Tumor necrosis factor-alpha stimulates cell proliferation in adipose tissue-derived stromal-vascular cell culture: Promotion of adipose tissue expansion by paracrine growth factors

Citation
Km. Kras et al., Tumor necrosis factor-alpha stimulates cell proliferation in adipose tissue-derived stromal-vascular cell culture: Promotion of adipose tissue expansion by paracrine growth factors, OBES RES, 8(2), 2000, pp. 186-193
Citations number
47
Categorie Soggetti
Endocrinology, Nutrition & Metabolism
Journal title
OBESITY RESEARCH
ISSN journal
10717323 → ACNP
Volume
8
Issue
2
Year of publication
2000
Pages
186 - 193
Database
ISI
SICI code
1071-7323(200003)8:2<186:TNFSCP>2.0.ZU;2-E
Abstract
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.