Carbenoxolone alters the morphology of adipose tissues and downregulates genes involved in adipogenesis, glucose transport and lipid metabolism in high-fat diet-fed mice.
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.
Department of Pediatrics, Hamamatsu University School of Medicine, Hamamatsu, Shizuoka, Japan. sanosin2u@yahoo.co.jp
S
S
Sano
Y
Y
Nakagawa
R
R
Yamaguchi
Y
Y
Fujisawa
E
E
Satake
E
E
Nagata
T
T
Nakanishi
Y-J
YJ
Liu
T
T
Ohzeki
D017667:Adipocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D050156:Adipogenesis / Q000187:drug effects / Q000235:genetics*; D000273:Adipose Tissue / Q000033:anatomy & histology* / Q000187:drug effects / Q000378:metabolism*; D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects; D002229:Carbenoxolone / Q000494:pharmacology*; D059305:Diet, High-Fat; D015536:Down-Regulation / Q000187:drug effects* / Q000235:genetics; D005247:Feeding Behavior / Q000187:drug effects; D005947:Glucose / Q000378:metabolism*; D005951:Glucose Tolerance Test; D007328:Insulin / Q000378:metabolism; D050152:Intra-Abdominal Fat / Q000187:drug effects / Q000378:metabolism; D050356:Lipid Metabolism / Q000187:drug effects / Q000235:genetics*; D050155:Lipogenesis / Q000187:drug effects / Q000235:genetics; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009929:Organ Size / Q000187:drug effects; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism
D007328:Insulin; D012333:RNA, Messenger; D005947:Glucose; D002229:Carbenoxolone