Tumor Necrosis Factor-α Stimulates Cell Proliferation in Adipose Tissue-Derived Stromal-Vascular Cell Culture: Promotion of Adipose Tissue Expansion by Paracrine Growth Factors


Department of Foods and Nutrition, 269 Dawson Hall, University of Georgia, Athens, GA 30602. E-mail: dhausman@arches.uga.edu


Objective: Elevated levels of tumor necrosis factor-α (TNF-α) protein and mRNA have been reported in adipose tissue from obese humans and rodents. However, TNF-α has catabolic and antiadipogenic effects on adipocytes. Addressing this paradox, we tested the hypothesis that paracrine levels of TNF-α, alone or together with insulin-like growth factor-I (IGF-I), support preadipocyte development.

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

Results: TNF-α 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-α did not have a long term effect on inhibiting differentiation. Continuous exposure to 0.2 nM TNF-α 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-α + 1 nM IGF-I on increasing cell number by Day 7 of culture to levels greater than those observed with either treatment applied alone.

Discussion: These data suggest that paracrine levels (0.2 nM) of TNF-α 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.