Brain lipidomics and neurodevelopmental outcomes in intrauterine growth restricted piglets fed dairy or vegetable fat diets

Abstract

Breast milk has neurodevelopmental advantages compared to infant formula, especially in low-birth-weight infants, which may in part relate to the fat source. This study compared neurodevelopmental outcomes in three-day-old normal birth weight (NBW) and intrauterine growth restricted (IUGR) piglets fed a formula diet with either vegetable oil (VEG) or bovine milk fat sources (MILK) for three weeks in a 2 × 2 factorial design. Behavioural tests, lipidomics, MRI and RNA sequencing analyses of plasma and brain tissue were conducted. The absolute levels of 82% and 11% of lipid molecules were different between dietary groups in plasma and hippocampus, respectively. Of the lipid molecules with differential abundance in the hippocampus, the majority were upregulated in MILK versus VEG, and they mainly belonged to the group of glycerophospholipids. Lower absolute brain weights, absolute grey and white matter volumes and behaviour and motor function scores, and higher relative total brain weights were present in IUGR compared to NBW with minor influence of diet. Cognitive function and cerebellar gene expression profiles were similar for dietary and weight groups, and overall only minor interactive effects between diet and birth weight were observed. Overall, we show that the dietary fat source influences the plasma and to a lesser degree the hippocampal lipidome and is unable to improve on IUGR-induced brain structural and functional impairments.

Infant formula containing large, milk phospholipid-coated lipid droplets and dairy lipids affects cognitive performance at school age

“…In line with this, infants consuming an IF containing a mixture of dairy lipids and vegetable oil were shown to have higher erythrocyte n-3 LCPUFAs compared to infants who were fed an IF containing vegetable oil only ( 45 ). Using animal models, several studies confirmed higher n-3 PUFAs in brain tissue as a result of dairy lipid exposure ( 38 , 46 , 47 ), but others did not ( 48 ), and the effects on functional outcomes such as neuroplasticity and cognition appear to be mixed ( 47 , 49 , 50 ). Currently, the evidence is insufficient to confirm a role of sn-2 PA supplementation on infant neurodevelopmental outcomes ( 51 ).…”

Insulin-like growth factor 1 supplementation supports motor coordination and affects myelination in preterm pigs

“…The volume of the right brain hemisphere, white matter, and grey matter were measured by MRI as previously described ( Henriksen et al, 2022a ). Briefly, the entire right hemisphere was immersed in 4% paraformaldehyde in phosphate buffered saline for 24 h at 4°C (PBS; 0.1 M, pH 7.4), rehydrated with PBS for 24 h at 4°C and washed twice with Fomblin (perfluoro-polyether; Solvay, Princeton, New Jersey, USA) to remove the excess fluid and resubmerged in clean Fomblin prior to scanning.…”

“…The imaging protocol used a 3D gradient-spoiled steady state free precession, and the parameters were set to: repetition time = 4.6 ms, echo time = 2.3 ms, number of signals averaged = 10, flip angle = 25°, field of view = 60 mm × 38.4 mm × 25.6 mm, matrix = 300 × 192 × 128, image resolution = 200 μm isotropic, acquisition time = 20 min. The images were bias-field corrected, and segmented as previously described ( Henriksen et al, 2022a ). The volume of white and grey matter was normalized to the total volume of the brain hemisphere.…”