Intrauterine growth restriction in piglets modulates postnatal immune function and hepatic transcriptional responses independently of energy intake
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Intrauterine growth restriction in piglets modulates postnatal immune function and hepatic transcriptional responses independently of energy intake. / Amdi, C.; Larsen, C.; Jensen, K. M. R.; Tange, E. Ø.; Sato, H.; Williams, A. R.
In: Frontiers in Physiology, Vol. 14, 1254958, 2023.Research output: Contribution to journal › Journal article › Research › peer-review
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T1 - Intrauterine growth restriction in piglets modulates postnatal immune function and hepatic transcriptional responses independently of energy intake
AU - Amdi, C.
AU - Larsen, C.
AU - Jensen, K. M. R.
AU - Tange, E. Ø.
AU - Sato, H.
AU - Williams, A. R.
N1 - Publisher Copyright: Copyright © 2023 Amdi, Larsen, Jensen, Tange, Sato and Williams.
PY - 2023
Y1 - 2023
N2 - Introduction: Insufficient prenatal nutrition can affect fetal development and lead to intrauterine growth restriction (IUGR). The aim of this study was to investigate hepatic transcriptional responses and innate immune function in piglets suffering from IUGR compared to normal-sized piglets at 3 days of age and explore whether the provision of an energy-rich supplement at birth could modulate these parameters. Methods: A total of 68 piglets were included in the study. Peripheral blood mononuclear cells were harvested for LPS stimulation, and organs were harvested post-mortem to quantify relative weights. Liver tissue was utilized for RNA sequencing coupled with gene-set enrichment analysis. Results: IUGR resulted in increased expression of genes such as PDK4 and substantial alterations in transcriptional pathways related to metabolic activity (e.g., citric acid and Krebs cycles), but these changes were equivalent in piglets given an energy-rich supplement or not. Transcriptomic analysis and serum biochemistry suggested altered glucose metabolism and a shift toward oxidation of fatty acids. IUGR piglets also exhibited suppression of genes related to innate immune function (e.g., CXCL12) and pathways related to cell proliferation (e.g., WNT and PDGF signaling). Moreover, they produced less IL-1β in response to LPS stimulation and had lower levels of blood eosinophils than normal-sized piglets. Discussion: Taken together, our results indicate that IUGR results in early-life alterations in metabolism and immunity that may not be easily restored by the provision of exogenous energy supplementation.
AB - Introduction: Insufficient prenatal nutrition can affect fetal development and lead to intrauterine growth restriction (IUGR). The aim of this study was to investigate hepatic transcriptional responses and innate immune function in piglets suffering from IUGR compared to normal-sized piglets at 3 days of age and explore whether the provision of an energy-rich supplement at birth could modulate these parameters. Methods: A total of 68 piglets were included in the study. Peripheral blood mononuclear cells were harvested for LPS stimulation, and organs were harvested post-mortem to quantify relative weights. Liver tissue was utilized for RNA sequencing coupled with gene-set enrichment analysis. Results: IUGR resulted in increased expression of genes such as PDK4 and substantial alterations in transcriptional pathways related to metabolic activity (e.g., citric acid and Krebs cycles), but these changes were equivalent in piglets given an energy-rich supplement or not. Transcriptomic analysis and serum biochemistry suggested altered glucose metabolism and a shift toward oxidation of fatty acids. IUGR piglets also exhibited suppression of genes related to innate immune function (e.g., CXCL12) and pathways related to cell proliferation (e.g., WNT and PDGF signaling). Moreover, they produced less IL-1β in response to LPS stimulation and had lower levels of blood eosinophils than normal-sized piglets. Discussion: Taken together, our results indicate that IUGR results in early-life alterations in metabolism and immunity that may not be easily restored by the provision of exogenous energy supplementation.
KW - energy supplement
KW - fetal development
KW - intrauterine growth restriction
KW - liver metabolism
KW - LPS challenge
KW - physiology
U2 - 10.3389/fphys.2023.1254958
DO - 10.3389/fphys.2023.1254958
M3 - Journal article
C2 - 37916220
AN - SCOPUS:85175077072
VL - 14
JO - Frontiers in Physiology
JF - Frontiers in Physiology
SN - 1664-042X
M1 - 1254958
ER -
ID: 391499990