Circulating Leptin Concentrations Are Positively Related to Leptin Messenger RNA Expression in the Adipose Tissue of Fetal Sheep in the Pregnant Ewe Fed at or Below Maintenance Energy Requirements During Late Gestation1

Abstract

We have investigated the effects of maternal undernutrition during late gestation on maternal and fetal plasma concentrations of leptin and on leptin gene expression in fetal perirenal adipose tissue. Pregnant ewes were randomly assigned at 115 days of gestation (term = 147 +/- 3 days [mean +/- SEM]) to either a control group (n = 13) or an undernourished group (n = 16) that received approximately 50% of the control diet until 144-147 days of gestation. Maternal plasma glucose, but not leptin, concentrations were lower in the undernourished ewes. A significant correlation was found, however, between mean maternal plasma leptin (y) and glucose (x) concentrations (y = 2.9x - 2.4; r = 0.51, P < 0.02) when the control and undernourished groups were combined. Fetal plasma glucose and insulin, but not fetal leptin, concentrations were lower in the undernourished ewes, and no correlation was found between mean fetal leptin concentrations and either mean fetal glucose or insulin concentrations. A positive relationship, however, was found between mean fetal (y) and maternal (x) plasma leptin concentrations (y = 0.18x + 0.45; r = 0.66, P < 0.003). No significant difference was found in the relative abundance of leptin mRNA in fetal perirenal fat between the undernourished (0.60 +/- 0.09, n = 10) and control (0.70 +/- 0.08, n = 10) groups. Fetal plasma concentrations of leptin (y) and leptin mRNA levels (x) in perirenal adipose tissue were significantly correlated (y = 1.5x +/- 0.3; r = 0.69, P < 0.05). In summary, the capacity of leptin to act as a signal of moderate maternal undernutrition may be limited before birth in the sheep.

Effect of protein or energy restriction during late gestation on hormonal and metabolic status in pregnant goats and postnatal male offspring

“…The decreased plasma GLU concentration of pregnant goats induced by 40% protein or energy restriction during late gestation was consistent with the previous finding using sheep as the animal model (Yuen et al, 2002). GLU is the major energy source in pregnant mothers, not only for maintaining survival of their own tissues and organs, but also for fetal growth.…”

Long Term Consequences of Low Birthweight on Postnatal Growth, Adiposity and Brain Weight at Maturity in Sheep

“…In one study, fetal plasma leptin was positively correlated with plasma cortisol, but inversely correlated with PaO2 [31]. Fetal body weight was shown to be inversely related to plasma leptin concentrations in one study [32] but in another [33] body weight was positively correlated with leptin mRNA, which strongly correlates with plasma leptin [34]. We have not [12] and in 70-75 year old men and women [10].…”

Endocrine and nutritional regulation of fetal adipose tissue development

“…These include voltage-dependent anion channel (VDAC), located on the outer mitochondrial membrane, which has a role in regulating the supply of mitochondrial ATP and ADP (Gottlieb 2000). VDAC abundance in fetal adipose tissue is not nearly as responsive to endocrine stimulation as UCP1 (Budge et al 2002, Yuen et al 2002, Mostyn et al 2003a.…”

“…Reduced maternal nutrition in late gestation results in smaller fat depots with less UCP1 (Symonds et al 1998, Budge et al 2001, in conjunction with lower fetal plasma glucose and insulin, but has no effect of fetal leptin or prolactin receptor mRNA abundance (Symonds et al 1998, Yuen et al 2002. After birth, however, there appears to be a compensatory increase in VDAC abundance in nutrient-restricted offspring (Budge et al 2003) that is maintained up to at least 1 month of age (Mostyn et al 2003b).…”