Nutritional properties of dietary omega-3-enriched phospholipids

Dietary fatty acids regulate several physiological functions. However, to exert their properties, they have to be present in the diet in an optimal balance. Particular attention has been focused on tissue highly polyunsaturated fatty acids (HPUFAs) n-6/n-3 ratio, influenced by the type and the esterified form of dietary fatty acids. Dietary EPA and DHA when esterified to phospholipids (PLs) are more efficiently incorporated into tissue PLs and seem to possess peculiar properties through specific mechanism(s) of action, such as the capacity to affect endocannabinoid biosynthesis at much lower doses than EPA and DHA in triglyceride form, probably because of the above mentioned higher incorporation into tissue PLs. Downregulation of the endocannabinoid system seems to mediate the positive effects exerted by omega-3-enriched PLs on several parameters of metabolic syndrome. PLs are one of the major dietary forms of EPA and DHA we are exposed to with the everyday diet; therefore, it is not surprising that it guarantees an effective EPA and DHA nutritional activity. Future studies should address whether EPA and DHA in PL form are also more effective than other formulations in ameliorating other pathological conditions where n-3 HPUFAs seem to exert beneficial activities such as cancer and psychiatric disorders

Metabolic interactions between vitamin A and conjugated linoleic acid

Lipid-soluble molecules share several aspects of their physiology due to their common adaptations to a hydrophilic environment, and may interact to regulate their action in a tissue-specific manner. Dietary conjugated linoleic acid (CLA) is a fatty acid with a conjugated diene structure that is found in low concentrations in ruminant products and available as a nutritional supplement. CLA has been shown to increase tissue levels of retinol (vitamin A alcohol) and its sole specific circulating carrier protein retinol-binding protein (RBP or RBP4). However, the precise mechanism of this action has not been elucidated yet. Here, we provide a summary of the current knowledge in this specific area of research and speculate that retinol and CLA may compete for catabolic pathways modulated by the activity of PPAR- and RXR heterodimer. We also present preliminary data that may position PPAR- at the crossroads between the metabolism of lipids and vitamin

Anti-Inflammatory Effect of Beta-Caryophyllene Mediated by the Involvement of TRPV1, BDNF and trkB in the Rat Cerebral Cortex after Hypoperfusion/Reperfusion

We have previously shown that bilateral common carotid artery occlusion followed by reperfusion (BCCAO/R) is a model to study early hypoperfusion/reperfusion-induced changes in biomarkers of the tissue physiological response to oxidative stress and inflammation. Thus in this study, we investigate with immunochemical assays if a single dose of beta-caryophyllene (BCP), administered before the BCCAO/R, can modulate the TRPV1, BDNF, and trkB receptor in the brain cortex; the glial markers GFAP and Iba1 were also examined. Frontal and temporal-occipital cortical regions were analyzed in two groups of male rats, sham-operated and submitted to BCCAO/R. Six hours before surgery, one group was gavage fed a dose of BCP (40 mg/per rat in 300 mu L of sunflower oil), the other was pre-treated with the vehicle alone. Western blot analysis showed that, in the frontal cortex of vehicle-treated rats, the BCCAO/R caused a TRPV1 decrease, an increment of trkB and GFAP, no change in BDNF and Iba1. The BCP treatment caused a decrease of BDNF and an increase of trkB levels in both sham and BCCAO/R conditions while inducing opposite changes in the case of TRPV1, whose levels became higher in BCCAO/R and lower in sham conditions. Present results highlight the role of BCP in modulating early events of the cerebral inflammation triggered by the BCCAO/R through the regulation of TRPV1 and the BDNF-trkB system

Conjugated Linoleic Acid and Brain Metabolism: A Possible Anti-Neuroinflammatory Role Mediated by PPARα Activation

Fatty acids play a crucial role in the brain as specific receptor ligands and as precursors of bioactive metabolites. Conjugated linoleic acid (CLA), a group of positional and geometric isomers of linoleic acid (LA, 18:2 n-6) present in meat and dairy products of ruminants and synthesized endogenously in non-ruminants and humans, has been shown to possess different nutritional properties associated with health benefits. Its ability to bind to peroxisome proliferator-activated receptor (PPAR) α, a nuclear receptor key regulator of fatty acid metabolism and inflammatory responses, partly mediates these beneficial effects. CLA is incorporated and metabolized into brain tissue where induces the biosynthesis of endogenous PPAR α ligands palmitoylethanolamide (PEA) and oleoylethanolamide (OEA), likely through a positive feedback mechanism where PPAR α activation sustains its own cellular effects through ligand biosynthesis. In addition to PPAR α, PEA and OEA may as well bind to other receptors such as TRPV1, further extending CLA own anti-neuroinflammatory actions. Future studies are needed to investigate whether dietary CLA may exert antiinflammatory activity, particularly in the setting of neurodegenerative diseases and neuropsychiatric disorders with a neuroinflammatory basis

Dietary triacylglycerols with palmitic acid in the sn-2 position modulate levels of N-acylethanolamides in rat tissues

BACKGROUND: Several evidences suggest that the position of palmitic acid (PA) in dietary triacylglycerol (TAG) influences different biological functions. We aimed at evaluating whether dietary fat with highly enriched (87%) PA in sn-2 position (Hsn-2 PA), by increasing PA incorporation into tissue phospholipids (PL), modifies fatty acid profile and biosynthesis of fatty acid-derived bioactive lipids, such as endocannabinoids and their congeners. STUDY DESIGN: Rats were fed for 5 weeks diets containing Hsn-2 PA or fat with PA randomly distributed in TAG with 18.8% PA in sn-2 position (Lsn-2 PA), and similar total PA concentration. Fatty acid profile in different lipid fractions, endocannabinoids and congeners were measured in intestine, liver, visceral adipose tissue, muscle and brain. RESULTS: Rats on Hsn-2 PA diet had lower levels of anandamide with concomitant increase of its congener palmitoylethanolamide and its precursor PA into visceral adipose tissue phospholipids. In addition, we found an increase of oleoylethanolamide, an avid PPAR alpha ligand, in liver, muscle and brain, associated to higher levels of its precursor oleic acid in liver and muscle, probably derived by elongation and further delta 9 desaturation of PA. Changes in endocannabinoids and congeners were associated to a decrease of circulating TNF alpha after LPS challenge, and to an improved feed efficiency. CONCLUSIONS: Dietary Hsn-2 PA, by modifying endocannabinoids and congeners biosynthesis in different tissues may potentially concur in the physiological regulation of energy metabolism, brain function and body fat distribution

Intake of palmitic acid and its association with metabolic flexibility in middle-aged individuals: a preliminary study

Objective: This study aimed to assess the relationship between dietary palmitic acid (PA) intake and its association with body fat deposition and metabolic flexibility (MF) in middle-aged healthy individuals. Methods: Fifteen healthy participants (n = 15; 6 males, 9 females) with a mean age of 54 were enlisted. They were subjected to graded exercise tests using a cycle ergometer coupled with a calorimeter. Respiratory gas exchange was evaluated to determine two MF parameters. First, the MF index was derived by multiplying peak fatty acid oxidation (PFO) per kg of fat-free mass (FFM) with the percentage of VO2max at PFO. The second parameter, peak energy substrates’ oxidation (aka PESO), was computed by aggregating the kilocalories from PFO and peak carbohydrate oxidation, normalized per kg FFM. Dietary intake was gauged using a 7-day dietary record. Spearman’s regression was employed to analyze the association between dietary intake of specific fat classes, PA, MF parameters, and body fat percentage. Results: Preliminary results demonstrate that dietary saturated fatty acids (SFA) within physiological limits correlate with enhanced substrate oxidation capacity. This suggests augmented MF in middle-aged subjects. Among dietary SFA, PA was identified as the primary factor in this favorable correlation. Conclusions: Our initial observations, even though preliminary, strongly suggest a beneficial association between PA intake, MF, and body fat percentage. This underscores the potential nutritional importance of PA in promoting MF

Physiological response to lipid peroxidation in ischemia and reperfusion during carotid endarterectomy

<p>Abstract</p> <p>Background</p> <p>In this study we aimed to assess lipid peroxidation during carotid endarterectomy by the formation of PUFA hydroperoxides (PUFAHP) and isoprostanes (IP) and concomitant peroxisomal beta-oxidation as a physiological mechanism to limit their concentration. Two markers of peroxisomal beta oxidation have been evaluated, formation of 2,3 dinor from IP and conjugated esadecadienoic acid (CD 16:2) from peroxisomal beta-oxidation of conjugated linoleic acid (CLA), an unusual fatty acid present in small concentration in our diet and preferentially beta-oxidised in peroxisomes.</p> <p>The study was conducted on 30 patients undergoing carotid endarterectomy. Blood samplings were performed before, during endarterectomy in the "ischemic phase", and 30 seconds, 30 minutes and 2 hours after reperfusion.</p> <p>Results</p> <p>The results showed that PUFAHP increased significantly after 30 min of reperfusion in patients with controlateral stenosis > 50%, and steeply decreased after 2 hour of reperfusion. Interestingly, IP increased in a similar fashion of PUFAHP but never significantly. Both ratios CD16:2/CLA and DIN/IP also increased significantly after 30 min of reperfusion to decrease thereafter.</p> <p>Conclusions</p> <p>Our data show that lipid peroxidation takes place only in patients with high controlateral stenosis and within 2 hours occurs a physiological response aimed to decrease IP and PUFAHP by increasing their catabolism in peroxisomes.</p

Identification of metabolic biomarkers of chronic vagus nerve stimulation (VNS) in subjects with drug-resistant epilepsy (DRE)

Neuromodulation by means of vagus nerve stimulation (VNS) therapy, reduces seizure frequency and improves quality of life in subjects with drug-resistant epilepsy (DRE), yet its molecular mechanism remains unclear. This study investigates the impact of chronic VNS on lipid bioactive metabolites and fatty acids (FA) in the plasma and red blood cells of seven subjects with DRE. By measuring expression levels of peroxisome proliferator-activated receptor alpha (PPAR alpha) and sirtuin1 (SIRT1) genes-key regulators in energy and lipid metabolism-and lipid profiles before and after various stages of VNS, this study identifies potential mechanisms by which VNS may reduce seizure frequency. Blood samples collected before VNS device implantation, after acute VNS stimulus, and following gradual intensity increments up to therapeutic levels revealed that VNS increases SIRT1 and PPAR alpha expression and erythrocyte concentrations of PPAR alpha ligands. Additionally, we observe reduced de novo lipogenesis biomarkers in erythrocytes, indicating that VNS may influence systemic lipid and energy metabolism. Our findings suggest that VNS could enhance neuronal function by modulating energy metabolism, thus potentially reducing seizure frequency in subjects with DRE. Future research targeting SIRT1 and PPAR alpha may provide innovative therapeutic strategies for managing DRE

Participants with Normal Weight or with Obesity Show Different Relationships of 6-n-Propylthiouracil (PROP) Taster Status with BMI and Plasma Endocannabinoids

Reduced taste sensitivity to 6-n-propylthiouracil (PROP), a genetic trait regarded as a general index for oral chemosensory perception, has been associated with a calorie-rich food preference and lower circulating endocannabinoid levels in participants with normal weight (NW), which suggests an adaptive mechanism to maintain a lean phenotype. In this study, we assessed whether participants with obesity (OB) show different patterns of plasma endocannabinoids and lipid metabolism biomarkers from those of NW, with further categorization based on their PROP sensitivity. NW and OB were classified by their PROP taster status as non-tasters (NT), medium-tasters (MT) and supertasters (ST). The blood samples were analysed for plasma endocannabinoids, nonesterified fatty acids (NEFA) and retinol, which have been associated to metabolic syndrome. In OB, we found a higher BMI and lower circulating endocannabinoids in ST vs. OB NT. However, OB ST showed lower circulating NEFA and retinol levels, which suggested a more favourable lipid metabolism and body fat distribution than those of OB NT. We confirmed lower plasma endocannabinoid levels in NW NT than in NW ST. These data suggest that PROP taste sensitivity determines metabolic changes and ultimately body mass composition differently in OB and NW