Sialic Acid Utilisation and Synthesis in the Neonatal Rat Revisited

Background: Milk is the sole source of nutrients for neonatal mammals and is generally considered to have co-evolved with the developmental needs of the suckling newborn. One evolutionary conserved constituent of milk and present on many glycoconjugates is sialic acid. The brain and colon are major sites of sialic acid display and together with the liver also of synthesis. Methodology/Principal Findings: In this study we examined in rats the relationship between the sialic acid content of milk and the uptake, utilization and synthesis of sialic acid in suckling pups. In rat milk sialic acid was found primarily as 39sialyllactose and at highest levels between 3 and 10 days postpartum and that decreased towards weaning. In the liver of suckling pups sialic acid synthesis paralleled the increase in milk sialic acid reaching and keeping maximum activity from postnatal day 5 onwards. In the colon, gene expression profiles suggested that a switch from sialic acid uptake and catabolism towards sialic acid synthesis and utilization occurred that mirrored the change of sialic acid in milk from high to low expression. In brain sialic acid related gene expression profiles did not change to any great extent during the suckling period. Conclusions/Significance: Our results support the views that (i) when milk sialic acid levels are high, in the colon this sialic acid is catabolized to GlcNAc that in turn may be used as such or used as substrate for sialic acid synthesis and (ii) when milk sialic acid levels are low the endogenous sialic acid synthetic machinery in colon is activated

Consequences of Exchanging Carbohydrates for Proteins in the Cholesterol Metabolism of Mice Fed a High-fat Diet

Consumption of low-carbohydrate, high-protein, high-fat diets lead to rapid weight loss but the cardioprotective effects of these diets have been questioned. We examined the impact of high-protein and high-fat diets on cholesterol metabolism by comparing the plasma cholesterol and the expression of cholesterol biosynthesis genes in the liver of mice fed a high-fat (HF) diet that has a high (H) or a low (L) protein-to-carbohydrate (P/C) ratio. H-P/C-HF feeding, compared with L-P/C-HF feeding, decreased plasma total cholesterol and increased HDL cholesterol concentrations at 4-wk. Interestingly, the expression of genes involved in hepatic steroid biosynthesis responded to an increased dietary P/C ratio by first down-regulation (2-d) followed by later up-regulation at 4-wk, and the temporal gene expression patterns were connected to the putative activity of SREBF1 and 2. In contrast, Cyp7a1, the gene responsible for the conversion of cholesterol to bile acids, was consistently up-regulated in the H-P/C-HF liver regardless of feeding duration. Over expression of Cyp7a1 after 2-d and 4-wk H-P/C-HF feeding was connected to two unique sets of transcription regulators. At both time points, up-regulation of the Cyp7a1 gene could be explained by enhanced activations and reduced suppressions of multiple transcription regulators. In conclusion, we demonstrated that the hypocholesterolemic effect of H-P/C-HF feeding coincided with orchestrated changes of gene expressions in lipid metabolic pathways in the liver of mice. Based on these results, we hypothesize that the cholesterol lowering effect of high-protein feeding is associated with enhanced bile acid production but clinical validation is warranted. (246 words

Sialyllactose and sialic acid levels in plasma and urine of suckling rat pups.

<p>A) Plasma 3′sialyllactose (3SL) and B) urine 3SL and free sialic acid (NeuAc) levels were determined in pups throughout the suckling period. Mean and SD are shown (N = 6). The bar above each x-axis indicates the relative level of sialic acid in milk (low, open and high, filled).</p

Colon gene expression levels in suckling rat pups.

<p>A–F) Filled symbols apply to the left scale bar and open symbols to the right scale bar. Mean and SD are shown (N = 6, except PND-1 N = 5). The bar above each x-axis indicates the relative level of sialic acid in milk (low, open and high, filled).</p

Colon gene expression levels in suckling rat pups.

<p>A–C) Filled symbols apply to the left scale bar and open symbols to the right scale bar. Mean and SD are shown (N = 6, except PND-1 N = 5). The bar above each x-axis indicates the relative level of sialic acid in milk (low, open and high, filled).</p

Gene expression levels of <i>GNE</i> and <i>Slc17a5</i>.

<p>A) Relative <i>GNE</i> (sialic acid synthesis) and <i>Slc17a5</i> (sialic acid uptake) expression levels in the central nervous system (CNS), liver and small and large intestine throughout development and aging in the mouse, rat and human. (E, embryonic; d, day; w, week; y, year; dashed line, not determined). B) <i>GNE</i> and <i>Slc17a5</i> expression in the intestine of 17 and 21 day old rat pups. The data was extracted from the Gene Expression Omnibus repository at <a href="http://www.ncbi.nlm.nih.gov/sites/GDSbrowser?acc=GDS1273" target="_blank">http://www.ncbi.nlm.nih.gov/sites/GDSbrowser?acc=GDS1273</a>. Mean and SD are shown; N = 3, except PND17 colon, N = 2.</p