Tumor necrosis factor-alpha stimulates cell proliferation in adipose tissue-derived stromal-vascular cell culture: promotion of adipose tissue expansion by paracrine growth factors.
OBJECTIVE
Elevated levels of tumor necrosis factor-alpha (TNF-alpha) protein and mRNA have been reported in adipose tissue from obese humans and rodents. However, TNF-alpha has catabolic and antiadipogenic effects on adipocytes. Addressing this paradox, we tested the hypothesis that paracrine levels of TNF-alpha, alone or together with insulin-like growth factor-I (IGF-I), support preadipocyte development.


METHODS
Cultured stromal-vascular cells from rat inguinal fat depots were exposed to serum-free media containing insulin and 0.2 nM TNF-alpha, 2.0 nM TNF-alpha, or 0.2 nM TNF-alpha + 1.0 nM IGF-I at different times during 7 days of culture.


RESULTS
TNF-alpha inhibited adipocyte differentiation as indicated by a reduction in both immunocytochemical reactivity for the preadipocyte-specific antigen (AD3; early differentiation marker) and glycerol-3-phosphate dehydrogenase activity (late differentiation marker). Early exposure (Days 1 through 3 of culture) to 0.2 nM TNF-alpha did not have a long term effect on inhibiting differentiation. Continuous exposure to 0.2 nM TNF-alpha from Days 1 through 7 of culture resulted in a 75% increase in cell number from control. There was a synergistic effect of 0.2 nM TNF-alpha + 1 nM IGF-I on increasing cell number by Day 7 of culture to levels greater than those observed with either treatment applied alone.


CONCLUSIONS
These data suggest that paracrine levels (0.2 nM) of TNF-alpha alone or in combination with IGF-I may support adipose tissue development by increasing the total number of stromal-vascular and/or uncommitted cells within the tissue. These cells may then be recruited to become preadipocytes or may alternatively serve as infrastructure to support adipose tissue growth.
Kras
K M
KM
Department of Foods and Nutrition, University of Georgia, Athens 30602, USA.
Hausman
D B
DB
Martin
R J
RJ
D017667:Adipocytes / Q000166:cytology*; D000273:Adipose Tissue / Q000098:blood supply; D000818:Animals; D001808:Blood Vessels / Q000166:cytology*; D002454:Cell Differentiation; D002455:Cell Division; D002478:Cells, Cultured; D016895:Culture Media, Serum-Free; D006133:Growth Substances / Q000494:pharmacology*; D007328:Insulin / Q000494:pharmacology; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D017154:Stromal Cells / Q000166:cytology*; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*
D016895:Culture Media, Serum-Free; D006133:Growth Substances; D007328:Insulin; D014409:Tumor Necrosis Factor-alpha; D007334:Insulin-Like Growth Factor I