PMID- 9392477
OWN - NLM
STAT- MEDLINE
DCOM- 19971223
LR  - 20220321
IS  - 0012-1797 (Print)
IS  - 0012-1797 (Linking)
VI  - 46
IP  - 12
DP  - 1997 Dec
TI  - Tumor necrosis factor-alpha induces apoptosis of human adipose cells.
PG  - 1939-44
AB  - Tumor necrosis factor-alpha (TNF-alpha) production by adipocytes is elevated in 
      obesity, as shown by increased adipose tissue TNF-alpha mRNA and protein levels 
      and by increased circulating concentrations of the cytokine. Furthermore, 
      TNF-alpha has distinct effects on adipose tissue including induction of insulin 
      resistance, induction of leptin production, stimulation of lipolysis, suppression 
      of lipogenesis, induction of adipocyte dedifferentiation, and impairment of 
      preadipocyte differentiation in vitro. Taken together, these effects all tend to 
      decrease adipocyte volume and number and suggest a role for TNF-alpha in limiting 
      increase in fat mass. The aim of the present study was to determine if TNF-alpha 
      could induce apoptosis in human adipose cells, hence delineating another 
      mechanism by which the cytokine could act to limit the development of, or extent 
      of, obesity. Cultured human preadipocytes and mature adipocytes in explant 
      cultures were exposed in vitro to human TNF-alpha at varying concentrations for 
      up to 24 h. Apoptosis was assessed using morphological (histology, nuclear 
      morphology following acridine orange staining, electron microscopy) and 
      biochemical (demonstration of internucleosomal DNA cleavage by gel 
      electrophoresis and of annexin V staining using immunocytochemistry) criteria. In 
      control cultures, apoptotic indexes were between 0 and 2.3% in all experiments. 
      In the experimental systems, TNF-alpha induced apoptosis in both preadipocytes 
      and adipocytes, with indexes between 5 and 25%. Therefore, TNF-alpha induces 
      apoptosis of human preadipocytes and adipocytes in vitro. In view of the major 
      metabolic role of TNF-alpha in human adipose tissue, and the knowledge that 
      adipose tissue is dynamic (with cell acquisition via preadipocyte 
      replication/differentiation and cell loss via apoptosis), these findings describe 
      a further mechanism whereby adipose tissue mass may be modified by TNF-alpha.
FAU - Prins, J B
AU  - Prins JB
AD  - Department of Medicine, University of Cambridge, Addenbrooke's Hospital, England, 
      U.K. jprins@hgmp.mrc.ac.uk
FAU - Niesler, C U
AU  - Niesler CU
FAU - Winterford, C M
AU  - Winterford CM
FAU - Bright, N A
AU  - Bright NA
FAU - Siddle, K
AU  - Siddle K
FAU - O'Rahilly, S
AU  - O'Rahilly S
FAU - Walker, N I
AU  - Walker NI
FAU - Cameron, D P
AU  - Cameron DP
LA  - eng
GR  - Wellcome Trust/United Kingdom
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Diabetes
JT  - Diabetes
JID - 0372763
RN  - 0 (Annexin A5)
RN  - 0 (Coloring Agents)
RN  - 0 (Culture Media, Serum-Free)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - F30N4O6XVV (Acridine Orange)
SB  - IM
MH  - Acridine Orange
MH  - Adipocytes/*physiology/ultrastructure
MH  - Annexin A5/analysis
MH  - *Apoptosis
MH  - Cells, Cultured
MH  - Coloring Agents
MH  - Culture Media, Serum-Free
MH  - Humans
MH  - Microscopy, Electron
MH  - Microscopy, Fluorescence
MH  - Stem Cells/chemistry/physiology
MH  - Tumor Necrosis Factor-alpha/*pharmacology
EDAT- 1997/12/10 00:00
MHDA- 1997/12/10 00:01
CRDT- 1997/12/10 00:00
PHST- 1997/12/10 00:00 [pubmed]
PHST- 1997/12/10 00:01 [medline]
PHST- 1997/12/10 00:00 [entrez]
AID - 10.2337/diab.46.12.1939 [doi]
PST - ppublish
SO  - Diabetes. 1997 Dec;46(12):1939-44. doi: 10.2337/diab.46.12.1939.