Obesity is accompanied by disturbances in peripheral glucocorticoid metabolism and changes in FA recycling.
Artikel i vetenskaplig tidskrift, 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

Författare

Kotryna Simonyte

Eva Rask

Ingmar Näslund

Jan-Erik Angelhed

Göteborgs universitet

Lars Lönn

Göteborgs universitet

Tommy Olsson

Cecilia Mattsson

Obesity

1930-7381 (ISSN)

Vol. 17 11 1982-7

Ämneskategorier

MEDICIN OCH HÄLSOVETENSKAP

Radiologi och bildbehandling

DOI

10.1038/oby.2009.99

PubMed

19360009