Differential impact of low birth weight on PPAR and leptin expression in perirenal fat in male and female lambs

Abstract

Scientific Abstract 93. Objective: Epidemiological studies have shown that a low birth weight coupled with a rapid postnatal growth rate is associated with an increased adiposity in adult life. We have investigated the impact of low birth weight and gender on the expression of genes that regulate the differentiation (PPARy, RXRa), insulin sensitivity (adiponectin) and lipid metabolism (leptin, LPL, G3PDH) of perirenal adipocytes in lambs at 21d of life. Methods: Lambs were separated into low birth weight (LBW, <4.4 kg, n=9) and average birth weight (ABW, >4.5kg, n=15) groups. An Insulin RIA and competitive ELISA for leptin were used for plasma analyses. The relative quantity of PPARy, RXRa, leptin, adiponectin, LPL, and G3PDH mRNA in the perirenal fat depot was determined by qRT-PCR, and the mean size of adipocytes was determined using standard image analysis. Results: There was no difference between LBW and ABW lambs in the relative perirenal adipose tissue (PAT) mass at 21d. Plasma insulin concentrations during the first 24h after birth were strongly correlated with size of perirenal adipocytes at 21d (r²=0.57, P<0.0002). PPARg (P<0.05) and leptin (P<0.001) expression in PAT was lower in LBW compared with ABW male lambs. There were also significant relationships between both PPARy and leptin expression in PAT and birth weight in males. In contrast, birth weight did not influence PPARy and leptin expression in female lambs. Female lambs had lower plasma insulin concentrations and higher relative PAT mass (P<0.05) than males, and in females PPARy expression was directly related to mean plasma insulin (r²=0.41, P<0.05) and the size of perirenal adipocytes (r²=0.64, P<0.01). In females, leptin expression in PAT was also related to the size of perirenal adipocytes (r²=0.50, P<0.05). Plasma leptin was not different between LBW and ABW lambs, or between male and female lambs, and was not related to any measure of fat mass at 21d. There was no effect of birth weight or gender on RXRa, adiponectin, LPL or G3PDH expression in perirenal fat. Conclusions: There are differences in the effects of birth weight on adipose gene expression in male and female lambs. We postulate that the reduced expression of PPARy and leptin in perirenal fat of LBW male lambs may be related to an impaired insulin sensitivity, when compared with female lambs. The differential effect of birth weight on adipocyte gene expression in male and female lambs may be important in gender specific programming of an increase in visceral fat mass in adult life.