A potential role for 5-androstene-3β,7β,17β-triol in obesity and metabolic syndrome.
Metabolic syndrome is marked by perturbed glucocorticoid (GC) signaling, systemic inflammation, and altered immune status. Dehydroepiandrosterone (DHEA), a major circulating adrenal steroid and dietary supplement, demonstrates antiobesity, anti-inflammatory, GC-opposing and immune-modulating activity when administered to rodents. However, plasma DHEA levels failed to correlate with metabolic syndrome and oral replacement therapy provided only mild benefits to patients. Androstene-3β,7β,17β-triol (β-AET) an anti-inflammatory metabolite of DHEA, also exhibits GC-opposing and immune-modulating activity when administered to rodents. We hypothesized a role for β-AET in obesity. We now report that plasma levels of β-AET positively correlate with BMI in healthy men and women. Together with previous studies, the observations reported here may suggest a compensatory role for β-AET in preventing the development of metabolic syndrome. The β-AET structural core may provide the basis for novel pharmaceuticals to treat this disease.
Auci
Dominick L
DL
Harbor Biosciences, San Diego, California, USA. dauci@harborbiosciences.com
Ahlem
Clarence N
CN
Kennedy
Michael R
MR
Page
Theodore M
TM
Reading
Christopher L
CL
Frincke
James M
JM
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000737:Androstenols / Q000097:blood*; D000893:Anti-Inflammatory Agents / Q000097:blood*; D019440:Anti-Obesity Agents / Q000097:blood*; D015992:Body Mass Index; D003687:Dehydroepiandrosterone / Q000097:blood / Q000627:therapeutic use; D005260:Female; D005938:Glucocorticoids / Q000037:antagonists & inhibitors; D006801:Humans; D016014:Linear Models; D008297:Male; D024821:Metabolic Syndrome / Q000378:metabolism*; D008875:Middle Aged; D009765:Obesity / Q000378:metabolism*; D013256:Steroids / Q000494:pharmacology; D055815:Young Adult
C108492:5-androstene-3,7,17-triol; D000737:Androstenols; D000893:Anti-Inflammatory Agents; D019440:Anti-Obesity Agents; D005938:Glucocorticoids; D013256:Steroids; D003687:Dehydroepiandrosterone