Tumour necrosis factor-alpha exerts dual effects on human adipose leptin synthesis and release

Mol Cell Endocrinol. 2000 Jan 25;159(1-2):79-88. doi: 10.1016/s0303-7207(99)00194-x.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adipocytes / cytology
  • Adipocytes / drug effects*
  • Adipocytes / physiology*
  • Adult
  • Aged
  • Cell Differentiation / drug effects
  • Female
  • Glycerolphosphate Dehydrogenase / genetics
  • Glycerolphosphate Dehydrogenase / metabolism
  • Humans
  • In Vitro Techniques
  • Leptin / biosynthesis*
  • Leptin / genetics
  • Leptin / metabolism*
  • Male
  • Middle Aged
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Tumor Necrosis Factor-alpha / pharmacology*


  • Leptin
  • RNA, Messenger
  • Tumor Necrosis Factor-alpha
  • Glycerolphosphate Dehydrogenase