Effect of Maternal Nutrition on Brown Adipose Tissue and Its Prolactin Receptor Status in the Fetal Lamb

Abstract

We investigated the influence of maternal nutritional enhancement during the second half of gestation on prolactin receptor (PRLR) abundance in fetal brown adipose tissue (BAT) and liver close to term (i.e. 141-144 d gestation). Ewes were provided with 100% (i.e. control; n = 8) or 150% (i.e. well-fed; n = 7) of their metabolic requirements from 80 to 144 d gestation. Crude plasma membranes were prepared from fetal BAT and hepatic tissue, and individual molecular weight isoforms for the long and short forms of the PRLR were detected by immunoblotting. Mitochondrial preparations were prepared from BAT to measure the amount of the BAT-specific mitochondrial uncoupling protein-1 and its thermogenic activity (i.e. guanosine 5'-diphosphate binding). Fetuses sampled from well-fed ewes were heavier (controls, 3927 +/- 196 g; well-fed, 4783 +/- 219 g; p = 0.01) but possessed less BAT per kilogram body weight (controls, 5.92 +/- 0.43 g/kg; well-fed, 3.85 +/- 0.19 g/kg; p = 0.001), which had a greater uncoupling protein-1 abundance (controls, 56 +/- 5% of reference; well-fed, 78 +/- 9% of reference; p < 0.01) and higher thermogenic activity (controls, 157 +/- 41 pmol guanosine 5'-diphosphate per milligram mitochondrial protein; well-fed, 352 +/- 36 pmol guanosine 5'-diphosphate per milligram mitochondrial protein; p < 0.01) than controls. Multiple isoforms of the long and short forms of the P1LR were detected in all tissues. BAT from well-fed fetuses had a higher abundance of the 15-kD isoform of the long form of the PRLR (controls, 1.6 +/- 0.4 densitometric units; well-fed, 16.3 +/- 2.0 densitometric units; p < 0.001). This isoform was not detected in hepatic tissue. Maternal nutrient intake had no effect on any other isoforms of the PRLR in BAT or liver. In conclusion, increasing the quantity of feed provided in late gestation acts to promote fetal weight and BAT maturation, the combination of which will enhance neonatal viability.

Nutritional programming: prenatal nutritional effects on the regulation of growth and metabolism

“…However, placental glucose transport capacity was not different between the overnourished and the control ewes when expressed on a placental weight-specific basis, indicating that the small size of the placenta per se is the major limitation to placental glucose transfer (Wallace et al, 2002). In contrast, increased nutrient intake during the second half of gestation in adult ewes resulted in greater foetal body mass but less perirenal adipose tissue at day 140 of gestation in the well-fed dams as compared to the control (Budge et al, 2000).…”

“…In addition to alterations of glucocorticoids, insulin and IGF-1, maternal under-or overnutrition during gestation also was reported to result in changes of other maternal hormone levels such as progesterone, oestrogen, prolactin, thyroid hormones, growth hormone and leptin (Wallace et al, 1997(Wallace et al, , 2003Ashworth et al, 2000;Budge et al, 2000;Thomas et al, 2001;Bispham et al, 2003;Fernandez-Twinn et al, 2003;Bloomfield et al, 2004). Whether glucocorticoids are primarily triggered by foetal nutrient surplus or shortage and act as master regulator orchestrating other endocrine systems is unclear.…”

Session on ‘Obesity’ Adipose tissue development, nutrition in early life and its impact on later obesity

“…The extent to which such a process maybe be reset by the early nutritional environment is unknown, but in species with a long gestation fat cells first appear at about mid gestation (32,33) before total fat mass increases up to term, as the fetus lays down sufficient energy reserves to enable it to meet the cold challenge of the extrauterine environment (15) . Importantly, the net effect is to promote the abundance of brown fat in the offspring (34,35) under thermal or nutritional environments that may act to enhance fetal development. In addition, term infants are born with substantial amounts of subcutaneous fat (36) that increase during lactation, before being mobilised during infancy with its increased energy expenditure in motor development.…”

UCP1 is present in porcine adipose tissue and is responsive to postnatal leptin

“…Protein extraction and western blotting Mitochondria were prepared from 0.2 g frozen adipose tissue as described previously (Budge et al 2000) and the protein content of each preparation determined (Bradford 1976). UCP1 content was measured, with 10 mg mitochondrial protein run on 12% SDS gel, which was transferred onto a membrane (Imobilon, Millipore, Molsheim, France) and incubated for 1 h with the UCP1 antibody (1/10 000 dilution; Schermer et al 1996) followed by 1 h of incubation with a donkey anti-rabbit secondary antibody (1/2000 dilution; Abcam, Paris, France; ab16284).…”