Objective: Elevated levels of tumor necrosis factor-alpha (TNF-alpha) prote
in and mRNA have been reported in adipose tissue from obese humans and rode
nts. However, TNF-alpha has catabolic and antiadipogenic effects on adipocy
tes. Addressing this paradox, we tested the hypothesis that paracrine level
s of TNF-alpha, alone or together with insulin-like growth factor-I (IGF-I)
, support preadipocyte development.
Research Methods and Procedures: Cultured stromal-vascular cells from rat i
nguinal 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 d
ifferent times during 7 days of culture.
Results: TNF-alpha inhibited adipocyte differentiation as indicated by a re
duction in both immunocytochemical reactivity for the preadipocyte-specific
antigen (AD3; early differentiation marker) and glycerol-3-phosphate dehyd
rogenase activity (late differentiation marker). Early exposure (Days 1 thr
ough 3 of culture) to 0.2 nM TNF-alpha did not have a long term effect on i
nhibiting differentiation. Continuous exposure to 0.2 nM TNF-alpha from Day
s 1 through 7 of culture resulted in a 75% increase in cell number from con
trol. There was a synergistic effect of 0.2 nM TNF-alpha + 1 nM IGF-I on in
creasing cell number by Day 7 of culture to levels greater than those obser
ved with either treatment applied alone.
Discussion: These data suggest that paracrine levels (0.2 nM) of TNF-alpha
alone or in combination with IGF-I may support adipose tissue development b
y increasing the total number of stromal-vascular and/or uncommitted cells
within the tissue. These cells may then be recruited to become preadipocyte
s or may alternatively serve as infrastructure to support adipose tissue gr
owth.