Attività dello squalene durante l'autossidazione di acidi grassi poliinsaturi

In this paper we have investigated the activity of squalene during the autoxidation of four different polyunsaturated fatty acids: linoleic, linolenic, arachidonic and docosahexaenoic acids. Our results show that squalene exerts a weak but significant antioxidant activity, and that squalene hydroperoxide, the product derived from squalene oxidation, does not possess prooxidant activity. The protection exerted by squalene is higher versus linolenic, arachidonic and docosahexaenoic acids than linoleic acid. Squalene antioxidant activity is related to its double bond system since its saturated form, squalane, does not exert any inhibitory activity. Therefore, in our experimental conditions, squalene does not act as a hydrogen atoms donor such as α-tocopherol

High-density lipoprotein contribute to G0-G1/S transition in Swiss NIH/3T3 fibroblasts

High density lipoproteins (HDLs) play a crucial role in removing excess cholesterol from peripheral tissues. Although their concentration is lower during conditions of high cell growth rate (cancer and infections), their involvement during cell proliferation is not known. To this aim, we investigated the replicative cycles in synchronized Swiss 3T3 fibroblasts in different experimental conditions: i) contact-inhibited fibroblasts re-entering cell cycle after dilution; ii) scratch-wound assay; iii) serum deprived cells induced to re-enter G1 by FCS, HDL or PDGF. Analyses were performed during each cell cycle up to quiescence. Cholesterol synthesis increased remarkably during the replicative cycles, decreasing only after cells reached confluence. In contrast, cholesteryl ester (CE) synthesis and content were high at 24h after dilution and then decreased steeply in the successive cycles. Flow cytometry analysis of DiO-HDL, as well as radiolabeled HDL pulse, demonstrated a significant uptake of CE-HDL in 24h. DiI-HDL uptake, lipid droplets (LDs) and SR-BI immunostaining and expression followed the same trend. Addition of HDL or PDGF partially restore the proliferation rate and significantly increase SR-BI and pAKT expression in serum-deprived cells. In conclusion, cell transition from G0 to G1/S requires CE-HDL uptake, leading to CE-HDL/SR-BI pathway activation and CEs increase into LDs

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

Modificazioni dei livelli di acido arachidonico e vitamina A in relazione alla attività anticancerogena attribuita all'apporto alimentare di burro naturalmente arricchito in acido linoleico a dieni coniugati (CLA)

Considerable attention has recently been directed to the naturally occurring trace fatty acid conjugated linoleic acid (CLA), based on its dual ability to act both as a preventive and therapeutic agent in a number of rodent and human tumor model systems. CLA, which is synthesized by rumen bacteria, is found in meat and dairy products, and is of particular interest since it is effective at low levels in the diet. Our research interest is to explore whether the mechanism of the anticarcinogenic activity of CLA may be reconductible to its metabolism and influence on tissue lipid metabolism. CLA is a polyunsaturated fatty acid (PUFA) with two singular properties: 1) Its metabolism is alike that of linoleic acid and thus competes with the latter for the elongation and desaturation enzyme systems, leading on one hand to a decreased generation of eicosatrienoic and arachidonic acids for eicosanoid synthesis, and on the other to a replacement of the natural substrates with CLA metabolites known to inhibit the cyclooxigenase (COX) and lipooxygenase (LPOX) pathways; and 2) It increases the retinol content of different tissues, an effect that may be due to β-oxidation of CLA by peroxisomes with consequent activation of peroxisome proliferator activated receptor a (PPARα). The effects of CLA on eicosanoid synthesis may be the key factor of a common mechanism underlying its pleiotropic activities, and our current working hypothesis is that this factor along with tissue retinol increase, mediate the anticarcinogenic action of CLA

Mitochondrial physiology

As the knowledge base and importance of mitochondrial physiology to evolution, health and disease expands, the necessity for harmonizing the terminology concerning mitochondrial respiratory states and rates has become increasingly apparent. The chemiosmotic theory establishes the mechanism of energy transformation and coupling in oxidative phosphorylation. The unifying concept of the protonmotive force provides the framework for developing a consistent theoretical foundation of mitochondrial physiology and bioenergetics. We follow the latest SI guidelines and those of the International Union of Pure and Applied Chemistry (IUPAC) on terminology in physical chemistry, extended by considerations of open systems and thermodynamics of irreversible processes. The concept-driven constructive terminology incorporates the meaning of each quantity and aligns concepts and symbols with the nomenclature of classical bioenergetics. We endeavour to provide a balanced view of mitochondrial respiratory control and a critical discussion on reporting data of mitochondrial respiration in terms of metabolic flows and fluxes. Uniform standards for evaluation of respiratory states and rates will ultimately contribute to reproducibility between laboratories and thus support the development of data repositories of mitochondrial respiratory function in species, tissues, and cells. Clarity of concept and consistency of nomenclature facilitate effective transdisciplinary communication, education, and ultimately further discovery

Mitochondrial physiology

As the knowledge base and importance of mitochondrial physiology to evolution, health and disease expands, the necessity for harmonizing the terminology concerning mitochondrial respiratory states and rates has become increasingly apparent. The chemiosmotic theory establishes the mechanism of energy transformation and coupling in oxidative phosphorylation. The unifying concept of the protonmotive force provides the framework for developing a consistent theoretical foundation of mitochondrial physiology and bioenergetics. We follow the latest SI guidelines and those of the International Union of Pure and Applied Chemistry (IUPAC) on terminology in physical chemistry, extended by considerations of open systems and thermodynamics of irreversible processes. The concept-driven constructive terminology incorporates the meaning of each quantity and aligns concepts and symbols with the nomenclature of classical bioenergetics. We endeavour to provide a balanced view of mitochondrial respiratory control and a critical discussion on reporting data of mitochondrial respiration in terms of metabolic flows and fluxes. Uniform standards for evaluation of respiratory states and rates will ultimately contribute to reproducibility between laboratories and thus support the development of data repositories of mitochondrial respiratory function in species, tissues, and cells. Clarity of concept and consistency of nomenclature facilitate effective transdisciplinary communication, education, and ultimately further discovery

Fatty Acid Metabolism and Derived-Mediators Distinctive of PPAR-α Activation in Obese Subjects Post Bariatric Surgery

Bariatric surger (BS) is characterized by lipid metabolic changes as a response to the massive release of non-esterified fatty acids (NEFA) from adipose depots. The study aimed at evaluating changes in polyunsaturated fatty acids (PUFA) metabolism and biosynthesis of the lipid mediators N-acylethanolamines (NAE), as indices of nuclear peroxisome proliferator-activated receptor (PPAR)-α activation. The observational study was performed on 35 subjects (27 female, 8 male) with obesity, undergoing bariatric surgery. We assessed plasma FA and NAE profiles by LC-MS/MS, clinical parameters and anthropometric measures before and 1 and 6 months after bariatric surgery. One month after bariatric surgery, as body weight and clinical parameters improved significantly, we found higher plasma levels of N-oleoylethanolamine, arachidonic and a 22:6-n3/20:5-n3 ratio as evidence of PPAR-α activation. These changes corresponded to higher circulating levels of NEFA and a steep reduction of the fat mass. After 6 months 22:6-n3/20:5-n3 remained elevated and fat mass was further reduced. Our data suggest that the massive release of NEFA from adipose tissue at 1-Post, possibly by inducing PPAR-α, may enhance FA metabolism contributing to fat depot reduction and improved metabolic parameters in the early stage. However, PUFA metabolic changes favor n6 PUFA biosynthesis, requiring a nutritional strategy aimed at reducing the n6/n3 PUFA ratio