PPARs: transcriptional effectors of fatty acids and their derivatives.

Peroxisome proliferator-activated receptors (PPARs) are nuclear hormone receptors that mediate the effects of fatty acids and their derivatives at the transcriptional level. These receptors stimulate transcription after activation by their cognate ligand and binding to the promoter of target genes. In this review, we discuss how fatty acids affect PPAR functions in the cell. We first describe the structural features of the ligand binding domains of PPARs, as defined by crystallographic analyses. We then present the ligand-binding characteristics of each of the three PPARs (alpha, beta/delta, gamma) and relate ligand activation to various cellular processes: (i) fatty acid catabolism and modulation of the inflammatory response for PPARalpha, (ii) embryo implantation, cell proliferation and apoptosis for PPARbeta, and (iii) adipocytic differentiation, monocytic differentiation and cell cycle withdrawal for PPARgamma. Finally, we present possible cross-talk between the PPAR pathway and different endocrine routes within the cell, including the thyroid hormone and retinoid pathways.

Combined effects of endurance training and dietary unsaturated fatty acids on physical performance, fat oxidation and insulin sensitivity.

Endurance training improves exercise performance and insulin sensitivity, and these effects may be in part mediated by an enhanced fat oxidation. Since n-3 and n-9 unsaturated fatty acids may also increase fat oxidation, we hypothesised that a diet enriched in these fatty acids may enhance the effects of endurance training on exercise performance, insulin sensitivity and fat oxidation. To assess this hypothesis, sixteen normal-weight sedentary male subjects were randomly assigned to an isoenergetic diet enriched with fish and olive oils (unsaturated fatty acid group (UFA): 52 % carbohydrates, 34 % fat (12 % SFA, 12 % MUFA, 5 % PUFA), 14 % protein), or a control diet (control group (CON): 62 % carbohydrates, 24 % fat (12 % SFA, 6 % MUFA, 2 % PUFA), 14 % protein) and underwent a 10 d gradual endurance training protocol. Exercise performance was evaluated by measuring VO2max and the time to exhaustion during a cycling exercise at 80 % VO2max; glucose homeostasis was assessed after ingestion of a test meal. Fat oxidation was assessed by indirect calorimetry at rest and during an exercise at 50 % VO2max. Training significantly increased time to exhaustion, but not VO2max, and lowered incremental insulin area under the curve after the test meal, indicating improved insulin sensitivity. Those effects were, however, of similar magnitude in UFA and CON. Fat oxidation tended to increase in UFA, but not in CON. This difference was, however, not significant. It is concluded that a diet enriched with fish- and olive oil does not substantially enhance the effects of a short-term endurance training protocol in healthy young subjects.

Fructose induces synthesis and reduces oxidation of liver fatty acids through ChREBP activation

Introduction and aims. During last few decades, the prevalence of obesity, metabolic syndrome and insulin resistance, among other metabolic disturbances, has raised considerably in many countries worldwide. Environmental factors (diet, physical activity), in tandem with predisposing genetic factors, may be responsible for this trend. Along with an increase in total energy consumption during recent decades, there has also been a shift in the type of nutrients, with an increased consumption of fructose, largely attributable to a greater intake of beverages containing high levels of fructose...

Fructose induces synthesis and reduces oxidation of liver fatty acids through ChREBP activation

Introduction and aims. During last few decades, the prevalence of obesity, metabolic syndrome and insulin resistance, among other metabolic disturbances, has raised considerably in many countries worldwide. Environmental factors (diet, physical activity), in tandem with predisposing genetic factors, may be responsible for this trend. Along with an increase in total energy consumption during recent decades, there has also been a shift in the type of nutrients, with an increased consumption of fructose, largely attributable to a greater intake of beverages containing high levels of fructose...

Use of recovered frying oils in chicken and rabbit feeds: effect on the fatty acid and tocol composition and on the oxidation levels of meat, liver and plasma

The addition of some fat co- and by-products to feeds is usual nowadays; however, the regulations of their use are not always clear and vary between countries. For instance, the use of recycled cooking oils is not allowed in the European Union, but they are used in other countries. However, oils recovered from industrial frying processes could show satisfactory quality for this purpose. Here we studied the effects of including oils recovered from the frying industry in rabbit and chicken feeds (at 30 and 60 g/kg, respectively) on the fatty acid (FA) and tocol (tocopherol + tocotrienol) compositon of meat, liver and plasma, and on their oxidative stability. Three dietary treatments (replicated eight times) were compared: fresh non-used oil (LOX); oil discarded from the frying industry, having a high content of secondary oxidation compounds (HOX); and an intermediate level (MOX) obtained by mixing 50 : 50 of LOX and HOX. The FA composition of oil diets and tissues was assessed by GC, their tocol content by HPLC, the thiobarbituric acid value was used to assess tissue oxidation status, and the ferrous oxidation-xylenol orange method was used to assess the susceptibility of tissues to oxidation. Our results indicate that FA composition of rabbit and chicken meat, liver and plasma was scarcely altered by the addition of recovered frying oils to feed. Differences were encountered in the FA composition between species, which might be attributed mainly to differences in the FA digestion, absorption and metabolism between species, and to some physiological dietary factors (i.e. coprophagy in rabbits that involves fermentation with FA structure modification). The α-tocopherol (αT) content of tissues was reduced in response to the lower αT content in the recovered frying oil. Differences in the content of other tocols were encountered between chickens and rabbits, which might be attributable to the different tocol composition of their feeds, as well as to species differences in the digestion and metabolism of tocols. Tissue oxidation and susceptibility to oxidation were in general low and were not greatly affected by the degree of oxidation of the oil added to the feeds. The relative content of polyunsaturated fatty acids/αT in these types of samples would explain the differences observed between species in the susceptibility of each tissue to oxidation. According to our results, oils recovered from the frying industry could be useful for feed uses.

Use of recovered frying oils in chicken and rabbit feeds: effect on the fatty acid and tocol composition and on the oxidation levels of meat, liver and plasma

The addition of some fat co- and by-products to feeds is usual nowadays; however, the regulations of their use are not always clear and vary between countries. For instance, the use of recycled cooking oils is not allowed in the European Union, but they are used in other countries. However, oils recovered from industrial frying processes could show satisfactory quality for this purpose. Here we studied the effects of including oils recovered from the frying industry in rabbit and chicken feeds (at 30 and 60 g/kg, respectively) on the fatty acid (FA) and tocol (tocopherol1tocotrienol) compositon of meat, liver and plasma, and on their oxidative stability. Three dietary treatments (replicated eight times) were compared: fresh non-used oil (LOX); oil discarded from the frying industry, having a high content of secondary oxidation compounds (HOX); and an intermediate level (MOX) obtained by mixing 50 : 50 of LOX and HOX. The FA composition of oil diets and tissues was assessed by GC, their tocol content by HPLC, the thiobarbituric acid value was used to assess tissue oxidation status, and the ferrous oxidation-xylenol orange method was used to assess the susceptibility of tissues to oxidation. Our results indicate that FA composition of rabbit and chicken meat, liver and plasma was scarcely altered by the addition of recovered frying oils to feed. Differences were encountered in the FA composition between species, which might be attributed mainly to differences in the FA digestion, absorption and metabolism between species, and to some physiological dietary factors (i.e. coprophagy in rabbits that involves fermentation with FA structure modification). The a-tocopherol (aT) content of tissues was reduced in response to the lower aT content in the recovered frying oil. Differences in the content of other tocols were encountered between chickens and rabbits, which might be attributable to the different tocol composition of their feeds, as well as to species differences in the digestion and metabolism of tocols. Tissue oxidation and susceptibility to oxidation were in general low and were not greatly affected by the degree of oxidation of the oil added to the feeds. The relative content of polyunsaturated fatty acids/aT in these types of samples would explain the differences observed between species in the susceptibility of each tissue to oxidation. According to our results, oils recovered from the frying industry could be useful for feed uses.

Kinetics of chronic inflammation in Nile tilapia fed n‑3 and n‑6 essential fatty acids

The objective of this work was to investigate the effect of dietary supplementation with essential fatty acids on the kinetics of macrophage accumulation and giant cell formation in Nile tilapia (Oreochromis niloticus). The supplementation sources were soybean oil (SO, source of omega 6, n‑6) and linseed oil (LO, source of omega 3, n‑3), in the following proportions: 100% SO; 75% SO + 25% LO; 50% SO + 50% LO; 25% SO + 75% LO; and 100% LO (four replicates per treatment). After a feeding period of three months, growth performance was evaluated, and glass coverslips were implanted into the subcutaneous connective tissue of fish, being removed for examination at 2, 4, 6, and 8 days after implantation. Growth performance did not differ between treatments. Fish fed 100% linseed oil diet had the greatest macrophage accumulation and the fastest Langhans cell formation on the sixth day. On the eighth day, Langhans cells were predominant on the coverslips implanted in the fish feed 75 and 100% linseed oil. n‑3 fatty acids may contribute to macrophage recruitment and giant cell formation in fish chronic inflammatory response to foreign body.

Induction of cardiac Angptl4 by dietary fatty acids is mediated by peroxisome proliferator-activated receptor beta/delta and protects against fatty acid-induced oxidative stress.

RATIONALE: Although dietary fatty acids are a major fuel for the heart, little is known about the direct effects of dietary fatty acids on gene regulation in the intact heart. OBJECTIVE: To study the effect of dietary fatty acids on cardiac gene expression and explore the functional consequences. METHODS AND RESULTS: Oral administration of synthetic triglycerides composed of one single fatty acid altered cardiac expression of numerous genes, many of which are involved in the oxidative stress response. The gene most significantly and consistently upregulated by dietary fatty acids encoded Angiopoietin-like protein (Angptl)4, a circulating inhibitor of lipoprotein lipase expressed by cardiomyocytes. Induction of Angptl4 by the fatty acid linolenic acid was specifically abolished in peroxisome proliferator-activated receptor (PPAR)beta/delta(-/-) and not PPARalpha(-/-) mice and was blunted on siRNA-mediated PPARbeta/delta knockdown in cultured cardiomyocytes. Consistent with these data, linolenic acid stimulated binding of PPARbeta/delta but not PPARalpha to the Angptl4 gene. Upregulation of Angptl4 resulted in decreased cardiac uptake of plasma triglyceride-derived fatty acids and decreased fatty acid-induced oxidative stress and lipid peroxidation. In contrast, Angptl4 deletion led to enhanced oxidative stress in the heart, both after an acute oral fat load and after prolonged high fat feeding. CONCLUSIONS: Stimulation of cardiac Angptl4 gene expression by dietary fatty acids and via PPARbeta/delta is part of a feedback mechanism aimed at protecting the heart against lipid overload and consequently fatty acid-induced oxidative stress.

Chemical composition and fatty acid contents in farmed freshwater prawns

The objective of this work was to evaluate the chemical composition and fatty acid contents of Amazonian and giant river prawns. After four-month farming, with the same diet for both species, palmitic and stearic acids were the main saturated fatty acids. Oleic acid was the main monounsatured fatty acid, and the eicosapentaenoic and docosahexaenoic acids were the most abundant polyunsaturated acids. Amazonian prawn has higher levels of protein and polyunsaturated fatty acids than those of the giant river prawn, which shows its potential for aquaculture.

Effect of n-3 fatty acids on markers of brain injury and incidence of sepsis-associated delirium in septic patients.

BACKGROUND: Data regarding immunomodulatory effects of parenteral n-3 fatty acids in sepsis are conflicting. In this study, the effect of administration of parenteral n-3 fatty acids on markers of brain injury, incidence of sepsis-associated delirium, and inflammatory mediators in septic patients was investigated. METHODS: Fifty patients with sepsis were randomized to receive either 2 ml/kg/day of a lipid emulsion containing highly refined fish oil (equivalent to n-3 fatty acids 0.12 mg/kg/day) during 7 days after admission to the intensive care unit or standard treatment. Markers of brain injury and inflammatory mediators were measured on days 1, 2, 3 and 7. Assessment for sepsis-associated delirium was performed daily. The primary outcome was the difference in S-100β from baseline to peak level between both the intervention and the control group, compared by t-test. Changes of all markers over time were explored in both groups, fitting a generalized estimating equations model. RESULTS: Mean difference in change of S-100β from baseline to peak level was 0.34 (95% CI: -0.18-0.85) between the intervention and control group, respectively (P = 0.19). We found no difference in plasma levels of S-100β, neuron-specific enolase, interleukin (IL)-6, IL-8, IL-10, and C-reactive protein between groups over time. Incidence of sepsis-associated delirium was 75% in the intervention and 71% in the control groups (risk difference 4%, 95% CI -24-31%, P = 0.796). CONCLUSION: Administration of n-3 fatty acids did not affect markers of brain injury, incidence of sepsis-associated delirium, and inflammatory mediators in septic patients.

Effect of feed fat by-products with trans fatty acids and heated oil on cholesterol and oxycholesterols in chicken

Chicken is the most widely consumed meat all over the world due to chickens being easy to rear, their fast growth rate and the meat having good nutritional characteristics. The main objective of this paper was to study the effects of dietary fatty by-products in low, medium and high levels of oxidized lipids and trans fatty acids (TFAs) on the contents of cholesterol and oxycholesterols in meat, liver, and plasma of chickens. A palm fatty acid distillate, before and after hydrogenation, and a sunflower-olive oil blend (70/30, v/v) before and after use in a commercial frying process were used in feeding trials after adding 6% of the fats to the feeds. Highly oxidized lipid and TFA feeds significantly increased the contents of cholesterol and oxycholesterols in all tissues of chicken (0.01 < p <= 0.05). The contents of oxycholesterols in chicken meat, liver and plasma obtained from TFA feeding trials varied between 17 and 48 μg/100 g in meat, 19-42 μg/100 g in liver and 105-126 μg/dL in plasma. In contrast, in the oxidized lipid feeding trials, oxycholesterols varied between 13 and 75 μg/100 g in meat, 30-58 μg/100 g in liver and 66-209 μg/dL in plasma. Meat from chickens fed with feeds containing high levels of TFAs or oxidized lipids may contribute to higher ingestion of cholesterol and oxycholesterols by humans.

Characterization of hepatic fatty acids in mice with reduced liver fat by ultra-short echo time (1)H-MRS at 14.1 T in vivo.

Alterations in the hepatic lipid content (HLC) and fatty acid composition are associated with disruptions in whole body metabolism, both in humans and in rodent models, and can be non-invasively assessed by (1)H-MRS in vivo. We used (1)H-MRS to characterize the hepatic fatty-acyl chains of healthy mice and to follow changes caused by streptozotocin (STZ) injection. Using STEAM at 14.1 T with an ultra-short TE of 2.8 ms, confounding effects from T2 relaxation and J-coupling were avoided, allowing for accurate estimations of the contribution of unsaturated (UFA), saturated (SFA), mono-unsaturated (MUFA) and poly-unsaturated (PUFA) fatty-acyl chains, number of double bonds, PU bonds and mean chain length. Compared with in vivo (1) H-MRS, high resolution NMR performed in vitro in hepatic lipid extracts reported longer fatty-acyl chains (18 versus 15 carbons) with a lower contribution from UFA (61 ± 1% versus 80 ± 5%) but a higher number of PU bonds per UFA (1.39 ± 0.03 versus 0.58 ± 0.08), driven by the presence of membrane species in the extracts. STZ injection caused a decrease of HLC (from 1.7 ± 0.3% to 0.7 ± 0.1%), an increase in the contribution of SFA (from 21 ± 2% to 45 ± 6%) and a reduction of the mean length (from 15 to 13 carbons) of cytosolic fatty-acyl chains. In addition, SFAs were also likely to have increased in membrane lipids of STZ-induced diabetic mice, along with a decrease of the mean chain length. These studies show the applicability of (1)H-MRS in vivo to monitor changes in the composition of the hepatic fatty-acyl chains in mice even when they exhibit reduced HLC, pointing to the value of this methodology to evaluate lipid-lowering interventions in the scope of metabolic disorders.

Free Fatty Acids Impair FGF21 Action in HepG2 Cells.

BACKGROUND/AIMS: Fibroblast growth factor 21 (FGF21) is a key mediator of glucose and lipid metabolism. However, the beneficial effects of exogenous FGF21 administration are attenuated in obese animals and humans with elevated levels of circulating free fatty acids (FFA). METHODS: We investigated in vitro how FFA impact FGF21 effects on hepatic lipid metabolism. RESULTS: In the absence of FFA, FGF21 reduced lipogenesis and increased lipid oxidation in HepG2 cells. Inhibition of lipogenesis was associated with a down regulation of SREBP-1c, FAS and SCD1. The lipid-lowering effect was associated with AMPK and ACC phosphorylation, and up regulation of CPT-1α expression. Further, FGF21 treatment reduced TNFα gene expression, suggesting a beneficial action of FGF21 on inflammation. In contrast, the addition of FFA abolished the positive effects of FGF21 on lipid metabolism. CONCLUSION: In the absence of FFA, FGF21 improves lipid metabolism in HepG2 cells and reduces the inflammatory cytokine TNFα. However, under high levels of FFA, FGF21 action on lipid metabolism and TNFα gene expression is impaired. Therefore, FFA impair FGF21 action in HepG2 cells potentially through TNFα.