Role Of Fatty Acids Research Articles

Modulation of adrenocorticotrophin hormone (ACTH)-induced expression of stress-related genes by PUFA in inter-renal cells from European sea bass (Dicentrarchus labrax).

Dietary fatty acids have been shown to exert a clear effect on the stress response, modulating the release of cortisol. The role of fatty acids on the expression of steroidogenic genes has been described in mammals, but little is known in fish. The effect of different fatty acids on the release of cortisol and expression of stress-related genes of European sea bass (Dicentrarchus labrax) head kidney, induced by a pulse of adenocorticotrophin hormone (ACTH), was studied. Tissue was maintained in superfusion with 60 min of incubation with EPA, DHA, arachidonic acid (ARA), linoleic acid or α-linolenic acid (ALA) during 490 min. Cortisol was measured by RIA. The quantification of stress-related genes transcripts was conducted by One-Step TaqMan real-time RT-PCR. There was an effect of the type of fatty acid on the ACTH-induced release of cortisol, values from ALA treatment being elevated within all of the experimental period. The expression of some steroidogenic genes, such as the steroidogenic acute regulatory protein (StAR) and c-fos, were affected by fatty acids, ALA increasing the expression of StAR after 1 h of ACTH stimulation whereas DHA, ARA and ALA increased the expression of c-fos after 20 min. ARA increased expression of the 11β-hydroxylase gene. Expression of heat shock protein 70 (HSP70) was increased in all the experimental treatments except for ARA. Results corroborate previous studies of the effect of different fatty acids on the release of cortisol in marine fish and demonstrate that those effects are mediated by alteration of the expression of steroidogenic genes.

Attempt at elucidation of the role of fatty acids in the resistance of Pinus silvestris L. seeds to infection by damping-off fungi in dependence on the colour of their seed shells

The seed shells of the pine (<i>Pinus silvestris</i> L.) contain in dependence on their colour different amounts of the particular fatty acids. Some of the latter are toxic to the fungi causing damping-off of seedlings. The difference in content of toxic fatty acids between the black and the fallow seed shells may explain the mechanism of their different resistance to infection by damping-off fungi.

Changes of blood fatty acid in women with obesity and type 2 diabetes mellitus

Obesity and type 2 diabetes (DM2) in women are accompanied by atherogenic dyslipidemia, with the activation of lipid peroxidation (LPO), as well as disturbances in the antioxidant defense system (ADS). DM2 due to imbalance in LPO-ADS is accompanied by a high concentration of LPO products, decreased parameters of antioxidant systems and timpaired utilization of glucose by cells. The results obtained in this study suggest an important role of fatty acids and their metabolites in the pathogenesis of obesity and DM2, which should be taken into consideration during design and selection of appropriate preventive and therapeutic measures aimed at prevention or elimination of the violations.

Opportunities and Implications of Pasture-Based Lamb Fattening to Enhance the Long-Chain Fatty Acid Composition in Meat.

Health-conscious consumers following dietary fat recommendations require meat that is low in saturated fat with preferably high levels of long-chain omega-3 fatty acids. This review summarizes the influence of dietary lipids from red meat on human health and examines the potential to enhance lipid composition through pasture-feeding. The role of fatty acids in plant and ruminant metabolism is discussed to highlight the complexity of ruminal digestion when trying to enhance fatty acids in meat. Generally, ruminants that consume pasture diets have been shown to produce a more desirable fatty acid composition than those fed grain and offer potential to be further enhanced by using specific plant species. Elevated polyunsaturated fat content in meat, however, tends to increase susceptibility to oxidation, which influences other meat quality characteristics including shelf-life and color. The use of specific plant species may mitigate these negative effects due to vitamin E or other antioxidants in these plants, which protect polyunsaturated fats from oxidation. When assessing the potential of plants as a natural dietary fat source, consideration must be given to environmental influences on plant fatty acid composition to ensure consistent production of meat products with high nutritive value under a range of management practices. This review also explores the potential impact of climate change on plant fatty acid composition, and the potential implications of this for meat quality.

Lipids and oocyte developmental competence: the role of fatty acids and β-oxidation.

Metabolism and ATP levels within the oocyte and adjacent cumulus cells are associated with quality of oocyte and optimal development of a healthy embryo. Lipid metabolism provides a potent source of energy and its importance during oocyte maturation is being increasingly recognised. The triglyceride and fatty acid composition of ovarian follicular fluid has been characterised for many species and is influenced by nutritional status (i.e. dietary fat, fasting, obesity and season) as well as lactation in cows. Lipid in oocytes is a primarily triglyceride of specific fatty acids which differ by species, stored in distinct droplet organelles that re-localise during oocyte maturation. The presence of lipids, particularly saturated vs unsaturated fatty acids, in in vitro maturation systems affects oocyte lipid content as well as developmental competence. Triglycerides are metabolised by lipases that have been localised to cumulus cells as well as oocytes. Fatty acids generated by lipolysis are further metabolised by β-oxidation in mitochondria for the production of ATP. β-oxidation is induced in cumulus-oocyte complexes (COCs) by the LH surge, and pharmacological inhibition of β-oxidation impairs oocyte maturation and embryo development. Promoting β-oxidation with l-carnitine improves embryo development in many species. Thus, fatty acid metabolism in the mammalian COC is regulated by maternal physiological and in vitro environmental conditions; and is important for oocyte developmental competence.

Impact of chronic heart failure on adipose tissue functional plasticity: a role for fatty acids?

Introduction Chronic heart failure (HF) is a major cause of morbidity and mortality in humans and domestic animals. HF is a systemic condition characterised by chronic inflammation and functional changes in non-cardiovascular tissues; obesity is also associated with low level chronic inflammation, with adipose tissue (AT) exhibiting infiltration of macrophages and alterations in fatty acid (FA) profiles(1).

Differential Effects of Trans and Polyunsaturated Fatty Acids on Ischemia/ Reperfusion Injury and its Associated Cardiovascular Disease States

Fatty acids have an important role in providing energy for sustained contractile activity and viability of the heart. However, considerable evidence now supports a role for fatty acids in the modulation of cardiovascular pathology as well. This may be beneficial or detrimental due to the structural differences in the various fatty acids. Polyunsaturated fatty acids appear to provide important protection to the heart during ischemic reperfusion challenge. Conversely, trans fatty acids are thought to mediate detrimental cardiac effects. Potentially pathological features of ischemic cardiomyocytes may be manifested as qualitative findings in studies of myocardial infarction and atherosclerosis. These general conclusions, however, are complicated by opposing effects that different fatty acids have even within the same group (i.e. n-6 versus n-3 fatty acids within the polyunsaturated fatty acids group, and industrial versus ruminant trans fats). Understanding more about how these fatty acid species alter ischemic myocardial injury is an increasingly attractive area of research. The identification of further targets of fatty acid interactions has great potential to provide valuable information for the modulation of cardiovascular disease.

Peroxisome proliferator-activated receptor-γ stimulates the synthesis of monounsaturated fatty acids in dairy goat mammary epithelial cells via the control of stearoyl-coenzyme A desaturase

In rodents, peroxisome proliferator-activated receptor-γ (PPARG) plays a crucial role in fatty acid (FA) metabolism through regulation of gene expression, including stearoyl-coenzyme A desaturase (SCD), which is the rate-limiting enzyme for the biosynthesis of monounsaturated FA. However, whether or how PPARG regulates the activity of mammary SCD in ruminants is unknown. This study explored the potential role of PPARG isoforms in regulating SCD mRNA expression in lactating goat mammary epithelial cells (GMEC). Using quantitative real-time PCR, we observed a positive correlation between PPARG and SCD expression in the goat mammary gland at peak lactation. Overexpression of both PPARG1 and PPARG2 in GMEC increased markedly the expression of SCD, the concentration of 16:1 and 18:1, and the desaturation indices of 16:1 and 18:1. The PPARG ligand rosiglitazone further increased SCD expression and desaturation indices in GMEC, overexpressing PPARG1 and PPARG2. Incubation with rosiglitazone alone increased the expression of SCD, but did not alter the concentration of 16- to 18-carbon FA or their desaturation indices. The results provide evidence that PPARG regulates the expression and activity of SCD in GMEC. As such, PPARG may contribute to regulation of SCD and monounsaturated FA synthesis during lactation.

Constant pH simulations with the coarse-grained MARTINI model — Application to oleic acid aggregates

Long chain fatty acids are biologically important molecules with complex and pH sensitive aggregation behavior. The carboxylic head group of oleic acid is ionizable, with the pKa shifting to larger values, even above a value of 7, in certain aggregate states. While experiments have determined the macroscopic phase behavior, we have yet to understand the molecular level details for this complex behavior. This level of detail is likely required to fully appreciate the role of fatty acids in biology and for nanoscale biotechnological and industrial applications. Here, we introduce the use of constant pH molecular dynamics (MD) simulations with the coarse-grained MARTINI model and apply the method to oleic acid aggregates and a model lipid bilayer. By running simulations at different constant pH values, we determined titration curves and the resulting pKa for oleic acid in different environments. The coarse-grained model predicts positive pKa shifts, with a shift from 4.8 in water to 6.5 in a small micelle, and 6.6 in a dioleoylphosphatidylcholine (DOPC) bilayer, similar to experimental estimates. The size of the micelles increased as the pH increased, and correlated with the fraction of deprotonated oleic acid. We show this combination of constant pH MD and the coarse-grained MARTINI model can be used to model pH-dependent surfactant phase behavior. This suggests a large number of potential new applications of large-scale MARTINI simulations in other biological systems with ionizable molecules.

Energy metabolism in rat testis after 137Cs incorporation

Testis tissue energy metabolism was investigated in experiments on albino rats by the polarographic method with using of Clark electrode upon 137Cs incorporation. Speed changes are revealed in all metabolic conditions such as oxidation under endogenous and exogenous substrates, uncoupling of oxidative phosphorylation, and decrease share of the fatty acids role in testicular tissue energy production.

A novel sphingolipid-TORC1 pathway critically promotes postembryonic development in Caenorhabditis elegans.

Regulation of animal development in response to nutritional cues is an intensely studied problem related to disease and aging. While extensive studies indicated roles of the Target of Rapamycin (TOR) in sensing certain nutrients for controlling growth and metabolism, the roles of fatty acids and lipids in TOR-involved nutrient/food responses are obscure. Caenorhabditis elegans halts postembryonic growth and development shortly after hatching in response to monomethyl branched-chain fatty acid (mmBCFA) deficiency. Here, we report that an mmBCFA-derived sphingolipid, d17iso-glucosylceramide, is a critical metabolite in regulating growth and development. Further analysis indicated that this lipid function is mediated by TORC1 and antagonized by the NPRL-2/3 complex in the intestine. Strikingly, the essential lipid function is bypassed by activating TORC1 or inhibiting NPRL-2/3. Our findings uncover a novel lipid-TORC1 signaling pathway that coordinates nutrient and metabolic status with growth and development, advancing our understanding of the physiological roles of mmBCFAs, ceramides, and TOR.DOI: http://dx.doi.org/10.7554/eLife.00429.001

The Role of Fatty Acids in the Regulation of Cerebral Vascular Function and Neuroprotection in Ischemia

Cerebral circulation is tightly regulated by vasoactive substances. There is a delicate balance among vasoconstriction and vasodilation factors. During ischemia/stroke, cerebral blood flow autoregulation may be compromised triggering hyperemia (early phase) or hypoperfusion (late phase or post-ischemia) deranging cerebral blood flow that can lead to subsequent neuronal cell death due to blood flow abnormalities. Traditional vasoactive mediators such as nitric oxide and calcitonin gene-related peptide have been well-documented to provide vasodilation and neuroprotection in the ischemic brain. An emerging field is the identification of fatty acids (polyunsaturated or saturated) that can lead to vasodilation possibly causing neuroprotection. This review investigates fatty acids such as palmitic acid methyl ester, α-linolenic acid, and docosahexaenoic acid as novel vasoactive substances that can modulate cerebral blood flow as well as offer neuroprotection after ischemia.

Minor role of fatty acid for mitochondial metabolism during insulin secretion

Minor role of fatty acid for mitochondial metabolism during insulin secretion

Fatty acid correlates of temperament in adolescent boys with attention deficit hyperactivity disorder

Atypical fatty acid metabolism has been reported in attention deficit hyperactivity disorder (ADHD), however, its relationship with temperament in this population is unclear. The current study investigated the association between blood levels of fatty acids implicated in brain structure and function (omega-3, omega-6, omega-9) and personality traits of stability (neuroticism, conscientiousness and agreeableness) and plasticity (extraversion and openness). Twenty right-handed adolescent boys with ADHD completed a self-report NEO-FFI personality questionnaire, and had fatty acid content assessed from red blood using gas chromatography. Pearson's correlations showed no significant associations between omega-3 levels and personality. After correction for multiple comparisons, Adrenic Acid (C22:4n6) was inversely associated with stability. Oleic acid (C18:1n9) was positively associated with plasticity. Results are in line with a role of fatty acids in brain function. They suggest that those fatty acids that are involved in myelination (Adrenic, Oleic) have the strongest associations with temperament in adolescents with ADHD.

Stratum corneum fatty acids: their critical role in preserving barrier integrity during cleansing

Stratum corneum (SC) bilayer lipids, specifically fatty acids, ceramides and cholesterol, contribute to the permeability barrier function of the skin. Normal skin cleansing is associated with damage to the SC lipids because cleanser surfactants, in addition to providing the desired effect of solubilizing and facilitating the removal of sebum and skin soils, have a propensity to disrupt bilayer lipids by extracting endogenous skin lipids or intercalating into the bilayer. Disrupted SC lipids are associated with a variety of pathological skin conditions, as well as with dry skin induced by harsh cleansing. In an attempt to preserve the barrier and mitigate the damage caused by frequent normal cleansing, the incorporation of physiologically relevant lipids into skin cleansers has become common in leading cleansing products. It has been noted that fatty acids are more susceptible to surfactant-induced removal than other lipids (eg, ceramides), an observation that may form the basis for a critically important strategy for replenishing SC lipids. This review will focus on the role of fatty acids in the structure and function of the SC, and the rationale for incorporation of stearic acid into moisturizing body cleansers to minimize their extraction by surfactants and replenish lost fatty acids to promote skin barrier preservation.

Exploring the Role of Fatty Acid on Transcription Factors Regulating Fatty Acid Metabolism with Emphasis on Trans Fatty Acid

Fatty acids are unique macromolecules as they act as biological modulators of transcription factors and regulate their own metabolism by controlling the activity or abundance of transcription factors of fatty acid metabolism either by RNA processing and RNA stability. Peroxisome Proliferator Activated Receptor (PPAR-γ) and Sterol Regulatory Element Binding Protein (SREBP-1c) are transcription factors expressed primarily in adipose tissue. We have studied the relation of fatty acid including trans fatty acid assessed in adipose tissue with the transcription factors. Adipose tissue was collected from 50 healthy subjects undergoing elective abdominal surgery. Fatty acid was assessed in the tissue by gas chromatography. The expressions of PPARγ and SREBP-1c were studied by real time RT-PCR. The expressions of PPARγ and SREBP1c were significantly correlated (r = 0.4 p < 0.005). The trans fatty acid did not show any significant correlation with expression but significant correlation was observed between DHA (Docosahexaenoic acid) and PPARγ expression (r = 0.33 p < 0.03) which remained significant (r = 0.87, p < 0.0001) after being adjusted for BMI and insulin. An upregulation of PPARγ led to decreased levels of SREBP1c. In conclusion, trans fatty acid did not affect the expressions of PPAR-γ and SREB1c in this study.

Serum Fatty Acids and Risk of Cutaneous Melanoma: A Population-Based Case-Control Study

Background. Some observational studies have suggested that excess dietary intake of polyunsaturated fatty acids such as linoleic acid increases cutaneous melanoma risk. We aimed at examining the association between serum fatty acids and melanoma risk by conducting a population-based case-control study in a northern Italy community. Methods. The percentage composition of 12 fatty acids was determined in 51 newly diagnosed melanoma patients and 51 age- and sex-matched population controls by extracting total lipids from serum samples using thin layer and gas chromatography. Conditional logistic regression was used to estimate the relative risk of melanoma associated with tertiles of percentage composition of each fatty acid as well as groupings including saturated, monounsaturated, and polyunsaturated fatty acids. Results. We found a slightly increased melanoma risk for stearic and arachidic acids proportion, with and without adjustment for potential confounders. For an n-3 polyunsaturated fatty acid, docosapentaenoic acid, we found a male-specific direct association with melanoma risk. No other associations emerged for the other saturated, monounsaturated, and polyunsaturated fatty acids, individually or grouped by type. Conclusions. These findings do not suggest a major role of fatty acids, including linoleic acid, on risk of cutaneous melanoma, though their evaluation is limited by the small sample size.

The Role of Fatty Acids and Phospholipase IPLA2 in Mitochondrial ATP-Dependent K+ Channel Activity and Cardioprotection

The Role of Fatty Acids and Phospholipase IPLA2 in Mitochondrial ATP-Dependent K+ Channel Activity and Cardioprotection

High-capacity selective uptake of cholesteryl ester from native LDL during macrophage foam cell formation

Macrophage foam cells are a defining pathologic feature of atherosclerotic lesions. Recent studies have demonstrated that at high concentrations associated with hypercholesterolemia, native LDL induces macrophage lipid accumulation. LDL particles are taken up by macrophages as part of bulk fluid pinocytosis. However, the uptake and metabolism of cholesterol from native LDL during foam cell formation has not been clearly defined. Previous reports have suggested that selective cholesteryl ester (CE) uptake might contribute to cholesterol uptake from LDL independently of particle endocytosis. In this study we demonstrate that the majority of macrophage LDL-derived cholesterol is acquired by selective CE uptake in excess of LDL pinocytosis and degradation. Macrophage selective CE uptake does not saturate at high LDL concentrations and is not down-regulated during cholesterol accumulation. In contrast to CE uptake, macrophages exhibit little selective uptake of free cholesterol (FC) from LDL. Following selective uptake from LDL, CE is rapidly hydrolyzed by a novel chloroquine-sensitive pathway. FC released from LDL-derived CE hydrolysis is largely effluxed from cells but also is subject to ACAT-mediated reesterification. These results indicate that selective CE uptake plays a major role in macrophage metabolism of LDL.

Hepatic mitochondrial dysfunction induced by fatty acids and ethanol

Understanding the key aspects of the pathogenesis of alcoholic fatty liver disease particularly alterations to mitochondrial function remains to be resolved. The role of fatty acids in this regard requires further investigation due to their involvement in fatty liver disease and obesity. This study aimed to characterize the early effects of saturated and unsaturated fatty acids alone on liver mitochondrial function and during concomitant ethanol exposure using isolated liver mitochondria and VA-13 cells (Hep G2 cells that efficiently express alcohol dehydrogenase). Liver mitochondria or VA-13 cells were treated with increasing concentrations of palmitic or arachidonic acid (1 to 160μM) for 24 h with or without 100mM ethanol. The results showed that in isolated liver mitochondria both palmitic and arachidonic acids significantly reduced state 3 respiration in a concentration-dependent manner (P<0.001), implicating their ionophoric activities. Increased ROS production occurred in a dose-dependent manner especially in the presence of rotenone (complex I inhibitor), which was significantly more prominent in arachidonic acid at 80μM (+970%, P<0.001) than palmitic acid (+40%, P<0.01). In VA-13 cells, ethanol alone and both fatty acids (40μM) were able to decrease the mitochondrial membrane potential and cellular ATP levels and increase lipid formation. ROS production was significantly increased with arachidonic acid (+110%, P<0.001) exhibiting a greater effect than palmitic acid (+39%, P<0.05). While in the presence of ethanol, the drop in the mitochondrial membrane potential, cellular ATP levels, and increased lipid formation were further enhanced by both fatty acids, but with greater effect in the case of arachidonic acid, which also correlated with significant cytotoxicity (P<0.001). This study confirms the ability of fatty acids to promote mitochondrial injury in the development of alcoholic fatty liver disease.