue fibrosis: Role of Collagen IV. Mol Cell Biol 29: 1575-1591.
33. Farb MG, Bigornia S, Mott M, Tanriverdi K, Morin KM, et al. (2011) Reduced adipose tissue inflammation represents an intermediate cardiometabolic phenotype in obesity. J Am Coll Cardiol 58: 232-237.
34. Capel F, Klimca kova E, Viguerie N, Roussel B, Vítkova M, et al. (2009) Macrophages and adipocytes in human obesity. Diabetes 58: 1558-1567.
35. Wang Q, Somwar R, Bilan PJ, Liu Z, Jin J, et al. (1999) Protein Kinase B/Akt participates in GLUT 4 translocation by insulin in L6 Myoblasts. Mol. Cell. Biol 19: 4008-4018.
36. Xue B, Kim YB, Lee A, Toschi E, Bonner-Weir S, et al. (2007) Protein-tyrosine phosphatase 1B deficiency reduces insulin resistance and the diabetic phenotype in mice with polygenic insulin resistance. J Biol. Chem 282: 23829-40.
37. Koubi H, Duchamp C, Gelon A, Freminet A, Minaire Y, (1991) Resistance of hepatic glycogen to depletion in obese zucker rats. Can J Physiol pharmcol 69: 841-45.
38. Muller C, Assimacopoulos-Jeannet F, Mosimann F, Schneiter P, Riou JP, et al. (1997) Endogenous glucose production, gluconeogenesis and liver glycogen concentration in obese non- diabetic patients. Diabetologia 40: 463-468.