Nutrient-intake-level-dependent regulation of intestinal development in newborn intrauterine growth-restricted piglets via glucagon-like peptide-2

Abstract

The objective of the present study was to investigate the intestinal development of newborn intrauterine growth-restricted (IUGR) piglets subjected to normal nutrient intake (NNI) or restricted nutrient intake (RNI). Newborn normal birth weight (NBW) and IUGR piglets were allotted to NNI or RNI levels for 4 weeks from day 8 postnatal. IUGR piglets receiving NNI had similar growth performance compared with that of NBW piglets. Small intestine length and villous height were greater in IUGR piglets fed the NNI than that of piglets fed the RNI. Lactase activity was increased in piglets fed the NNI compared with piglets fed the RNI. Absorptive function, represented by active glucose transport by the Ussing chamber method and messenger RNA (mRNA) expressions of two main intestinal glucose transporters, Na + -dependent glucose transporter 1 ( SGLT1) and glucose transporter 2 ( GLUT2), were greater in IUGR piglets fed the NNI compared with piglets fed the RNI regimen. The apoptotic process, characterized by caspase-3 activity (a sign of activated apoptotic cells) and mRNA expressions of p53 (pro-apoptotic), bcl-2-like protein 4 (Bax) (pro-apoptotic) and B-cell lymphoma-2 (Bcl-2) (anti-apoptotic), were improved in IUGR piglets fed the NNI regimen. To test the hypothesis that improvements in intestinal development of IUGR piglets fed NNI might be mediated through circulating glucagon-like peptide-2 (GLP-2), GLP-2 was injected subcutaneously to IUGR piglets fed the RNI from day 8 to day 15 postnatal. Although the intestinal development of IUGR piglets fed the RNI regimen was suppressed compared with those fed the NNI regimen, an exogenous injection of GLP-2 was able to bring intestinal development to similar levels as NNI-fed IUGR piglets. Collectively, our results demonstrate that IUGR neonates that have NNI levels could improve intestinal function via the regulation of GLP-2.

Catch-up Growth in Intrauterine Growth-restricted Piglets Associated with the Return of Pancreatic and Intestinal Functions via Porcine Glucagon-like peptide-2 Microspheres

“…From days 15 to 26, the BWs of animals treated with pGLP-2 microspheres were significantly higher than those of piglets in the control IUGR group. Importantly, the weaning weight in day 26 of piglets in the pGLP-2 group catched up to the BW of the normal birth weight group, as revealed by Liu et al [11].…”

“…week after birth. Liu et al [11] demonstrated significantly increased the villous height of IUGR piglets injected with GLP-2 compared with the control group under the condition of restricted nutrient intake.…”

“…D'Inca et al [4] also demonstrated that the IUGR and normal birth weight (NBW) piglets had similar relative growth rates during the first 5 days of life. Liu et al [11] indicated that the compensatory growth of IUGR piglets is the result of an adequate nutrient intake level. Whether this kind of catch-up in BW would increase the risk of metabolic disorders in the whole growth period because of the mismatch of pre-and postnatal nutrition remains unclear.…”

“…As a gastrointestinal growth factor, the therapeutic effect of pGLP-2 on intestinal dysfunction and damage in weaning and diarrheal diseases of piglets has been demonstrated [6,9]. Enteral nutrient intake can increase the plasma GLP-2 concentration [11,23] and facilitate the intestinal development of newborn piglets through improved intestinal cell survival and proliferation [24]. The main nutrient transporters mediating the intestinal uptake of glucose in newborn piglets are SGLT1 and GLUT2.…”

A high nutrient dense diet alters hypothalamic gene expressions to influence energy intake in pigs born with low birth weight

“…Chronically increased amino acids during the late phase of gestation improved insulin secretion of islet cell in growth-restricted fetal sheep 5 . When LBW piglets received a similar level of nutrition as piglets born with normal birth weight (NBW), they had equal growth performance compared with that of NBW piglets 6 . Low birth weight pigs provided with a high quality and expensive dietary regime might ensure maximum growth and increased profitability 7 .…”