rumenic-acid and 9-11-linoleic-acid

High-density lipoproteins (HDLs) are atheroprotective because of their role in reverse cholesterol transport. The intestine is involved in this process because it synthesizes HDL, removes cholesterol from plasma and excretes it into the lumen. We investigated the role of selected dietary fatty acids on intestinal cholesterol uptake and HDL functionality. Caco-2 monolayers grown on Transwells were supplemented with either palmitic, palmitoleic, oleic, linoleic, docosahexaenoic, eicosapentaenoic, arachidonic or conjugated linoleic acids (CLAs): c9,t11-CLA; t9,t11-CLA; c10,t12-CLA. Cells synthesized HDL in the basolateral compartment for 24 h in the absence or presence of an antibody to SR-BI (aSR-BI), which inhibits its interaction with HDL. Free cholesterol (FC) accumulated to a greater extent in the presence than in the absence of aSR-BI, indicating net uptake of FC by SR-BI. Uptake's efficiency was significantly decreased when cells were treated with c9,t11-CLA relative to the other fatty acids. These differences were associated with lower HDL functionality, since neither SR-BI protein expression nor expression and alternative splicing of other genes involved lipid metabolism were affected. Only INSIG2 expression was decreased, with no increase of its target genes. Increasing pre-β-HDL synthesis, by inducing ABCA1 and adding APOA1, resulted in reduced uptake of FC by SR-BI after c9,t11-CLA treatment, indicating reduced functionality of pre-β-HDL. Conversely, treatment with c9,t11-CLA resulted in a greater uptake of FC and esterified cholesterol from mature HDL. Therefore, Caco-2 monolayers administered c9,t11-CLA produced a nonfunctional pre-β-HDL but took up cholesterol more efficiently via SR-BI from mature HDL.

Topics: Alternative Splicing; Biological Transport; Caco-2 Cells; CD36 Antigens; Cell Polarity; Cholesterol Esters; Cholesterol, Dietary; Cholesterol, HDL; Enterocytes; Enterohepatic Circulation; Gene Expression Regulation; High-Density Lipoproteins, Pre-beta; Humans; Intestinal Absorption; Intracellular Signaling Peptides and Proteins; Kinetics; Linoleic Acids, Conjugated; Lipoproteins, HDL; Membrane Proteins; Stereoisomerism

Conjugated linoleic acid (CLA) is found naturally in meat and dairy products, and represents a potential therapeutic functional nutrient. However, given the discrepancies in isomer composition and concentration, controversy surrounds its proposed antidiabetic, antiobesity effects. This study focused on the effects of CLA-enriched beef (composed predominantly of c9, t11-CLA) in two separate models of metabolic disease: proatherosclerotic ApoE(-/-) mice and diabetic, leptin-deficient ob/ob mice. Animals were fed CLA-enriched beef for 28 days, and markers of the metabolic syndrome and atherosclerosis were assessed. Comprehensive hepatic transcriptomic analysis was completed to understand divergent metabolic effects of CLA. CLA-enriched beef significantly reduced plasma glucose, insulin, nonesterified fatty acid and triacylglycerol and increased adiponectin levels in ob/ob mice. In contrast, plasma lipid profiles and glucose homeostasis deteriorated and promoted atherosclerosis following the CLA-enriched beef diet in ApoE(-/-) mice. Hepatic transcriptomic profiling revealed divergent effects of CLA-enriched beef on insulin signaling and lipogenic pathways, which were adversely affected in ApoE(-/-) mice. This study demonstrated clear divergence in the effects of CLA. CLA-enriched beef improved metabolic flexibility in ob/ob mice, resulting in enhanced insulin sensitivity. However, CLA-enriched diet increased expression of lipogenic genes, resulting in inefficient fatty acid storage which increases lipotoxicity in peripheral organs, and led to profound metabolic dysfunction in ApoE(-/-) mice. While CLA may have potential health effects, in some circumstances, caution must be exercised in presenting this bioactive lipid as a potential functional food for the treatment of metabolic disease.

Topics: Adipose Tissue; Animals; Apolipoproteins E; Atherosclerosis; Cattle; Diet; Disease Models, Animal; Fatty Acids, Unsaturated; Gene Expression Profiling; Gene Expression Regulation; Glucose; Insulin; Leptin; Linoleic Acids, Conjugated; Lipids; Liver; Meat Products; Mice; Mice, Inbred C57BL; Mice, Knockout; Mice, Obese

Conjugated linoleic acid (CLA) has been shown to have a variety of biological activities. However, the effects of CLA on the proliferation of neural progenitor cells (NPCs) are not clear. The objective of this study was to determine the effects of cis-9 trans-11 CLA and trans-10 cis-12 CLA, the predominant individual isomers, on the proliferative activity of NPCs in vitro. Cell counts showed that treatment of NPCs with cis-9 trans-11 CLA increased the cell number in a dose- and time- dependent manner while significant inhibition effect of trans-10 cis-12 CLA was observed. Western blot analysis revealed the elevated expression of cyclin D1 induced by cis-9 trans-11 CLA treatment and the decreased expression of cyclin D1 by trans-10 cis-12 CLA treatment in NPCs. Cyclin D1-siRNA transfection significantly inhibited the promotion of cell proliferation by cis-9 trans-11 CLA. In addition, trans-10 cis-12 CLA inhibited the phosphorylation of protein kinase B (PKB/Akt), while cis-9 trans-11 CLA had no effect on phospho Akt levels. Furthermore, immunofluorescence assay showed that after CLA treatment, the cells retained their functional characteristics of neural progenitors. These results indicated that cis-9 trans-11 CLA can effectively enhance the proliferation of hADSCs. The effect of cis-9 trans-11 CLA may be associated with the up-regulation of cyclin D1 expression.

Topics: Animals; Cell Proliferation; Cells, Cultured; Cyclin D1; Isomerism; Linoleic Acids, Conjugated; Neural Stem Cells; Phosphorylation; Proto-Oncogene Proteins c-akt; Rats; Rats, Sprague-Dawley; RNA Interference; RNA, Small Interfering

Two experiments were undertaken to evaluate the effect on milk and cheese fatty acid composition of feeding different fresh forages to dairy sheep both in winter (experiment 1, growing stage of the forages, early lactating ewes) and in spring (experiment 2, reproduction stage of the forages, midlactating ewes). Four forage species were compared: annual ryegrass (RY, Lolium rigidum Gaudin), sulla (SU, Hedysarum coronarium L.), burr medic (BM, Medicago polymorpha L.), and a daisy forb (CH, Chrysanthemum coronarium L.). The forages were cut twice daily and offered ad libitum to 4 replicate groups of Sarda dairy sheep (groups RY, SU, BM, and CH). The CH forage was particularly rich in linoleic acid in both periods, whereas BM and SU forages were rich in linolenic acid in winter and spring, respectively. Milk fatty acid composition was affected by the forage in both experiments. Milk conjugated linoleic acid and vaccenic acid contents were higher in CH and BM groups (winter) and CH group (spring) than in the other groups. No differences were observed when comparing fatty acid profile between milk, 1-d-old cheeses, and 60-d-old cheeses within experimental groups, suggesting that the fatty acid recovery rates during cheese making and ripening were not affected by the feeding regimens. After stepwise discriminant analyses of the pooled data, the milks and cheeses sourced in the different feeding regimens differed among them. Based on these results, we conclude that it is possible to manipulate the fatty acid profile of sheep dairy produce to maximize the content of beneficial fatty acids by the use of appropriate fresh forage-based regimens.

Topics: alpha-Linolenic Acid; Animals; Cheese; Chrysanthemum; Diet; Fabaceae; Fatty Acids; Female; Food Handling; Lactation; Linoleic Acid; Linoleic Acids, Conjugated; Lolium; Medicago; Mediterranean Region; Milk; Oleic Acids; Seasons; Sheep