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Horm Metab Res 2012; 44(01): 15-20
DOI: 10.1055/s-0031-1297990
Original Basic
© Georg Thieme Verlag KG Stuttgart · New York

Carbenoxolone Alters the Morphology of Adipose Tissues and Downregulates Genes Involved in Adipogenesis, Glucose Transport and Lipid Metabolism in High-Fat Diet-fed Mice

S. Sano
1   Department of Pediatrics, Hamamatsu University School of Medicine, Hamamatsu, Shizuoka, Japan
,
Y. Nakagawa
1   Department of Pediatrics, Hamamatsu University School of Medicine, Hamamatsu, Shizuoka, Japan
,
R. Yamaguchi
1   Department of Pediatrics, Hamamatsu University School of Medicine, Hamamatsu, Shizuoka, Japan
,
Y. Fujisawa
1   Department of Pediatrics, Hamamatsu University School of Medicine, Hamamatsu, Shizuoka, Japan
,
E. Satake
1   Department of Pediatrics, Hamamatsu University School of Medicine, Hamamatsu, Shizuoka, Japan
,
E. Nagata
1   Department of Pediatrics, Hamamatsu University School of Medicine, Hamamatsu, Shizuoka, Japan
,
T. Nakanishi
1   Department of Pediatrics, Hamamatsu University School of Medicine, Hamamatsu, Shizuoka, Japan
,
Y.-J. Liu
2   Division of Endocrinology, Metabolism and Molecular Medicine, UCLA School of Medicine, The Charles Drew University of Medicine and Science, Los Angeles, California, USA
,
T. Ohzeki
1   Department of Pediatrics, Hamamatsu University School of Medicine, Hamamatsu, Shizuoka, Japan
› Author Affiliations
Further Information

Publication History

received 18 April 2011

accepted after second revision 21 November 2011

Publication Date:
28 December 2011 (online)

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Abstract

Glucocorticoid (GC) excess promotes adipose tissue accumulation, and 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) plays an important role in the local amplification of GC. Therefore, in this study, we investigated the effects of carbenoxolone (CBX), an 11β-HSD1 inhibitor, on morphological changes in visceral fat, and the expression of genes involved in adipogenesis and lipid metabolism in high-fat (HF) diet-fed mice. Mice were fed a HF diet from 5 weeks of age. At 10 weeks of age, the mice received an intraperitoneal injection of CBX or vehicle every day for 2 weeks. CBX decreased body weight and visceral fat mass, and improved insulin sensitivity in HF-fed mice. This was accompanied by reduced adipocyte size and a decrease in large-sized adipocytes in visceral fat. The expression of adipogenesis (PPARγ and C/EBPα), glucose transport (GLUT4) and lipid metabolism (LPL, ATGL, and HSL)-related genes were suppressed in CBX mice. CBX treatment induced beneficial morphological changes in visceral fat and decreased the expression of adipogenesis, glucose transport and lipid metabolism-related genes. These findings reveal a potential mechanism underling the effects of CBX on reduced fat accumulation and improved insulin sensitivity.

Key words

visceral fat - 11β-hydroxysteroid dehydrogenase type 1 - glucocorticoid - morphology - adipogenesis
 

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