Author
Larson, Kate | |
Dekrey, Emilie | |
Roemmich, James | |
GHRIBI, OTHMAN - University Of North Dakota | |
RHEN, TURK - University Of North Dakota |
Submitted to: Journal of Nutritional Biochemistry
Publication Type: Peer Reviewed Journal Publication Acceptance Date: 1/23/2015 Publication Date: 7/1/2015 Publication URL: https://handle.nal.usda.gov/10113/61097 Citation: Claycombe, K.J., Dekrey, E.E., Roemmich, J.N., Ghribi, O., Rhen, T. 2015. Maternal low protein diet causes body weight loss in male, neonate Sprague-Dawley rats involving UCP-1 mediated thermogenesis. Journal of Nutritional Biochemistry. 26(7):729-735. Interpretive Summary: A maternal low protein diet can reduce offspring birth weight which can lead to rapid weight gain of fat tissue during adolescence and into adulthood and increase the risk for insulin resistance. An important regulator of thermogenesis or of body weight, insulin resistance and body temperature is the brown adipose tissue (BAT), thermogenic marker, uncoupling protein-1 (UCP-1). Using a rat model, we found that a maternal low protein diet led to a decrease in male offspring birth weight and an increase in the BAT UCP-1. Additionally, we found that other thermogenic factors that regulate UCP-1, including FNDC5, PRDM16 and PPAR-alpha were also increased. However, a maternal low protein diet did not affect the BAT UCP-1, FNDC5, PRDM16 and PPAR-alpha levels in the placenta or male fetuses. These results indicate that a maternal low protein diet increases the risk for a reduced birth weight by mechanisms increasing thermogenesis in full-term offspring but not by an increase in placental or fetal thermogenesis. Technical Abstract: Brown adipose tissue (BAT) plays an important role in regulating body weight (BW) by modifying thermogenesis. Maternal low protein (LP) diets reduce offspring birth weight. Increased BAT thermogenesis in utero may be one mechanism for the lower BW. However, whether maternal LP nutrition alters BAT thermogenesis and BW of offspring in-utero is not yet known. We fed obese-prone Sprague-Dawley dams 8% low protein (LP) or 20% normal protein (NP) diets for 3 weeks prior to breeding and through pregnancy. BW and gene expression of interscapular BAT (iBAT) thermogenic markers were measured in male fetal (gestation day 18) and neonatal (day 0 or 1) offspring. BW of neonatal LP males was lower than NP males but no difference was observed in females. Gene expression of thermogenic factors UCP-1 and UCP-3 and transcription factors PRDM16 and PPARa in iBAT were 2- to 6-fold greater in LP than NP male neonatal offspring. FNDC5, a precursor of irisin and activator of thermogenesis, was expressed 2-fold greater in neonatal LP iBAT than NP males. However, fetal iBAT UCP-1, PRDM16, PPARa and irisin mRNA did not differ between LP and NP groups. Maternal LP diet had no effects on placental irisin and UCP-2 expression. Deiodinase-2 mRNA expression was correlated with UCP-1 mRNA expression indicating a possible altered thyroid axis regulation of iBAT UCP-1 in male neonates. These results suggest that prenatal protein restriction increases the risk for low BW through mechanisms effecting full-term offspring iBAT thermogenesis but not greatly altering fetal iBAT or placental thermogenesis. |