Author
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HAUSMAN, G - UNIV/FLORIDA |
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Richardson, Richard |
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SIMMEN, FRANK - UAMS |
Submitted to: Growth Development and Aging
Publication Type: Peer Reviewed Journal Publication Acceptance Date: 3/15/2002 Publication Date: 5/1/2002 Citation: HAUSMAN, G.J., RICHARDSON, R.L., SIMMEN, F.A. SECRETION OF INSULIN-LIKE GROWTH FACTOR (IGF)-I AND -II AND IGF BINDING PROTEINS (IGFBPS) IN FETAL STROMAL-VASCULAR (S-V) CELL CULTURES OBTAINED BEFORE AND AFTER ONSET OF ADIPOGENESIS IN VIVO.. GROWTH DEVELOPMENT AND AGING. 2002. v. 66. p. 11-26. Interpretive Summary: The ACNC is interested events that occur early in life, but which have long-term health effects later in life. We studied how the hormone named dexamethasone affects the growth of fat cells taken from fetal pigs. Previous studies had suggested that dexamethasone was important in helping fat cells of the fetus to develop normally during pregnancy. Abnormal growth of these cells during pregnancy may be involved in determining later obesity of the individual. Our goal was to understand if this hormone caused changes in the gene activity for particular types of proteins which are known to control cell activity and which might be affected by nutrition as well. We found that certain proteins which are named IGFBP-3 and IGFBP-4 are made by the fat cells and are affected by the hormone under study. This identifies these two proteins as being important to fetal fat cell development. Future studies will determine the consequences of these effects. Technical Abstract: The present study examined the influence of dexamethasone (DEX) treatment on preadipocyte differentiation and insulin-like growth factor binding protein (IGFBP) secretion in stromal-vascular (S-V) cell cultures established from subcutaneous adipose tissue obtained from nine 75 day and four 50 day pig fetuses. Cultures of S-V cells from four young pigs (5-7 days old) were also studied. Each fetal S-V cell culture represented 1 pool of S-V cells/dam. Cultures were seeded and plated in 10% FBS from day 0-3 and treated with insulin (ITS) + 10 nM DEX from day 3-6 (late DEX treatment). Alternatively, cultures were seeded and plated in 10% FBS + 80 nM DEX from day 0-3 and treated with insulin alone from day 3-6 (early DEX treatment). Conditioned media was collected on day 6 of culture after 3 days of conditioning, and prepared for subsequent 125I-IGF-I ligand blot analysis for IGFBPs and RIA for IGF-I and IGF-II. Early and late DEX increased (P<0.05) preadipocyte (AD-3+) recruitment but only early DEX increased preadipocyte differentiation (lipid + and C/EBP alpha+) by day 6 in S-V cultures from 75 day fetuses. Levels of IGFBP-2, IGFBP-4, IGF-I and IGF-II in media conditioned by 75 day fetal S-V cultures were not influenced by late DEX. However, late DEX reduced levels of 29 kDa IGFBPs and markedly increased (P<0.05) IGFBP-3 levels in 75 day S-V media. Late DEX also markedly increased (P<0.05) IGFBP-3 levels in 50 day S-V media but had little influence on other IGFBPs. Early DEX treatment increased (P<0.05) IGFBP-4 levels in 75 day S-V media but had little to no influence on levels of IGF-I, IGF-II and other IGFBPs. These studies indicate that IGFBP-4 may regulate local metabolism during preadipocyte differentiation, whereas IGFBP-3 may antagonize preadipocyte differentiation by targeting IGF-I away from differentiating cells and towards growing cells. |