Palmitic acid (PA) has been for long time negatively depicted for its putative detrimental health effects, shadowing its multiple crucial physiological activities. PA is the most common saturated fatty acid accounting for 20-30% of total fatty acids in the human body and can be provided in the diet or synthesized endogenously via de novo lipogenesis (DNL). PA tissue content seems to be controlled around a well-defined concentration, and changes in its intake do not influence significantly its tissue concentration because the exogenous source is counterbalanced by PA endogenous biosynthesis. Particular physiopathological conditions and nutritional factors may strongly induce DNL, resulting in increased tissue content of PA and disrupted homeostatic control of its tissue concentration. The tight homeostatic control of PA tissue concentration is likely related to its fundamental physiological role to guarantee membrane physical properties but also to consent protein palmitoylation, palmitoylethanolamide (PEA) biosynthesis, and in the lung an efficient surfactant activity. In order to maintain membrane phospholipids (PL) balance may be crucial an optimal intake of PA in a certain ratio with unsaturated fatty acids, especially PUFAs of both n-6 and n-3 families. However, in presence of other factors such as positive energy balance, excessive intake of carbohydrates (in particular mono and disaccharides), and a sedentary lifestyle, the mechanisms to maintain a steady state of PA concentration may be disrupted leading to an over accumulation of tissue PA resulting in dyslipidemia, hyperglycemia, increased ectopic fat accumulation and increased inflammatory tone via toll-like receptor 4. It is therefore likely that the controversial data on the association of dietary PA with detrimental health effects, may be related to an excessive imbalance of dietary PA/PUFA ratio which, in certain physiopathological conditions, and in presence of an enhanced DNL, may further accelerate these deleterious effects.

The biological activities of omega-3 fatty acids (n-3 FAs) have been under extensive study for several decades. However, not much attention has been paid to differences of dietary forms, such as triglycerides (TGs) versus ethyl esters or phospholipids (PLs). New innovative marine raw materials, like krill and fish by-products, present n-3 FAs mainly in the PL form. With their increasing availability, new evidence has emerged on n-3 PL biological activities and differences to n-3 TGs. In this review, we describe the recently discovered nutritional properties of n-3 PLs on different parameters of metabolic syndrome and highlight their different metabolic bioavailability in comparison to other dietary forms of n-3 FAs.

Dietary (n-3) long-chain PUFA [(n-3) LCPUFA] ameliorate several metabolic risk factors for cardiovascular diseases, although the mechanisms of these

Palmitic acid (PA) is ubiquitously present in dietary fat guaranteeing an average intake of about 20 g/d. The relative high requirement and relative content in the human body, which accounts for 20–30% of total fatty acids (FAs), is justified by its relevant nutritional role. In particular physiological conditions, such as in the fetal stage or in the developing brain, the respectively inefficient placental and brain blood–barrier transfer of PA strongly induces its endogenous biosynthesis from glucose via de novo lipogenesis (DNL) to secure a tight homeostatic control of PA tissue concentration required to exert its multiple physiological activities. However, pathophysiological conditions (insulin resistance) are characterized by a sustained DNL in the liver and aimed at preventing the excess accumulation of glucose, which result in increased tissue content of PA and disrupted homeostatic control of its tissue concentration. This leads to an overaccumulation of tissue PA, which results in dyslipidemia, increased ectopic fat accumulation, and inflammatory tone via toll-like receptor 4. Any change in dietary saturated FAs (SFAs) usually reflects a complementary change in polyunsaturated FA (PUFA) intake. Since PUFA particularly n-3 highly PUFA, suppress lipogenic gene expression, their reduction in intake rather than excess of dietary SFA may promote endogenous PA production via DNL. Thereby, the increase in tissue PA and its deleterious consequences from dysregulated DNL can be mistakenly attributed to dietary intake of PA.

Conjugated linoleic acid (CLA) is a naturally occurring fatty acid that is produced by a bio-hydrogenation process in the rumen, and thus is present in dairy products and ruminant meat. In this case the predominant isomer formed is 9cis,11trans. However, CLA includes 28 positional and geometrical isomers, of which only 9cis,11trans and 10trans,12cis have thus far been proven to possess biological activities. Both of these CLA isomers have been shown to undergo elongation and desaturation processes similar to those that occur with linoleic acid, maintaining the conjugated diene structure. There are evidences supporting the hypothesis that CLA metabolism may interfere with eicosanoid formation. Other metabolites with 16 carbon atoms (conjugated 16:2 and 16:3, which are probably derived from peroxisomal β-oxidation of CLA and its metabolites, respectively) have been detected. This suggests an efficient metabolism of CLA and its metabolites in peroxisomes, which might be linked to their capacity to activate peroxisome proliferator-activated receptors.

Background: Omega-3 polyunsaturated fatty acids (ω-3-PUFA) are known to ameliorate several metabolic risk factors for cardiovascular disease, and an association between elevated peripheral levels of endogenous ligands of cannabinoid receptors (endocannabinoids) and the metabolic syndrome has been reported. We investigated the dose-dependent effects of dietary ω-3-PUFA supplementation, given as krill oil (KO), on metabolic parameters in high fat diet (HFD)-fed mice and, in parallel, on the levels, in inguinal and epididymal adipose tissue (AT), liver, gastrocnemius muscle, kidneys and heart, of: 1) the endocannabinoids, anandamide and 2-arachidonoylglycerol (2-AG), 2) two anandamide congeners which activate PPARα but not cannabinoid receptors,N-oleoylethanolamine andN-palmitoylethanolamine, and 3) the direct biosynthetic precursors of these compounds.Methods: Lipids were identified and quantified using liquid chromatography coupled to atmospheric pressure chemical ionization single quadrupole mass spectrometry (LC-APCI-MS) or high resolution ion trap-time of flight mass spectrometry (LC-IT-ToF-MS).Results: Eight-week HFD increased endocannabinoid levels in all tissues except the liver and epididymal AT, and KO reduced anandamide and/or 2-AG levels in all tissues but not in the liver, usually in a dose-dependent manner. Levels of endocannabinoid precursors were also generally down-regulated, indicating that KO affects levels of endocannabinoids in part by reducing the availability of their biosynthetic precursors. Usually smaller effects were found of KO on OEA and PEA levels.Conclusions: Our data suggest that KO may promote therapeutic benefit by reducing endocannabinoid precursor availability and hence endocannabinoid biosynthesis.