Moderate global reduction in maternal nutrition has differential stage of gestation specific effects on {beta}1- and {beta}2-adrenergic receptors in the fetal baboon liver

Abstract

Hepatic β-adrenergic receptors (β-ARs) play a pivotal role in mobilization of reserves via gluconeogenesis and glycogenolysis to supply the animal with its energy needs during decreased nutrient availability. Using a unique nutrient-deprived baboon model, we have demonstrated for the first time that immunoreactive hepatic β(1)- and β(2)-AR subtypes are regionally distributed and localized on cells around the central lobular vein in 0.5 and 0.9 gestation (G) fetuses of ad libitum fed control (CTR) and maternal nutrient restricted (MNR) mothers. Furthermore, MNR decreased fetal liver immunoreactive β(1)-AR and increased immunoreactive β(2)-AR at 0.5G. However, at 0.9G, immunohistochemistry and Western blot analysis revealed a decrease in β(1)-AR and no change in β(2)-AR levels. Thus, MNR in a nonhuman primate species has effects on hepatic β(1)- and β(2)-ARs that are receptor- and gestation stage-specific and may represent compensatory systems whose effects would increase glucose availability in the presence of nutrient deprivation.

Figure 1.

Immunoreactive β₁-adrenergic receptors (AR; A-D) and β₂-AR (E-H) in fetal baboon liver at 0.5 and 0.9 gestation (G). β₁- and β₂-AR immunoreactivity in liver of fetuses from mothers fed ad libitum (A, C and E, G) or nutrient-restricted (B, D and F, H) from 0.16G to 0.5G (A, B and E, F) or 0.9G (C, D and G, H). Central vein (CV). Panels A, B (50 µm); Panels C, D (100 µm); Panels E-H (50 µm).

Figure 2.

β₁-adrenergic receptors (AR) and β₂-AR immunoreactivity in fetal baboon liver. β₁-AR (panels A and B) and β₂-AR (panels C and D) immunoreactivity, expressed as density and fraction, at 0.5G and 0.9 gestation (G) in fetal baboon liver from mothers that were fed ad libitum (control [CTR], ▪) or 70% CTR diet (maternal nutrient restricted [MNR], □) from 0.16G to 0.5G (N = 8 CTR, 6 MNR) or 0.9G (N = 7 CTR, 6 MNR). Data expressed as mean ± SEM; *, P < .05 versus CTR.

Figure 3.

β₁-adrenergic receptors (AR) and β₂-AR protein and messenger RNA (mRNA) levels in fetal baboon liver at 0.9 gestation (G). β₁-AR (panel A) and β₂-AR (panel B) protein levels in fetal baboon liver at 0.9G from mothers fed ad libitum (control [CTR], ▪, N = 7), or 70% CTR diet (maternal nutrient restricted [MNR], □, N = 6) as measured by Western blotting. Inset shows representative immunoblots from 3 CTR and 3 MNR fetuses and protein levels of β-actin that were used as loading controls. Panel C: β₁- and β₂-AR mRNA levels as determined by quantitative reverse transcription−polymerase chain reaction (qRT-PCR) in liver homogenates from 0.9G fetuses of mothers on CTR or MNR diet. Data expressed as mean ± SEM; *, P < .05 compared to CTR.