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) o n leptin production by human preadipocytes, differentiated preadipocytes, a nd mature adipocytes have been examined by competitive RT-PCR of leptin mRN A 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 d ifferentiated preadipocytes and mature adipocytes, TNF-alpha treatment resu lted in time-dependent decreases in mRNA for leptin and glycerol-3-phosphat e dehydrogenase (G3PD). In contrast, TNF-alpha (4-8-h treatment) resulted i n a 4-fold increase in leptin release. This effect was lost at 24 h and lep tin accumulation in culture medium was decreased 24-48 h after TNF-alpha ad dition. We conclude that TNF-alpha stimulates the release of preformed lept in 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 differen tiation and induction of adipocyte dedifferentiation. (C) 2000 Elsevier Sci ence Ireland Ltd. All rights reserved.