Dietary triacyglycerols rich in sn-2 palmitate alter post-prandial lipoprotein and unesterified fatty acids in term infants.

Human milk TAG contain 20-25% 16:0, with over 70% of the 16:0 at the TAG sn-2 position. The benefits of TAG sn-2 16:0 have been ascribed to reducing 16:0 excretion as insoluble fatty acid soaps. This study builds on knowledge that infants conserve milk TG sn-2 16:0 post-absorption. Comparison of plasma lipids from 120 day old infants fed formula containing 25-27% 16:0 with 29% 16:0 or 5% 16:0 at the TAG sn-2 position showed higher formula sn-2 16:0 led to lower 18:1n-9, but higher 18:2n-6 and 22:6n-3 in the infant plasma unesterified fatty acids, higher 18:0 in LDL TAG, and higher apo B and lower apo A-1. TAG-sn-2 16:0 may provide 16:0 in remnant particles for hepatic elongation to 18:0, needed for plasma and tissue phospholipids. We suggest attention to the plasma unesterified fatty acids as possible sources of fatty acids for membrane phospholipid synthesis.

Dietary Ascophyllum nodosum increases urinary excretion of tricarboxylic acid cycle intermediates in male Sprague-dawley rats.

We used a (1)H NMR-based metabonomics approach to examine the physiological effects of the seaweed Ascophyllum nodosum in a mammalian model, assess the dosage level required to elicit a response in the urinary profile, and identify potential toxic effects. Male Sprague-Dawley rats (n = 6/group) were fed a control or 5, 10, or 15% freeze-dried, ground A. nodosum diet for 4 wk. Urine samples were collected 3 times daily (0-4, 4-8, and 8-24 h) prior to feeding experimental diets and, at the end of the study, were profiled using (1)H NMR spectroscopy. Food intake, weight gain, and serum enzyme (alanine transaminase and aspartate transaminase) levels indicated that seaweed diets were well tolerated. The spectral data and principal component analysis (PCA) revealed that rats fed 5, 10, and 15% seaweed diets had increased urinary excretion of citrate, 2-oxoglutarate, succinate, trimethylamine (TMA), TMA-N-oxide, and malonate and decreased excretion of taurine, creatinine, and acetate compared with the controls. In addition, mannitol was detected in the 8- to 24-h urine samples from seaweed-fed rats. Metabolic responses related to ingestion of seaweed polyphenolics and fiber were not observed in the spectral profiles. Increased seaweed concentration in the diet did not increase the magnitude of the rats' response as detected by (1)H NMR. Visual analysis and PCA of the spectral data for serum samples collected at the end of the study did not show diet-related clustering. The lack of toxicity at 15% seaweed incorporation allows the use of this concentration in future A. nodosum intervention studies.

Quercetin 3-glucoside protects neuroblastoma (SH-SY5Y) cells in vitro against oxidative damage by inducing sterol regulatory element-binding protein-2-mediated cholesterol biosynthesis.

The flavonoid quercetin 3-glucoside (Q3G) protected SH-SY5Y, HEK293, and MCF-7 cells against hydrogen peroxide-induced oxidative stress. cDNA microarray studies suggested that Q3G-pretreated cells subjected to oxidative stress up-regulate the expression of genes associated with lipid and cholesterol biosynthesis. Q3G pretreatment elevated both the expression and activation of sterol regulatory element-binding protein-2 (SREBP-2) only in SH-SY5Y cells subjected to oxidative stress. Inhibition of SREBP-2 expression by small interfering RNA or small molecule inhibitors of 2,3-oxidosqualene:lanosterol cyclase or HMG-CoA reductase blocked Q3G-mediated cytoprotection in SH-SY5Y cells. By contrast, Q3G did not protect either HEK293 or MCF-7 cells via this signaling pathway. Moreover, the addition of isopentenyl pyrophosphate rescued SH-SY5Y cells from the inhibitory effect of HMG-CoA reductase inhibition. Last, Q3G pretreatment enhanced the incorporation of [(14)C]acetate into [(14)C]cholesterol in SH-SY5Y cells under oxidative stress. Taken together, these studies suggest a novel mechanism for flavonoid-induced cytoprotection in SH-SY5Y cells involving SREBP-2-mediated sterol synthesis that decreases lipid peroxidation by maintaining membrane integrity in the presence of oxidative stress.

Fatty acid regulation of gene expression: a genomic explanation for the benefits of the mediterranean diet.

The development of obesity and associated insulin resistance involves a multitude of gene products, including proteins involved in lipid synthesis and oxidation, thermogenesis, and cell differentiation. The genes encoding these proteins are in essence the blueprints that we have inherited from our parents. However, what determines the way in which blueprints are interpreted is largely dictated by a collection of environmental factors. The nutrients we consume are among the most influential of these environmental factors. During the early stages of evolutionary development, nutrients functioned as primitive hormonal signals that allowed the early organisms to turn on pathways of synthesis or storage during periods of nutrient deprivation or excess. As single-cell organisms evolved into complex life forms, nutrients continued to be environmental factors that interacted with hormonal signals to govern the expression of genes encoding proteins involved in energy metabolism, cell differentiation, and cell growth. Nutrients govern the tissue content and activity of different proteins by functioning as regulators of gene transcription, nuclear RNA processing, mRNA degradation, and mRNA translation, as well as functioning as posttranslational modifiers of proteins. One dietary constituent that has a strong influence on cell differentiation, growth, and metabolism is fat. The fatty acid component of dietary lipid not only influences hormonal signaling events by modifying membrane lipid composition, but fatty acids have a very strong direct influence on the molecular events that govern gene expression. In this review, we discuss the influence that (n-9), (n-6), and (n-3) fatty acids exert on gene expression in the liver and skeletal muscle and the impact this has on intra- and interorgan partitioning of metabolic fuels.