Dehydroepiandrosterone (DHEA) treatment in vitro inhibits adipogenesis in human omental but not subcutaneous adipose tissue.
Dehydroepiandrosterone (DHEA), a precursor sex steroid, circulates in sulphated form (DHEAS). Serum DHEAS concentrations are inversely correlated with metabolic syndrome components and in vivo/in vitro studies suggest a role in modulating adipose mass. To investigate further, we assessed the in vitro biological effect of DHEA in white (3T3-L1) and brown (PAZ6) preadipocyte cell lines and human primary preadipocytes. DHEA (from 10(-8)M) caused concentration-dependent proliferation inhibition of 3T3-L1 and PAZ6 preadipocytes. Cell cycle analysis demonstrated unaltered apoptosis but indicated blockade at G1/S or G2/M in 3T3-L1 and PAZ6, respectively. Preadipocyte cell-line adipogenesis was not affected. In human primary subcutaneous and omental preadipocytes, DHEA significantly inhibited proliferation from 10(-8)M. DHEA 10(-7)M had opposing effects on adipogenesis in the two fat depots. Subcutaneous preadipocyte differentiation was unaffected or increased whereas omental preadipocytes showed significantly reduced adipogenesis. We conclude that DHEA exerts fat depot-specific differences which modulate body composition by limiting omental fat production.
Rice
S P L
SP
Centre for Endocrine and Diabetes Sciences, School of Medicine, Cardiff University, Heath Park, Cardiff CF14 4XN, UK.
Zhang
L
L
Grennan-Jones
F
F
Agarwal
N
N
Lewis
M D
MD
Rees
D A
DA
Ludgate
M
M
D017667:Adipocytes / Q000166:cytology / Q000187:drug effects / Q000201:enzymology; D050156:Adipogenesis / Q000187:drug effects* / Q000235:genetics; D052242:Adiponectin / Q000096:biosynthesis; D000368:Aged; D002453:Cell Cycle / Q000187:drug effects; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects; D003687:Dehydroepiandrosterone / Q000494:pharmacology*; D005260:Female; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D006801:Humans; D008071:Lipoprotein Lipase / Q000235:genetics / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009852:Omentum / Q000166:cytology* / Q000187:drug effects* / Q000201:enzymology; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D050151:Subcutaneous Fat / Q000166:cytology* / Q000187:drug effects* / Q000201:enzymology
D052242:Adiponectin; D012333:RNA, Messenger; D003687:Dehydroepiandrosterone; D008071:Lipoprotein Lipase