Undernutrition and stage of gestation influence fetal adipose tissue gene expression

Abstract

Low birthweight is a risk factor for neonatal mortality and adverse metabolic health, both of which are associated with inadequate prenatal adipose tissue development. In the present study, we investigated the impact of maternal undernutrition on the expression of genes that regulate fetal perirenal adipose tissue (PAT) development and function at gestation days 89 and 130 (term=145 days). Singleton fetuses were taken from adolescent ewes that were either fed control (C) intake to maintain adiposity throughout pregnancy or were undernourished (UN) to maintain conception weight but deplete maternal reserves (n=7/group). Fetal weight was independent of maternal intake at day 89, but by day 130, fetuses from UN dams were 17% lighter and had lower PAT mass that contained fewer unilocular adipocytes. Relative PAT expression of IGF1, IGF2, IGF2R and peroxisome proliferator-activated receptor gamma (PPARG) mRNA was lower in UN than in controls, predominantly at day 89. Independent of maternal nutrition, PAT gene expression of PPARG, glycerol-3-phosphate dehydrogenase, hormone sensitive lipase, leptin, uncoupling protein 1 and prolactin receptor increased, whereas IGF1, IGF2, IGF1R and IGF2R decreased between days 89 and 130. Fatty acid synthase and lipoprotein lipase (LPL) mRNAs were not influenced by nutrition or stage of pregnancy. Females had greater LPL and leptin mRNA than males, and LPL, leptin and PPARG mRNAs were decreased in UN at day 89 in females only. PAT gene expression correlations with PAT mass were stronger at day 89 than they were at day 130. These data suggest that the key genes that regulate adipose tissue development and function are active beginning in mid-gestation, at which point they are sensitive to maternal undernutrition: this leads to reduced fetal adiposity by late pregnancy.

Keywords: adipose tissue; fetal; gene expression; sheep; undernutrition.

Figure 1

Haematoxylin and eosin-stained sections of perirenal fat from a representative fetus from a control and an undernourished pregnancy (both females) with unilocular and multilocular fat cells highlighted (a and b), and relationships between perirenal unilocular fat mass and percentage of fat in the carcass (c, r=0.806, P=0.001), and between fetal weight and multilocular fat mass (d, r=0.605, P=0.022) at day 130 of gestation in fetuses from control (□) and undernourished (■) adolescent dams.

Figure 2

Relative leptin (a) and LPL (b) mRNA expression in fetal perirenal fat of female (solid bar) and male (open bar) fetuses from control (C) and undernourished (UN) adolescent dams whose pregnancies were terminated on day 89 or day 130 of gestation. ANOVA was used to determine effects of sex, maternal nutrition, stage of gestation, and all possible interactions. Vertical bars are group mean ± sem and those with different letters differ P<0.05 using Tukey’s post-hoc method. Number of fetuses per group can be derived from Table 3. For leptin, there were effects of gender (P=0.001), stage of gestation (P=0.001), nutrition (P=0.029) and a gender x nutrition interaction (P=0.029). For LPL, there was an effect of gender (P=0.002), and a gender x nutrition x stage of gestation interaction (P=0.008).

Figure 3

Relationships between body weight-specific perirenal adipose tissue (PAT) mass and perirenal fat (a) LPL mRNA (r=0.795, P<0.001) and (b) leptin mRNA (r=0.872, P<0.001) at day 89 of gestation in fetuses from control (□) and undernourished (■) adolescent dams.

Figure 4

Relationships between relative PPARG gene expression and (a) IGF1, (b) G3PDH, (c) LPL and (d) leptin mRNA in fetal perirenal adipose tissue (PAT) at day 89 (●) and 130 (○) of gestation. At day 89 and 130, respectively: r=0.940, P<0.001 and r=0.118, not significant (NS) for (a); r=0.853, P<0.001 and r=0.653, P<0.05 for (b); r=0.910, P<0.001 and r=0.723, P<0.01 for (c); r=0.900, P<0.001 and r=0.242, NS for (d).