Horm Metab Res 2005; 37(7): 402-407
DOI: 10.1055/s-2005-870228
Original Basic
© Georg Thieme Verlag KG Stuttgart · New York

Effect of High-fat Diet on KKAy and ob/ob Mouse Liver and Adipose Tissue Corticosterone and 11-dehydrocorticosterone Concentrations

P.  Alberts1 , Y.  Rönquist-Nii1 , C.  Larsson1 , G.  Klingström1 , L.  Engblom1 , N.  Edling1 , V.  Lidell1 , I.  Berg1 , P.-O.  Edlund1 , M.  Ashkzari1 , N.  Sahaf1 , S.  Norling1 , V.  Berggren1 , K.  Bergdahl1 , M.  Forsgren1 , L.  Abrahmsén1
  • 1Department of Biology, Biovitrum, Stockholm, Sweden
Further Information

Publication History

Received 30 September 2004

Accepted after revision 15 February 2005

Publication Date:
21 July 2005 (online)

Abstract

The present study was performed to compare glucocorticoid levels in obese KKAy and ob/ob mice with those in normal C57BL/6J mice, and the effect of high-fat diet on glucocorticoids in KKAy and ob/ob mice. Liver, mesenteric and epididymal adipose tissue corticosterone and 11-dehydrocorticosterone concentrations as well as circulating corticosterone concentrations were measured. The KKAy and ob/ob mice displayed elevated serum corticosterone levels compared to normal mice, 2.0 to 2.8-fold in KKAy, and 11 to 16-fold in ob/ob mice. Liver corticosterone levels were 3.0 to 5.1 and 6.2 to 8.1-fold, and 11-dehydrocorticosterone levels were 3.4 to 3.6 and 6.7 to 8.2-fold higher in KKAy and ob/ob mice compared to normal mice. Mesenteric adipose tissue corticosterone levels were 2.7 to 4.2-fold higher, and 11-dehydrocorticosterone levels were 2 to 4-fold higher in ob/ob than in KKAy mice. Epididymal adipose tissue corticosterone levels were 3.0 to 6.2-fold higher, and 11-dehydrocorticosterone levels were 1.8 to 2.0-fold higher in ob/ob than in KKAy mice. Circulating, hepatic, and mesenteric and epididymal adipose tissue glucocorticoid concentrations were low in the normal C57BL/6J mouse, high in the ob/ob mouse, and intermediate in the KKAy mouse. 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) mRNA levels were doubled in ob/ob compared to KKAy mice in all three tissues. Glucocorticoid concentrations correlated with 11β-HSD1 mRNA levels. High-fat diet had no effect on the tissue glucocorticoid concentrations.

References

  • 1 Bray G A, York D A. Hypothalamic and genetic obesity in experimental animals: an autonomic and endocrine hypothesis.  Physiol Rev. 1979;  59 719-809
  • 2 Rask E, Olsson T, Söderberg S, Andrew R, Livingstone D E, Johnson O, Walker B R. Tissue-specific dysregulation of cortisol metabolism in human obesity.  J Clin Endocrinol Metab. 2001;  86 1418-1421
  • 3 La Fleur S E, Akana S F, Manalo S L, Dallman M F. Interaction between corticosterone and insulin in obesity: Regulation of lard intake and fat stores.  Endocrinology. 2004;  145 2174-2185
  • 4 Fehm H L, Born J, Peters A. Glucocorticoids and melanocortins in the regulation of body weight in humans.  Horm Metab Res. 2004;  36 360-364
  • 5 Parillo M, Riccardi G. Diet composition and the risk of type 2 diabetes: epidemiological and clinical evidence.  Br J Nutr. 2004;  92 7-19
  • 6 Collins S, Martin T L, Surwit R S, Robidoux J. Genetic vulnerability to diet-induced obesity in the C57BL/6J mouse: physiological and molecular characteristics.  Physiol Behav. 2004;  81 243-248
  • 7 Alberts P, Engblom L, Edling N, Forsgren M, Klingström G, Larsson C, Rönquist-Nii Y, Öhman B, Abrahmsén L. Selective inhibition of 11beta-hydroxysteroid dehydrogenase type 1 decreases blood glucose concentrations in hyperglycaemic mice.  Diabetologia. 2002;  45 1528-1532
  • 8 Barf T, Vallgarda J, Emond R, Häggström C, Kurz G, Nygren A, Larwood V, Mosialou E, Axelsson K, Olsson R, Engblom L, Edling N, Rönquist-Nii Y, Öhman B, Alberts P, Abrahmsén L. Arylsulfonamidothiazoles as a new class of potential antidiabetic drugs. Discovery of potent and selective inhibitors of the 11beta-hydroxysteroid dehydrogenase type 1.  J Med Chem. 2002;  45 3813-3815
  • 9 Alberts P, Nilsson C, Selén G, Engblom L OM, Edling N HM, Norling S, Klingström G, Larsson C, Forsgren M, Ashkzari M, Nilsson C E, Fiedler M, Bergqvist E, Öhman B, Björkstrand E, Abrahmsén L B. Selective inhibition of 11beta-hydroxysteroid dehydrogenase type 1 improves hepatic insulin sensitivity in hyperglycemic mice strains.  Endocrinology. 2003;  144 4755-4762
  • 10 Shackleton C HL. Mass spectrometry in the diagnosis of steroid-related disorders and in hypertension research.  J Steroid Biochem Mol Biol. 1993;  45 127-140
  • 11 Harris H J, Kotelevtsev Y, Mullins J J, Seckl J R, Holmes M C. Intracellular regeneration of glucocorticoids by 11beta-hydroxysteroid dehydrogenase (11beta-HSD)-1 plays a key role in regulation of the hypothalamic-pituitary-adrenal axis: Analysis of 11beta-HSD-1-deficient mice.  Endocrinology. 2001;  142 114-120
  • 12 Thupari J N, Kim E K, Moran T H, Ronnett G V, Kuhajda F P. Chronic C75 treatment of diet-induced obese mice increases fat oxidation and reduces food intake to reduce adipose mass.  J Physiol Endocrinol Metab. 2004;  287 E97-E104
  • 13 Dubuc P U, Ristimaki S, Cahn P J, Willis P L. Glucose tolerance in aging obese (ob/ob) and lean mice.  Horm Metab Res. 1983;  15 120-123
  • 14 Saito M, Bray G A. Diurnal rhythm for corticosterone in obese (ob/ob) diabetes (db/db) and gold-thioglucose-induced obesity in mice.  Endocrinology. 1983;  113 2181-2185
  • 15 Herberg L, Kley H K. Adrenal function and the effect of a high-fat diet on C57BL/6J and C57BL/6J-ob/ob mice.  Horm Metab Res. 1975;  7 410-415
  • 16 Dutta D, Sharma R. Regulation of hepatic glucocorticoid receptors in mice during dietary restriction.  Horm Metab Res. 2003;  35 415-420
  • 17 Seckl J R, Chapman K E. Medical and physiological aspects of the 11beta-hydroxysteroid dehydrogenase.  Eur J Biochem. 1997;  249 361-364
  • 18 Stewart P M, Krozowski Z S. 11Beta-Hydroxysteroid dehydrogenase.  Vitam Horm. 1999;  57 249-324
  • 19 Nobel S, Abrahmsén L, Oppermann U. Metabolic conversion as a pre-receptor control mechanism for lipophilic hormones.  Eur J Biochem. 2001;  268 4113-4125
  • 20 Masuzaki H, Paterson J, Shinyama H, Morton N M, Mullins J J, Seckl J R, Flier J S. A transgenic model of visceral obesity and the metabolic syndrome.  Science. 2001;  294 2166-2170
  • 21 Morton N M, Ramage L, Seckl J R. Down-regulation of adipose 11 beta-hydroxysteroid dehydrogenase type 1 by high-fat feeding in mice: A potential adaptive mechanism counteracting metabolic disease.  Endocrinology. 2004;  145 2707-2712
  • 22 Walker B R, Connacher A A, Lindsay R M, Webb D J, Edwards C R. Carbenoxolone increases hepatic insulin sensitivity in man: a novel role for 11-oxosteroid reductase in enhancing glucocorticoid receptor activation.  J Clin Endocrinol Metab. 1995;  80 3155-3159
  • 23 Walker B R, Seckl J R. 11Beta-hydroxysteroid dehydrogenase type 1 as a novel therapeutic target in metabolic and neurodegenerative disease.  Expert Op Therap Targets. 2003;  7 771-783
  • 24 Stulnig T M, Waldhäusl W. 11Beta-hydroxysteroid dehydrogenase type 1 in obesity and type 2 diabetes.  Diabetologia. 2004;  47 1-11
  • 25 Surwit R S, Wang S Y, Petro A E, Sanchis D, Raimbault S, Ricquier D, Collins S. Diet-induced changes in uncoupling proteins in obesity-prone and obesity-resistant strains of mice.  Proc Natl Acad Sci USA. 1998;  95 4061-4065
  • 26 Morton N M, Paterson J M, Masuzaki H, Holmes M C, Staels B, Fiévet C, Walker B R, Flier J S, Mullins J J, Seckl J R. Novel adipose tissue-mediated resistance to diet-induced visceral obesity in 11 beta-hydroxysteroid dehydrogenase type 1-deficient mice.  Diabetes. 2004;  53 931-938
  • 27 Liu Y, Nakagawa Y, Wang Y, Li R, Li X, Ohzeki T, Friedman T C. Leptin activation of corticosterone production in hepatocytes may contribute to the reversal of obesity and hyperglycemia in leptin-deficient ob/ob mice.  Diabetes. 2003;  52 1409-1416
  • 28 Draper N, Walker E A, Bujalska I J, Tomlinson J W, Chalder S M, Arlt W, Lavery G G, Bedendo O, Ray D W, Laing I, Malunowicz E, White P C, Hewison M, Mason P J, Connell J M, Shackleton C HL, Stewart P M. Mutations in the genes encoding 11beta-hydroxysteroid dehydrogenase type 1 and hexose-6-phosphate dehydrogenase interact to cause cortisone reductase deficiency.  Nature Gen. 2003;  34 434-439
  • 29 Tomlinson J W, Walker E A, Bujalska I J, Draper N, Lavery G G, Cooper M S, Hewison M, Stewart P M. 11beta-hydroxysteroid dehydrogenase type 1: a tissue-specific regulator of glucocorticoid response.  Endocrine Rev. 2004;  25 831-866

P. Alberts *

Pharmacology 2, Department of Biology

Biovitrum SE12 · SE 112 76 Stockholm · Sweden

* Present address: Affibody, Box 20137, SE-161 02 Bromma, Sweden

Phone: +46 (70) 322 3046 ·

Fax: +46 (8) 697 34 36

Email: peteris.alberts@biovitrum.com