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

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 the 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, the liver and jejunum were weighed, and samples were 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 (mol/min/liver) 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.