Influences of maternal nutrient restriction and arginine supplementation on visceral metabolism and hypothalamic circuitry of offspring

Authors: PREZOTTO, LIGIA - Montana State University; THORSON, JENNIFER - Montana State University; BOROWICZ, PAWEL - North Dakota State University; PEINE, JENA - North Dakota State University; BEDENBAUGH, MICHELLE - West Virginia University; HILEMAN, STANLEY - West Virginia University; Lents, Clay; CATON, JOEL - North Dakota State University; SWANSON, KENDALL - North Dakota State University

Submitted to: Domestic Animal Endocrinology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 6/13/2018
Publication Date: 10/1/2018
Publication URL: https://handle.nal.usda.gov/10113/6053951
Citation: Prezotto, L.D., Thorson, J.F., Borowicz, P.P., Peine, J.L., Bedenbaugh, M., Hileman, S.M., Lents, C.A., Caton, J.S., Swanson, K.C. 2018. Influences of maternal nutrient restriction and arginine supplementation on visceral metabolism and hypothalamic circuitry of offspring. Domestic Animal Endocrinology. 65:71-79. https://doi.org/10.1016/j.domaniend.2018.06.001.
DOI: https://doi.org/10.1016/j.domaniend.2018.06.001

Interpretive Summary: Intrauterine growth retardation (IUGR) is a condition marked by restricted growth of the developing fetus when conditions within the uterus are not optimal. There are long-term negative consequences for health and performance in adulthood of a fetus that is born IUGR. Arginine is a nutrient that is important for fetal development and could alleviate some of the negative effects of IUGR. ARS scientists, in collaboration with researchers from North Dakota State University, determined if supplementing arginine to pregnant sheep could counteract some of the long-term effects of undernutrition of the fetus during pregnancy. They discovered that the respiratory quotient, a measure of energy metabolism, in the liver of adult sheep was affected by the nutritional status of their mothers during pregnancy. Supplementing arginine to the mothers during pregnancy normalized energy metabolism in the liver of their adult offspring. Scientists also found that supplementing arginine to pregnant mothers altered some key signals in the brain of their adult offspring that control food intake, suggesting a compensatory mechanism that could impact postnatal growth of IUGR fetuses. Researchers are now focused on how to use this information to improve fetal development and optimize adult health and performance of offspring.

Technical Abstract: Maternal nutrient restriction during gestation can exert long-term negative effects on offspring health and performance. Arginine supplementation may rescue some of the negative effects elicited by maternal nutrient restriction. We tested the hypothesis that maternal arginine supplementation during gestation would rescue deleterious effects of nutrient restriction on in vitro O2 consumption in liver and jejunum and hypothalamic protein expression of proopiomelanocortin (POMC), neuropeptide Y (NPY), agouti-related peptide (AgRP), and neuronal nitric oxide synthase (nNOS), and the colocalization of nNOS and active phosphor-signal transducer and activator of transcription 3 (pSTAT3) in female offspring. Multiparous ewes were assigned to dietary treatment at 54 d of gestation; 100% of requirements (Con), 60% of control (Res), or Res plus rumen-protected arginine (Res-Arg; 180 mg/kg). At parturition, offspring were immediately removed from their dam and placed on a common diet. At 54 ± 4 d of age, female lambs (n = 6 per treatment) were weighed and the liver and jejunum weighed and samples collected for in vitro measurement of O2 consumption. The hypothalamus was collected to determine protein expression of POMC, NPY, AgRP, and nNOS, and the colocalization of nNOS and pSTAT3 (n = 3, 4, and 4 for Con, Res, and Res-Arg, respectively). Hepatic consumption of O2 in vitro was decreased (P = 0.04) in the Res and Res-Arg group compared with Con. Intensity of staining for NPY containing fibers tended to decrease (P = 0.10) in Res and Res-Arg compared with Con. Number of POMC neuronal cells in the arcuate nucleus (ARC) of the hypothalamus decreased (P = 0.03) in the Res group compared with Res-Arg. These observations demonstrate that maternal nutrient restriction decreases energy utilization in the liver and number of POMC cells in the ARC of offspring. Supplementation of arginine to the gestating ewe failed to influence hepatic use of energy in lambs from Res ewes. Numbers of POMC-containing cells were increased in the ARC in lambs from ewes restricted to 60% of nutritional requirements and supplemented with rumen-protected arginine, potentially influencing feeding behavior and hepatic energy metabolism.