Hippocampal 11beta-hydroxysteroid dehydrogenase type 1 messenger ribonucleic acid expression has a diurnal variability that is lost in the obese Zucker rat.
Circulating levels of glucocorticoids show a circadian rhythm. Obesity is associated with a flattening of the diurnal rhythm; plasma cortisol levels are slightly increased during the trough, although they are normal or low in the morning. Studies in humans and in leptin-resistant Zucker rats suggest that tissue-specific alterations in glucocorticoid exposure might play a key role for development of obesity and obesity-associated dysregulation of the hypothalamic-pituitary-adrenal axis. We hypothesized that there is a circadian rhythm in prereceptor metabolism of glucocorticoids exerted by 11beta-hydroxysteroid dehydrogenase type 1 (11beta-HSD1) in brain and/or peripheral tissues (liver, fat, and muscle) that might be abrogated in obesity. The present study demonstrates a circadian rhythm in 11beta-HSD1 mRNA expression (35-45% increase at morning vs. evening, P < 0.05) in dentate gyrus granular layer and CA1 subregions of the hippocampus in lean Zucker rats that was lost in the obese rats. Sprague Dawley rats also revealed a diurnal rhythm in hippocampal 11beta-HSD1 mRNA expression. There was no circadian variation in 11beta-HSD enzyme activity in peripheral tissues, although obese Zucker rats had a decreased enzyme activity in liver and epididymal fat (by approximately 40%, P < 0.05) compared with lean rats. In Sprague Dawley rats, 11beta-HSD activity in adipose tissue was higher in retroperitoneal and epididymal vs. sc fat (P < 0.001). In summary, obese Zucker rats lack a circadian rhythm of 11beta-HSD1 gene expression in the hippocampus, which may contribute to increased activity of the hypothalamic-pituitary-adrenal axis and altered diurnal variation of circulating corticosterone levels.
Burén
Jonas
J
Department of Public Health and Clinical Medicine, Umeå University Hospital, SE-901 85 Umeå, Sweden. jonas.buren@medicin.umu.se
Bergström
Sven-Anders
SA
Loh
Edmund
E
Söderström
Ingegerd
I
Olsson
Tommy
T
Mattsson
Cecilia
C
D043205:11-beta-Hydroxysteroid Dehydrogenase Type 1 / Q000235:genetics* / Q000378:metabolism; D000818:Animals; D002540:Cerebral Cortex / Q000201:enzymology / Q000378:metabolism; D002940:Circadian Rhythm; D003345:Corticosterone / Q000097:blood; D015971:Gene Expression Regulation, Enzymologic; D006624:Hippocampus / Q000201:enzymology / Q000378:metabolism*; D008297:Male; D009765:Obesity / Q000097:blood / Q000201:enzymology / Q000235:genetics*; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D011924:Rats, Zucker
D012333:RNA, Messenger; D043205:11-beta-Hydroxysteroid Dehydrogenase Type 1; D003345:Corticosterone