Effects of poor maternal nutrition during gestation on gene expression in liver of offspring

Abstract Text: Poor maternal nutrition during gestation can reduce growth and circulating growth factors secreted by the liver, as well as alter lipid metabolism. However, the mechanisms that lead to these alterations are not well understood. We hypothesized that poor maternal nutrition during gestation would alter expression of key genes involved in lipid metabolism and the somatotropic axis in the liver of offspring. Thirty-six multiparous ewes were individually housed and fed 100%, 60%, or 140% of NRC requirements beginning at d 31 ± 1.3 of gestation. Lambs were euthanized within 24 h of birth (1 d; n = 18) or 3 mo of age (n = 15). Lambs from ewes fed 100%, 60%, or 140% will be referred to as CON, RES, and OVER, respectively. At euthanasia, whole livers were harvested, weighed and tissue samples collected. Total RNA was extracted and gene expression determined by real-time reverse transcriptase (RT)-PCR. Data were analyzed using PROC GLM with significance considered at P ≤ 0.05 and a tendency at 0.05 < P ≤ 0.10. As previously reported, BW were 13% greater in OVER vs. CON (P ≤ 0.05). Liver weight was 43% greater in OVER vs. CON (P = 0.08) at 1 d when adjusted for BW, but no difference was observed at 3 mo (P = 0.6). At 1 d, relative to CON, the expression of sterol-regulatory element binding protein-I (SREBP-I), a regulator of hepatic lipogenesis, was reduced 2.6 ± 0.1 and 3.7 ± 0.1-fold in RES and OVER, respectively (P < 0.01). The expression of IGF-I receptor (IGF-IR) was reduced 1.7 ± 0.1 and 2.0 ± 0.2-fold in RES (P = 0.03) and OVER (P = 0.09), respectively at 1 d relative to CON. Expression of IGFBP-4 was reduced 2.6 ± 0.1 and 1.7 ± 0.1-fold in RES (P = 0.01) and OVER (P = 0.07), respectively at 1 d relative to CON. Expression of SREBP-I, IGF-IR, and IGFBP-4 were not altered at 3 mo (P ≥ 0.3). Relative to CON, expression of IGFBP-3 increased 1.7 ± 0.2-fold in OVER (P = 0.04) at 3 mo, but was unaltered at d 1 (P ≥ 0.8). Maternal diet did not affect IGF-I at either time point (P ≥ 0.3). In conclusion, poor maternal nutrition alters genes involved in lipid metabolism and IGF action, which may contribute to altered growth and increased fat deposition in offspring.

Keywords: liver, sheep, somatotropic axis