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

The Oral History of Vic Salerno

<p>AEA, anandamide; PEA, palmitoylethanolamide; OEA, oleoylethanolamide; 2-AG, 2-arachidonoylglycerol. Values are means ± SD, n = 10.</p><p>* P< 0.05.</p><p>Visceral adipose tissue N-Acylethanolamides (NAEs), 2-AG and fatty acid concentrations in phospholipids (PL), triacylglycerols (TAG) and non esterified fatty acids (NEFA), in rats fed Lsn-2 PA or Hsn-2 PA for 5 weeks.</p

Bifidobacterium breve with a-linolenic acid alters the composition, distribution and transcription factor activity associated with metabolism and absorption of fat

This study focused on the mechanisms that fatty acid conjugating strains - Bifidobacterium breve NCIMB 702258 and Bifidobacterium breve DPC 6330 - influence lipid metabolism when ingested with α-linolenic acid (ALA) enriched diet. Four groups of BALB/c mice received ALA enriched diet (3% (w/w)) either alone or in combination with B. breve NCIMB 702258 or B. breve DPC 6330 (109 CFU/day) or unsupplemented control diet for six weeks. The overall n-3 PUFA score was increased in all groups receiving the ALA enriched diet. Hepatic peroxisomal beta oxidation increased following supplementation of the ALA enriched diet with B. breve (P < 0.05) and so the ability of the strains to produce c9t11 conjugated linoleic acid (CLA) was identified in adipose tissue. Furthermore, a strain specific effect of B. breve NCIMB 702258 was found on the endocannabinoid system (ECS). Liver triglycerides (TAG) were reduced following ALA supplementation, compared with unsupplemented controls (P < 0.01) while intervention with B. breve further reduced liver TAG (P < 0.01), compared with the ALA enriched control. These data indicate that the interactions of the gut microbiota with fatty acid metabolism directly affect host health by modulating n-3 PUFA score and the ECS

Effect of resveratrol on plasmatic molecular indicators of brain tissue response to the hypoperfusion/ reperfusion challenge

It is well-documented that endocannabinoids (eCBs) and congeners show a neuroprotective role in several experimental models of brain injury and that changes in eCB levels in peripheral blood cells may reflect the severity of neurological insult. We have previously shown that the preventive administration of dietary natural compounds may increase the plasmatic levels of palmytoylethanolamide (PEA) and oleoylethanolamide (OEA) following the transient bilateral common carotid artery occlusion (BCCAO)-induced brain tissue challenge (1). Resveratrol (RVT), (3,4’, 5-trihidroxystilbene) is a strong natural antioxidant of polyphenolic structure found in grapes and red wine, with many physiological effects, including the prevention of lipid peroxidation in human LDL, inhibition of arachidonic acid metabolism, and platelet activity. RVT has been further shown to protect cerebral tissue and cardiac muscle from tissue damage caused by oxidative stress triggered by reperfusion (2) and has been proposed as a potential neuroprotective agent in treating acute states in focal cerebral ischemia injury (3). In this line, we intend to evaluate whether exogenous administration of RVT prior to induction of BCCAO followed by reperfusion influences the molecular changes occurring in cerebral cortex and plasma, with particular focus on the eCB system. With this aim, cerebral hypoperfusion was produced by a 30 min BCCAO followed by 60 min reperfusion (BCCAO/R). Animals were starved for 12 hours before surgery and 6 hours prior to ischemia RVT (40 mg/kg/0.45 ml of sunflower oil as vehicle) was administered via gavage. Biological samples of plasma, cerebrospinal fluid (CSF), and brain tissue were examined by HPLC, gel zymography, western blot and immunohistochemistry. Data obtained indicate that RVT appears to influence the outcome of BCCAO/R cerebral injury by modulating changes in levels of lipid hydroperoxides, markers of oxidative stress, eCBs and eCB congeners, expression of CB1 and CB2 receptors, peroxisome proliferator-activated receptor- (PPAR) alpha, ciclooxygenase-2 (COX-2) protein levels and enzymatic activity of matrix-metalloproteinase- 9 (MMP-9). Interestingly, changes in brain of some of these parameters, like lipid hydroperoxides, were also found in plasma. Results obtained suggest that exogenous administration of RVT may modulate the brain tissue compensatory or repair mechanisms triggered by the hypoperfusion/reperfusion and support the possible use of this molecule as treatment to prevent the BCCAO/R-induced brain insult. In addition, the finding that changes in plasma mirrored those found in cerebral tissue, opens to the possibility to test whether RSV exerts its positive activities in humans

Involvement of the endocannabinoid system in the physiological response to transient common carotid artery occlusion and reperfusion

Background: The transient global cerebral hypoperfusion/reperfusion achieved by induction of Bilateral Common Carotid Artery Occlusion followed by Reperfusion (BCCAO/R) may trigger a physiological response in an attempt to preserve tissue and function integrity. There are several candidate molecules among which the endocannabinoid system (ECS) and/or peroxisome-proliferator activated receptor-alpha (PPAR-alpha) may play a role in modulating oxidative stress and inflammation. The aims of the present study are to evaluate whether the ECS, the enzyme cyclooxygenase-2 (COX-2) and PPAR-alpha are involved during BCCAO/R in rat brain, and to identify possible markers of the ongoing BCCAO/R-induced challenge in plasma. Methods: Adult Wistar rats underwent BCCAO/R with 30 min hypoperfusion followed by 60 min reperfusion. The frontal and temporal-occipital cortices and plasma were analyzed by high performance liquid chromatography-mass spectrometry (HPLC-MS) to determine concentrations of endocannabinoids (eCBs) and related molecules behaving as ligands of PPAR-alpha, and of oxidative-stress markers such as lipoperoxides, while Western Blot and immunohistochemistry were used to study protein expression of cannabinoid receptors, COX-2 and PPAR-alpha. Unpaired Student's t-test was used to evaluate statistical differences between groups. Results: The acute BCCAO/R procedure is followed by increased brain tissue levels of the eCBs 2-arachidonoylglycerol and anandamide, palmitoylethanolamide, an avid ligand of PPAR-alpha, lipoperoxides, type 1 (CB1) and type 2 (CB2) cannabinoid receptors, and COX-2, and decreased brain tissue concentrations of docosahexaenoic acid (DHA), one of the major targets of lipid peroxidation. In plasma, increased levels of anandamide and lipoperoxides were observed. Conclusions: The BCCAO/R stimulated early molecular changes that can be easily traced in brain tissue and plasma, and that are indicative of the tissue physiological response to the reperfusion-induced oxidative stress and inflammation. The observed variations suggest that the positive modulation of the ECS and the increase of proinflammatory substances are directly correlated events. Increase of plasmatic levels of anandamide and lipoperoxides further suggests that dysregulation of these molecules may be taken as an indicator of an ongoing hypoperfusion/reperfusion challenge

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

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.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.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.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

Acute administration of beta-caryophyllene prevents endocannabinoid system activation during transient common carotid artery occlusion and reperfusion

Background: The transient global cerebral hypoperfusion/reperfusion achieved by induction of Bilateral Common Carotid Artery Occlusion followed by Reperfusion (BCCAO/R) has been shown to stimulate early molecular changes that can be easily traced in brain tissue and plasma, and that are indicative of the tissue physiological response to the reperfusion-induced oxidative stress and inflammation. The aim of the present study is to probe the possibility to prevent the molecular changes induced by the BCCAO/R with dietary natural compounds known to possess anti-inflammatory activity, such as the phytocannabinoid beta-caryophyllene (BCP). Methods: Two groups of adult Wistar rats were used, sham-operated and submitted to BCCAO/R. In both groups, 6 h before surgery, half of the rats were gavage-fed with a single dose of BCP (40 mg/per rat in 300 μl of sunflower oil as vehicle), while the second half were pre-treated with the vehicle alone. HPLC, Western Blot and immunohistochemistry were used to analyze cerebral cortex and plasma. Results: After BCCAO/R, BCP prevented the increase of lipoperoxides occurring in the vehicle-treated rats in both cerebral cortex and plasma. In the frontal cortex, BCP further prevented activation of the endocannabinoid system (ECS), spared the docosahexaenoic acid (DHA), appeared to prevent the increase of cyclooxygenase-2 and increased the peroxisome-proliferator activated receptor-alpha (PPAR-alpha) protein levels, while, in plasma, BCP induced the reduction of arachidonoylethanolamide (AEA) levels as compared to vehicle-treated rats. Conclusions: Collectively, the pre-treatment with BCP, likely acting as agonist for CB2 and PPAR-alpha receptors, modulates in a beneficial way the ECS activation and the lipoperoxidation, taken as indicative of oxidative stress. Furthermore, our results support the evidence that BCP may be used as a dietary supplement to control the physiological response to the hypoperfusion/reperfusion-induced oxidative stress