Tumour necrosis factor-alpha exerts dual effects on human adipose leptin synthesis and release.
The acute and chronic effects of tumour necrosis factor-alpha (TNF-alpha) on leptin production by human preadipocytes, differentiated preadipocytes, and mature adipocytes have been examined by competitive RT-PCR of leptin mRNA and by western blotting. In preadipocytes, secreted leptin was detectable after 5-day incubation in differentiation medium and this increased 4-fold by day 20. TNF-alpha blocked leptin synthesis during differentiation. In differentiated preadipocytes and mature adipocytes, TNF-alpha treatment resulted in time-dependent decreases in mRNA for leptin and glycerol-3-phosphate dehydrogenase (G3PD). In contrast, TNF-alpha (4-8-h treatment) resulted in a 4-fold increase in leptin release. This effect was lost at 24 h and leptin accumulation in culture medium was decreased 24-48 h after TNF-alpha addition. We conclude that TNF-alpha stimulates the release of preformed leptin from human mature adipocytes and existing differentiated preadipocytes, which may contribute to obesity/infection-linked hyperleptinemia, and that TNF-alpha inhibits leptin synthesis via inhibition of preadipocyte differentiation and induction of adipocyte dedifferentiation.
Zhang
H H
HH
Department of Medicine, University of Birmingham, UK.
Kumar
S
S
Barnett
A H
AH
Eggo
M C
MC
D017667:Adipocytes / Q000166:cytology / Q000187:drug effects* / Q000502:physiology*; D000328:Adult; D000368:Aged; D002454:Cell Differentiation / Q000187:drug effects; D005260:Female; D005993:Glycerolphosphate Dehydrogenase / Q000235:genetics / Q000378:metabolism; D006801:Humans; D066298:In Vitro Techniques; D020738:Leptin / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*
D020738:Leptin; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D005993:Glycerolphosphate Dehydrogenase