Obesity is accompanied by disturbances in peripheral glucocorticoid metabolism and changes in FA recycling.
Journal article, 2009
The glucocorticoid activating enzyme 11beta-hydroxysteroid dehydrogenase type 1 (11betaHSD1) is of major interest in obesity-related morbidity. Alterations in tissue-specific cortisol levels may influence lipogenetic and gluco/glyceroneogenetic pathways in fat and liver. We analyzed the expression and activity of 11betaHSD1 as well as the expression of phosphoenolpyruvate carboxykinase (PEPCK), sterol regulatory element binding protein (SREBP), and fatty acid synthase (FAS) in adipose and liver and investigated putative associations between 11betaHSD1 and energy metabolism genes. A total of 33 obese women (mean BMI 44.6) undergoing gastric bypass surgery were enrolled. Subcutaneous adipose tissue (SAT), omental fat (omental adipose tissue (OmAT)), and liver biopsies were collected during the surgery. 11betaHSD1 gene expression was higher in SAT vs. OmAT (P = 0.013), whereas the activity was higher in OmAT (P = 0.009). The SAT 11betaHSD1 correlated with waist circumference (P = 0.045) and was an independent predictor for the OmAT area in a linear regression model. Energy metabolism genes had AT depot-specific expression; higher leptin and SREBP in SAT than OmAT, but higher PEPCK in OmAT than SAT. The expression of 11betaHSD1 correlated with PEPCK in both AT depots (P = 0.05 for SAT and P = 0.0001 for OmAT). Hepatic 11betaHSD1 activity correlated negatively with abdominal adipose area (P = 0.002) and expression positively with PEPCK (P = 0.003). In human obesity, glucocorticoid regeneration in the SAT is associated with central fat accumulation indicating that the importance of this specific fat depot is underestimated. Central fat accumulation is negatively associated with hepatic 11betaHSD1 activity. A disturbance in peripheral glucocorticoid metabolism is associated with changes in genes involved in fatty acid (FA) recycling in adipose tissue (AT).
Messenger
Subcutaneous Fat
genetics
Middle Aged
metabolism
Abdominal
Obesity
Female
enzymology
RNA
Reverse Transcriptase Polymerase Chain Reaction
metabolism
Sterol Regulatory Element Binding Proteins
Adult
Glucocorticoids
metabolism
Waist Circumference
metabolism
enzymology
metabolism
metabolism
metabolism
Leptin
Fatty Acids
genetics
Adiposity
genetics
metabolism
Liver
Intra-Abdominal Fat
11-beta-Hydroxysteroid Dehydrogenase Type 1
metabolism
enzymology
genetics
Phosphoenolpyruvate Carboxykinase (ATP)
Humans
genetics
Fatty Acid Synthetase Complex
Author
Kotryna Simonyte
Eva Rask
Ingmar Näslund
Jan-Erik Angelhed
University of Gothenburg
Lars Lönn
University of Gothenburg
Tommy Olsson
Cecilia Mattsson
Obesity
1930-7381 (ISSN)
Vol. 17 11 1982-7Subject Categories
MEDICAL AND HEALTH SCIENCES
Radiology, Nuclear Medicine and Medical Imaging
DOI
10.1038/oby.2009.99
PubMed
19360009