Endocrine Abstracts (2003) 5 P95

Subcutaneous and visceral preadipocytes from pre-pubertal children show site-specific differences in insulin action

MJ Grohmann1,2, MA Sabin2, JMP Holly1, JPH Shield2, EC Crowne2 & CEH Stewart1

1Department of Surgery, University of Bristol, Bristol, UK; 2Institute of Child Health, University of Bristol, Bristol, UK.

Childhood obesity is increasing in prevalence and is associated with insulin resistance and Type II diabetes in later life. Site-specific differences in adipose tissue accumulation and associated insulin sensitivity may contribute to these problems.
The aims of our study were: 1. To isolate and characterise, subcutaneous (SC) and visceral (V) preadipocytes using small biopsies from pre-pubertal children (ages:4-8years(n=3)) undergoing elective abdominal surgery, with normal BMI and glucose tolerance. 2. To investigate for site-specific variations in insulin mediated signal transduction.
METHODS: Following ethical approval, SC and V preadipocytes were successfully isolated from adipose tissue (0.2-0.5grams) by collagenase digestion. At confluence cells were differentiated [1] and characterised histologically using Oil Red O. As a measure of insulin sensitivity, preadipocytes were stimulated with 5 nanograms per ml insulin and GSK-3 and MAPK activation assessed over time by Western immuno blotting.
RESULTS: Phosphorylation levels of GSK-3 and MAPK were different between the two adipose compartments. Median (SEM) for GSK-3 phosphorylation (V vs. SC) demonstrated a 5(0.5) vs. 3(0.7) fold increase at 5 minutes and 4(0.3) vs. 7(0.7) fold increase over basal, at 20 minutes respectively. MAPK activation was similar at 5 minutes in both cell types but was sustained at 20 minutes in SC only. Insulin receptor density remained unchanged.
CONCLUSIONS: We have successfully isolated, cultured and differentiated human preadipocytes from children's subcutaneous and visceral fat depots. We have identified a more pronounced and transient mitogenic and metabolic response to insulin in visceral when compared with subcutaneous. The latter showed more prolonged mitogenic and metabolic responses to insulin. These data indicate site-specific differential effects of insulin on children's preadipocyte metabolism. Visceral adiposity may therefore be exacerbated by repetitive insulin stimulation associated with 'grazing' feeding behaviours commonly found in today's children. This needs further study.
1.Hauner H et al JCI (1989):84.1663

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