Abstract Background Evidence indicates that birth weight and neonatal nutrition have lifelong effects. Animal models are required to improve our understanding of these factors. Objective Develop and validate a swine model of birth weight and neonatal undernutrition. Methods At birth, a total of 112 piglets were identified as low (LBW, 1.22 ± 0.28 kg) or normal birth weight (NBW, 1.70 ± 0.27 kg). From d 3 to weaning (d 28), piglets received normal nutrition (NN) or were nutrient restricted (RN) via intermittent suckling, where piglets were isolated from the sow for 6 h/d. Following weaning, pigs were fed a common diet for 28 d. Body weight (BW) was determined for the duration of the study. On d 28 and 56, empty carcass and viscera and individual organ weight were determined in 8 pigs/treatment. Results LBW pigs remained smaller than NBW pigs, regardless of nutrient restriction (P < 0.05). Within birth weight category, RN reduced BW by d 7 after birth, which was maintained until weaning (P < 0.05), however, 7 d post-weaning there was no difference in BW due to RN (P > 0.05). At weaning, empty carcass, viscera, heart, liver, and lung weights were lower in LBW vs. NBW, while empty carcass, heart, small intestine, liver, kidneys, lung, and spleen weights were lower in RN vs. NN (P < 0.05). Brain weight was highest in NBW-NN and lowest in NBW-RN, with LBW intermediate, regardless of nutrient restriction (P < 0.05). Post-weaning, LBW had lower empty carcass, viscera, heart, stomach, large intestine, liver, and kidney weights vs. NBW, while RN had a higher small intestine weight vs. NN (P < 0.05). Conclusion Intermittent suckling is an effective means of inducing nutrient restriction in a swine model.

We determined the impact of creep feed provision and type on pre- and post-weaning growth performance of piglets. At 2 weeks post-farrow, litters (n=50) were given no creep feed or provided a simple creep feed, a complex creep feed, or both until weaning at ~28 d. Creep feed, regardless of type, resulted in increased growth (P < 0.05) of piglets in the final week pre-weaning and immediate week post-weaning, which was not maintained at the end of the nursery period. Piglets showed no preference for creep feed type (P > 0.05).

Nucleobindin-derived peptides, nesfatin-1 [NESF-1] and nesfatin-1-like-peptide [NLP] have diverse roles in endocrine and metabolic regulation. While both peptides showed a stimulatory effect on the synthesis of POMC, the ACTH precursor in mouse corticotrophs, whether NESF-1 and NLP have any direct effect on glucocorticoid [GC] synthesis in the adrenal cortex remains unknown. The main aim of this study was to determine if NESF-1 and/or NLP act directly on adrenal cortex cells to regulate cortisol synthesis in vitro. Whether NLP injection affects stress-hormone gene expression in the adrenal gland and pituitary in vivo in mice was also assessed. In addition, cortisol synthetic pathway in Nucb1 knockout [KO] mice was studied. Human adrenal cortical [H295R] cells showed immunoreactivity for both NUCB1/NLP and NUCB2/NESF-1 using immunohistochemistry. NLP and NESF-1 decreased the expression of steroidogenic enzymes, cortisol synthesis and release through the AC/PKA/CREB pathway in H295R cells. Similarly, intraperitoneal injection of NLP in mice decreased the expression of enzymes involved in GC synthesis in the adrenal gland while increasing the expression of Pomc, Pcsk1 and Crhr1 in the pituitary. Moreover, the Mc2r mRNA level was enhanced in the adrenal gland samples of NLP injected mice. However, the global genetic disruption in Nucb1 did not affect most steroidogenic enzyme mRNAs, and Pomc, Pcsk2 and Crhr1 mRNAs in mice adrenal gland and pituitary gland, respectively. Collectively, these data provide the first evidence that NLP and NESF-1 directly decreased cortisol synthesis and secretion in vitro. NUCB peptides still might play its stimulatory effect on GC synthesis and secretion through their positive effects on ACTH-MC2R pathway in the pituitary.