Pigs Fed Cholesterol Neonatally Have Increased Cerebrum Cholesterol as Young Adults

Abstract

Sixty-eight female neonatal pigs selected for seven (Experiment 1) or eight (Experiment 2) generations for high (HG) or low (LG) plasma cholesterol were used to test the hypothesis that neonatal dietary cholesterol fed during the first 4 or 8 wk of postnatal life increases the cholesterol content of the cerebrum in young adulthood following free access to a high-fat (15%), high-cholesterol (0.5%) diet from 8 to 20 or 24 wk of age. Pigs were removed from their dams at 1 d of age and given free access to a sow-milk replacer diet containing 9.5% coconut fat and 0 or 0.5 % cholesterol. All pigs (except four HG and four LG pigs in Experiment 2, which were deprived of cholesterol throughout the study) were fed the high-fat, high-cholesterol diet from 8 wk to termination at 20 or 24 wk of age. Cerebrum weight and cholesterol concentration were higher in pigs fed cholesterol neonatally than in those deprived of cholesterol neonatally in both experiments, but weight and cholesterol concentration were unaffected by genetic line. Cholesterol concentrations in longissimus and semitendinosus muscles and in subcutaneous fat were unaffected by diet or genetic line. We conclude that dietary cholesterol deprivation during the first 4 to 8 wk of life in piglets is associated with lower cholesterol concentration and total content in the young adult cerebrum than in pigs supplemented with cholesterol in early life. These data support previous observations and suggest the possibility of a metabolic need for neonatal dietary cholesterol in normal brain development.

Brainstem Concentrations of Cholesterol are not Influenced by Genetic Ablation of the Low-Density Lipoprotein Receptor

“…In some mammals such as the pig, the LDLr seems to be involved in cholesterol uptake, because changes in circulating cholesterol levels during early development alter cholesterol concentrations in the cerebellum [23,24]. Thus, the LDLr may have played a role in cholesterol transport into older brain regions such as the brainstem and cerebellum, particularly during early development.…”

Dietary supplementation with cholesterol and docosahexaenoic acid affects concentrations of amino acids in tissues of young pigs

“…They were assigned randomly within litter to one of four nutritionally adequate sow-milk replacer formulas containing: (1) 0.0% cholesterol and DHA, (2) 0.20% cholesterol and zero DHA, (3) zero cholesterol and 0.2% DHA, or (4) 0.2% cholesterol and 0.2% DHA (Li et al 2008). The doses of cholesterol and DHA were based on the previous studies (Boleman et al 1998; Pond et al 2008). The experiment was performed in four blocks of four pigs each (total of 16 pigs).…”

“…Particularly, an increase in plasma concentrations of cholesterol, which is an essential constituent of all animal cells (especially of brain) and abundant in milk, is positively associated with enhancement of cerebrum weight gain and behavioral development (Boleman et al 1998; Pond et al 2008). Additionally, docosahexaenoic acid (DHA) is a component of complex lipids in membranes, nerve insulation, as well as a precursor for signaling molecules (including prostaglandins).…”

Role of apolipoprotein E4 in protecting children against early childhood diarrhea outcomes and implications for later development

“…These new findings suggest that APOE polymorphisms might have a different role during early development and aging. We hypothesize that enriched cholesterol diets and increased cholesterol absorption, which is mostly regulated by apoE isoforms early in life [33] in weanling malnourished children, might have a critical role during long-term brain maturation [34,35].…”

“…NO is critical for synapses [100][101][102][103] (b) Increasing cholesterol availability to the developing brain, cholesterol as a glial synaptogenic factor and indirect trigger for myelination in the brain [34,104,28,105,27] Infection (a) ApoE4 by downregulating LDL receptors may starve enteric pathogens from cholesterol and block proliferation. The LDL-receptor pathway is also highly conserved across the animal kingdom [106][107][108][109][110] (b) ApoE is secreted in a polarized manner by enterocytes, increased by 25-OHcholesterol and decreased by LPS through an LXR α /RXR independent signaling pathway [47].…”