Regional variation in adipogenesis and IGF regulatory proteins in the fetal baboon

Abstract

Intrauterine growth rate is associated with body distribution in adulthood suggesting differential response of fetal fat depots to nutritional modifications. We hypothesize that there is regional differences in fetal adipogenesis, in part, due to depot-specific regulation of the availability of insulin growth factors. In near-term baboon fetuses (n=3-5), the subcutaneous abdominal vs. omental preadipocytes had (1) more extensive lipid accumulation as assessed by BODIPY (lipid staining) to DAPI (nuclei) absorbance ratios (mean+/-SEM; 0.51+/-0.21, 0.35+/-0.09, p<0.05), (2) lower (p<0.05) secretion of IGF-binding protein 4 (9.6+/-1.2 vs. 17.4+/-2.8 ng/ml) and its protease pregnancy associated plasma protein A (24.6+/-1.9 vs. 39.1+/-6.3 microIU/ml), (3) lower protein expression of IGF2 "clearance" receptor in cell lysate (0.28+/-0.03 vs. 0.53+/-0.02 OD U/mm(2), p<0.05); all variables were intermediate in femoral preadipocytes. The regional variation of the adipogenesis and the IGF regulatory pathway set the stage for differential responsiveness of fat depots to external signals.

Figures

Fig. 1

125I-IGFBP-4 protease activity of PAPP-A. Conditioned media from OM, SQ ABD, and FEM SV cultures from 2 baboon fetuses were incubated with 125I-IGFBP-4 and 5 nM IGF-II at 37 °C for 24 h. The radio-labeled fragment (18 kDa) resulting from the proteolysis of 125I-IGFBP-4 by PAPP-A and the remaining intact 125I-IGFBP-4 were separated on SDS gel and visualized by auto-radiography. Conditioned media from OM SV cultures exhibited IGF-II independent greatest loss of intact 125IGFBP-4s coupled with greatest generation of 18-kDa fragments indicating highest PAPP-A proteolytic activities.

Fig. 2

Immunoblots for IGF receptors in adipose-derived SV cultures by fat depots (n = 4). (A) IGF1R protein expression was similar among depots. Mean ± SEM; SQ ABD, 0.69 ± 0.24; FEM, 1.00 ± 0.24; OM, 0.65 ± 0.24 U/mm2 (B) IGF2R protein expression was higher in OM compared to both SQ ABD and FEM fat depots. Mean ± SEM: SQ ABD, 0.28 ± 0.03a; FEM, 0.34 ± 0.04ab; OM, 0.53 ± 0.02b U/mm2. Different letters in the superscripts indicate a difference among depots, p < 0.05.