Pork Liver Pâté Enriched with Persimmon Coproducts: Effect of In Vitro Gastrointestinal Digestion on Its Fatty Acid and Polyphenol Profile Stability.

Agrofood coproducts are used to enrich meat products to reduce harmful compounds and contribute to fiber and polyphenol enrichment. Pork liver pâtés with added persimmon coproducts (3 and 6%; PR-3 and PR-6, respectively) were developed. Therefore, the aim was to study the effect of their in vitro gastrointestinal digestion on: the free and bound polyphenol profile (HPLC) and their colon-available index; the lipid oxidation (TBARs); and the stability of the fatty acid profile (GC). Furthermore, the effect of lipolysis was investigated using two pancreatins with different lipase activity. Forty-two polyphenols were detected in persimmon flour, which were revealed as a good source of bound polyphenols in pâtés, especially gallic acid (164.3 µg/g d.w. in PR-3 and 631.8 µg/g d.w. in PR-6). After gastrointestinal digestion, the colon-available index in enriched pâté ranged from 88.73 to 195.78%. The different lipase activity in the intestinal phase caused significant differences in bound polyphenols' stability, contributing to increased lipid oxidation. The fatty acids profile in pâté samples was stable, and surprisingly their PUFA content was raised. In conclusion, rich fatty foods, such as pâté, are excellent vehicles to preserve bound polyphenols, which can reach the colon intact and be metabolized by the intestinal microbiome.

Nutritional Status Predicts Fatty Acid Uptake from Fish and Soybean Oil Supplements for Treatment of Cancer-Related Fatigue: Results from a Phase II Nationwide Study.

Cancer-related fatigue is a prevalent and debilitating condition that persists for years into survivorship. Studies evaluating both fish oil supplementation on fatigue and associations between fish oil consumption and fatigue have shown mixed effects; it is unknown what factors contribute to these differential effects. Herein, we investigate whether the nutritional status of cancer survivors was associated with serum omega-3 concentration or change in serum omega-3s throughout a fish oil supplementation study, and then if any of these factors were associated with fatigue. Breast cancer survivors 4-36 months post-treatment with moderate-severe fatigue were randomized to take 6 g fish oil, 6 g soybean oil, or 3 g of each daily for 6 weeks. Baseline nutritional status was calculated using the Controlling Nutritional Status tool (serum albumin, lymphocytes, cholesterol). At baseline and post-intervention, serum fatty acids were quantified and fatigue was assessed using the Multidimensional Fatigue Symptom Inventory. Participants (n = 85) were 61.2 ± 9.7 years old with a body mass index of 31.9 ± 6.7 kg/m2; 69% had a good nutritional score and 31% had light-moderate malnutrition. Those with good nutritional status had greater total serum omega-3s at baseline (p = 0.013) and a greater increase in serum omega-3s with supplementation (p = 0.003). Among those who were supplemented with fish oil, greater increases in serum omega-3s were associated with greater improvements in fatigue. In conclusion, good nutritional status may increase uptake of fatty acid supplements, increasing their ability to improve fatigue.

Mitochondrial Dysfunction is a Key Pathway that Links Saturated Fat Intake to the Development and Progression of NAFLD.

Non-Alcoholic fatty liver disease (NAFLD) is the most common form of liver disease and is characterized by fat accumulation in the liver. Hypercaloric diets generally increase hepatic fat accumulation, whereas hypocaloric diets decrease liver fat content. In addition, there is evidence to suggest that moderate amounts of unsaturated fatty acids seems to be protective for the development of a fatty liver, while consumption of saturated fatty acids (SFA) appears to predispose toward hepatic steatosis. Recent studies highlight a key role for mitochondrial dysfunction in the development and progression of NAFLD. It is proposed that changes in mitochondrial structure and function are key mechanisms by which SFA lead to the development and progression of NAFLD. In this review, it is described how SFA intake is associated with liver steatosis and decreases the efficiency of the respiratory transport chain. This results in the production of reactive oxygen species and damage to nearby structures, eventually leading to inflammation, apoptosis, and scarring of the liver. Furthermore, studies demonstrating that SFA intake affects the composition of mitochondrial membranes are presented, and this process accelerates the progression of NAFLD. It is likely that events are intertwined and reinforce each other, leading to a constant deterioration in health.

Effect of different oleogelators on lipolysis and curcuminoid bioaccessibility upon in vitro digestion of sunflower oil oleogels.

Sunflower oil enriched with curcuminoid compounds (CUs) was gelled by adding 5% (w/w) saturated monoglycerides (MG), rice bran waxes (RW) or a mixture of ß-sitosterol and γ-oryzanol (PS). The resulting oleogels differed for rheological properties and firmness due to the difference in gel network structure. PS oleogel was the firmest sample followed by RW and MG ones. Upon in vitro digestion, fatty acid release as a function of digestion time was greatly affected by oleogel structure: the extent of lipolysis decreased as oleogel strength increased (PS < RW < MG). On the other hand, the nature of the oleogelator affected CUs bioaccessibility, which was lower in oleogels containing crystalline particles (MG and RW). These findings appear interesting in the attempt to develop oleogels able to control lipid digestion as well as to deliver bioactive molecules in food systems.

Adipose tissue protects against sepsis-induced muscle weakness in mice: from lipolysis to ketones.

BACKGROUND: ICU-acquired weakness is a debilitating consequence of prolonged critical illness that is associated with poor outcome. Recently, premorbid obesity has been shown to protect against such illness-induced muscle wasting and weakness. Here, we hypothesized that this protection was due to increased lipid and ketone availability. METHODS: In a centrally catheterized, fluid-resuscitated, antibiotic-treated mouse model of prolonged sepsis, we compared markers of lipolysis and fatty acid oxidation in lean and obese septic mice (n = 117). Next, we compared markers of muscle wasting and weakness in septic obese wild-type and adipose tissue-specific ATGL knockout (AAKO) mice (n = 73), in lean septic mice receiving either intravenous infusion of lipids or standard parenteral nutrition (PN) (n = 70), and in lean septic mice receiving standard PN supplemented with either the ketone body 3-hydroxybutyrate or isocaloric glucose (n = 49). RESULTS: Obese septic mice had more pronounced lipolysis (p ≤ 0.05), peripheral fatty acid oxidation (p ≤ 0.05), and ketogenesis (p ≤ 0.05) than lean mice. Blocking lipolysis in obese septic mice caused severely reduced muscle mass (32% loss vs. 15% in wild-type, p < 0.001) and specific maximal muscle force (59% loss vs. 0% in wild-type; p < 0.001). In contrast, intravenous infusion of lipids in lean septic mice maintained specific maximal muscle force up to healthy control levels (p = 0.6), whereas this was reduced with 28% in septic mice receiving standard PN (p = 0.006). Muscle mass was evenly reduced with 29% in both lean septic groups (p < 0.001). Lipid administration enhanced fatty acid oxidation (p ≤ 0.05) and ketogenesis (p < 0.001), but caused unfavorable liver steatosis (p = 0.01) and a deranged lipid profile (p ≤ 0.01). Supplementation of standard PN with 3-hydroxybutyrate also attenuated specific maximal muscle force up to healthy control levels (p = 0.1), but loss of muscle mass could not be prevented (25% loss in both septic groups; p < 0.001). Importantly, this intervention improved muscle regeneration markers (p ≤ 0.05) without the unfavorable side effects seen with lipid infusion. CONCLUSIONS: Obesity-induced muscle protection during sepsis is partly mediated by elevated mobilization and metabolism of endogenous fatty acids. Furthermore, increased availability of ketone bodies, either through ketogenesis or through parenteral infusion, appears to protect against sepsis-induced muscle weakness also in the lean.

Complementary low-density lipoprotein-cholesterol lowering and pharmacokinetics of adding bempedoic acid (ETC-1002) to high-dose atorvastatin background therapy in hypercholesterolemic patients: A randomized placebo-controlled trial.

BACKGROUND: Bempedoic acid is an oral, once-daily, first-in-class medication being developed to treat hypercholesterolemia. OBJECTIVE: The aim of the study was to assess the low-density lipoprotein cholesterol (LDL-C)-lowering efficacy of bempedoic acid added to stable high-intensity atorvastatin background therapy and multiple-dose plasma pharmacokinetics of atorvastatin alone and combined with steady-state bempedoic acid. METHODS: This was a phase 2 study in patients with hypercholesterolemia (NCT02659397). Patients received once-daily open-label atorvastatin 80 mg for 4 weeks then were randomized 2:1 at baseline to receive double-blind bempedoic acid 180 mg (n = 45) or placebo (n = 23) plus open-label atorvastatin 80 mg for 4 weeks. Efficacy was assessed 4 weeks after randomization. Atorvastatin and metabolites' steady-state levels were analyzed before first dosing with bempedoic acid and after 2 weeks of treatment. RESULTS: The 4-week stabilization phase with 80 mg atorvastatin resulted in approximately 40% lowering of LDL-C values from screening. The placebo-adjusted least squares mean lowering of LDL-C from baseline to Day 29 with bempedoic acid was 22% (P = .003). Placebo-adjusted reductions from baseline with bempedoic acid also were significant for total cholesterol (-10%; P = .014), non-high-density lipoprotein cholesterol (-13%; P = .015), apolipoprotein B (-15%; P = .004), and high-sensitivity C-reactive protein (-44%; P = .002). Point estimates of bempedoic acid effects on steady-state atorvastatin and ortho-hydroxy atorvastatin area under the curve were <30% and not clinically meaningful. CONCLUSIONS: Bempedoic acid 180 mg added to stable high-dose atorvastatin therapy effectively lowers LDL-C in patients with hypercholesterolemia without causing clinically important increases in atorvastatin exposure.

Comparison of the Incorporation of DHA in Circulatory and Neural Tissue When Provided as Triacylglycerol (TAG), Monoacylglycerol (MAG) or Phospholipids (PL) Provides New Insight into Fatty Acid Bioavailability.

Phospholipids (PL) or partial acylglycerols such as sn-1(3)-monoacylglycerol (MAG) are potent dietary carriers of long-chain polyunsaturated fatty acids (LC-PUFA) and have been reported to provide superior bioavailability when compared to conventional triacylglycerol (TAG). The main objective of the present study was to compare the incorporation of docosahexaenoic acid (DHA) in plasma, erythrocytes, retina and brain tissues in adult rats when provided as PL (PL-DHA) and MAG (MAG-DHA). Conventional dietary DHA oil containing TAG (TAG-DHA) as well as control chow diet were used to evaluate the potency of the two alternative DHA carriers over a 60-day feeding period. Fatty acid profiles were determined in erythrocytes and plasma lipids at time 0, 7, 14, 28, 35 and 49 days of the experimental period and in retina, cortex, hypothalamus, and hippocampus at 60 days. The assessment of the longitudinal evolution of DHA in erythrocyte and plasma lipids suggest that PL-DHA and MAG-DHA are efficient carriers of dietary DHA when compared to conventional DHA oil (TAG-DHA). Under these experimental conditions, both PL-DHA and MAG-DHA led to higher incorporations of DHA erythrocytes lipids compared to TAG-DHA group. After 60 days of supplementation, statistically significant increase in DHA level incorporated in neural tissues analyzed were observed in the DHA groups compared with the control. The mechanism explaining hypothetically the difference observed in circulatory lipids is discussed.

Polyphenols and Their Interactions With Other Dietary Compounds: Implications for Human Health.

Regular and optimal intake of polyphenols associates with numerous health-promoting effects. Bioavailability and activity of polyphenols depend on foods' structure and interactions with other food constituents, especially proteins, lipids, and carbohydrates. Polyphenols-proteins interactions can result in various biological effects, such as sense of astringency. So far, polyphenols interactions with food lipids have not been of special importance, except in case of plant oils. Polyphenols-carbohydrates interactions can influence the organoleptic properties, while interactions with dietary fibers are particularly significant. Polyphenols can decrease the synthesis of fats and fatty acids in the liver, or delay their absorption in intestines. Also, polyphenols can slow down digestion of carbohydrates, through the inhibition of digestive enzymes or modulation of glucose uptake. Both animal and plant proteins have low impact on the bioavailability of polyphenols, but some in vitro studies reported that milk proteins could enhance intestinal absorption of polyphenols from tea. Dietary fats may alter the passage of polyphenols through gastrointestinal tract and impact absorption of more hydrophobic polyphenols in particular. While some studies reported that associations with carbohydrates could decrease bioavailability of polyphenols, the others showed the opposite effects. Macronutrients can be used for encapsulation of polyphenols, which can increase their bioavailability and ensure controlled and targeted release. Polyphenols' interactions in the body include their incorporation in cell membranes which causes changes in fatty acid profile and impacts membrane-bound transporters and enzymes. Finally, gut microbiota plays essential role in metabolism of both polyphenols and macronutrients and thus can have great impact on their interactions.

Effect of three edible oils on the intestinal absorption of caffeic acid: An in vivo and in vitro study.

Polyphenolic antioxidants are mainly absorbed through passive paracellular permeation regulated by tight junctions. Some fatty acids are known to modulate tight junctions. Fatty acids resulting from the digestion of edible oils may improve the absorption of polyphenolic antioxidants. Therefore, we explored the effect of three edible oils on the intestinal absorption of caffeic acid. Rats were fed with soybean oil and caffeic acid dissolved in distilled water. Caffeic acid contents in the plasma collected up to 1 hr were quantified. The experiment was repeated with coconut oil and olive oil. Component fatty acids of the oils were individually tested in vitro for their effect on permeability of caffeic acid using Caco-2 cell monolayers. Highest absorption of caffeic acid was observed in animals fed with coconut oil. In vitro transport percentages of caffeic acid in 2.5 mmol/L solutions of fatty acids were 22.01±0.12 (lauric), 15.30 ± 0.25 (myristic acid), 13.59 ± 0.35 (linoleic acid), 3.70 ± 0.09 (oleic acid) and 0.10-2.0 (all other fatty acids). Lauric acid and myristic acid are the two major fatty acids present in coconut oil. Therefore, these fatty acids may contribute to the higher absorption of caffeic acid in the presence of coconut oil.

Whole Milk Increases Intestinal ANGPTL4 Expression and Excretion of Fatty Acids through Feces and Urine.

The angiopoietin-like 4 (ANGPLT4) protein is involved in lipid metabolism and is known to inhibit lipoprotein lipase in the bloodstream. We investigated the effect of milk on intestinal ANGPTL4 and the metabolic profile of growing pigs and the effect of free fatty acids (FFAs) on ANGPTL4 in ex vivo and in vitro assays. Feeding pigs whole milk increased intestinal ANGPTL4 mRNA and increased fecal excretion of long-chain FFA compared to the control group fed soybean oil (n = 9). Furthermore, FFAs (C4-C8) induced ANGPTL4 gene expression in porcine intestinal tissue mounted in Ussing chambers and ANGPTL4 protein secretion to both the apical and basolateral sides of intestinal Caco-2 cells on permeable membranes. Altogether, these results support an ANGPTL4-induced secretion of fecal FFAs. Urinary levels of FFAs (C4-C12), 3-hydroxyadipic acid, and suberic acid were also increased by milk consumption, indicating higher energy expenditure compared to the control group.

Skin-mimetic chromatography for prediction of human percutaneous absorption of biologically active compounds occurring in medicinal plant extracts.

The main aim of this study was to predict quantitatively human percutaneous absorption of chosen compounds commonly occurring in plants which can be used as medicinal extracts in the drug and beauty industries. The most important human percutaneous descriptors, i.e. logKp (logarithm of the water/skin partition coefficient) and logJmax (logarithm of the maximum flux of solutes penetrating the skin), of fatty acids and polyphenols were determined using both in vitro and in silico methods. For in vitro determination of human percutaneous absorption, micellar liquid chromatography based on hexadecyltrimethylammonium bromide, sodium dodecyl sulfate and polyoxyethylene (23) lauryl ether (Brij35) was used. Human percutaneous absorption was characterized by entirely new QSAR/QRAR models based on retention, lipophilic, steric and electronic data as well as on the linear free energy relationship parameters. Many different correlations between human skin absorption and different physicochemical parameters were performed, e.g. the in silico estimated logKp value was correlated with the retention parameter logkw (logarithm of the retention factor extrapolated to pure water) from the systems imitating a cutaneous environment (R2 = 0.92). Moreover, the influence of lipophilicity on percutaneous absorption was examined. The obtained correlation was excellent (R2 = 0.95).

Pharmacokinetic Studies of Ganoderic Acids from the Lingzhi or Reishi Medicinal Mushroom, Ganoderma lucidum (Agaricomycetes), by LC-MS/MS.

Ganoderma lucidum is a famous medicinal mushroom that has been widely used in clinical practice and as a dietary supplementa. The triterpenoid ganoderic acids are the main constituents of G. lucidum. To determine the pharmacokinetic characteristics of ganoderic acids, we developed and validated a sensitive and selective liquid chromatography-tandem mass spectrometry method to determine simultaneously the concentration of 4 representative ganoderic acids in rat plasma after oral administration of the extract from G. lucidum. Because of the similarity of their chemical structures, the 4 components exhibited similar pharmacokinetic behaviors in some aspects. However, some of the pharmacokinetic parameters and the reabsorption peaks in the plasma concentration-time curves of ganoderic acids B and E after oral administration of the extract were different from those of ganoderic acids D and A because of the metabolic transformation among the ganoderic acids. These results increase our knowledge about the use of G. lucidum.

Dietary α-linolenic acid-rich flaxseed oil prevents against alcoholic hepatic steatosis via ameliorating lipid homeostasis at adipose tissue-liver axis in mice.

Low levels of n-3 polyunsaturated fatty acids (PUFAs) in serum and liver tissue biopsies are the common characteristics in patients with alcoholic liver disease. The α-linolenic acid (ALA) is a plant-derived n-3 PUFA and is rich in flaxseed oil. However, the impact of ALA on alcoholic fatty liver is largely unknown. In this study, we assessed the potential protective effects of ALA-rich flaxseed oil (FO) on ethanol-induced hepatic steatosis and observed that dietary FO supplementation effectively attenuated the ethanol-induced hepatic lipid accumulation in mice. Ethanol exposure stimulated adipose lipolysis but reduced fatty acid/lipid uptake, which were normalized by FO. Our investigations into the corresponding mechanisms demonstrated that the ameliorating effect of FO might be associated with the lower endoplasmic reticulum stress and normalized lipid metabolism in adipose tissue. In the liver, alcohol exposure stimulated hepatic fatty acid uptake and triglyceride synthesis, which were attenuated by FO. Additionally, dietary FO upregulated plasma adiponectin concentration, hepatic adiponectin receptor 2 expression, and the activation of hepatic adenosine monophosphate-activated protein kinase. Collectively, dietary FO protects against alcoholic hepatic steatosis by improving lipid homeostasis at the adipose tissue-liver axis, suggesting that dietary ALA-rich flaxseed oil might be a promising approach for prevention of alcoholic fatty liver.

The mechanism of lowering cholesterol absorption by calcium studied by using an in vitro digestion model.

Studies in humans show that a calcium-enriched diet leads to lower cholesterol in blood serum. This phenomenon is usually explained in the literature with a reduced cholesterol absorption in the small intestine. Our study aims to clarify the effect of calcium on the solubilisation of cholesterol and fatty acid in the dietary mixed micelles (DMM), viz. on the bioaccessibility of these lipophilic substances in the gut. We use an in vitro digestion model which mimics very closely the intestinal pH-profile and the composition of the intestinal fluids. We quantified the effects of Ca(2+) concentration on the lipid solubilization for fats and oils with different saturated/unsaturated fatty acid (FA) contents. We found that the increase of calcium significantly decreases the solubilization of cholesterol, FA and MG. Most importantly, we observe a clear positive correlation between the amounts of solubilized cholesterol, on one side, and solubilized free fatty acids and monoglycerides, on the other side. The main conclusion is that Ca(2+) ions strongly affect the bioaccessibility of both cholesterol and saturated FA. Therefore, calcium may decrease the serum cholesterol via two complementary mechanisms: (1) fatty acid precipitation by calcium ions reduces the solubilisation capacity of the DMM, thus decreasing the levels of solubilised (bioaccessible) cholesterol; (2) the observed strong decrease of the bioaccessible saturated FA, in its own turn, may suppress the cholesterol synthesis in the liver.

Hepatic fatty acid profile of rats fed a triheptanoin-based ketogenic diet / Perfil de ácidos grasos de hígados de ratones alimentados con una dieta cetogénica basada en triheptanoína

Objective: the aim of this study was to evaluate the influence of consumption of a ketogenic diet supplemented with triheptanoin, a medium-chain anaplerotic triacylglycerol, on the liver fatty acid profile of Wistar rats. Methods: three groups of male Wistar rats (n=10) were submitted to an AIN-93 control diet, a triheptanoin-based ketogenic diet, or a soybean oil-based ketogenic diet for 60 days. Excised livers were subjected to lipid extraction and methylation to obtain fatty acids methyl esters, which were subjected to gas chromatography-mass spectrometry. Results and discussion: compared to the rats fed the control diet, those fed ketogenic diets showed a significant reduction in the concentrations of 9-hexadecenoic and 9-octadecenoic acids, whereas those fed triheptanoin showed increased levels of octadecanoic acid. Conclusion: changes in the liver fatty acid profiles of the rats fed a triheptanoin-based or a soybean oil-based ketogenic diet did not seem to be related to the dietary fat source, but rather to the characteristics of the ketogenic diets themselves (AU)

Objetivo: el objetivo de este estudio fue evaluar la influencia del consumo de una dieta cetogénica complementada con triheptanoína, un triacilglicerol de cadena media y anaplerótico, en el perfil de ácidos grasos del hígado de ratones Wistar. Métodos: tres grupos de ratones Wistar machos (n=10) fueron sometidos durante 60 días a una dieta AIN-93 de control, una dieta cetogénica basada en triheptanoína o una dieta cetogénica a base de aceite de soja. Los hígados fueron escindidos y sometidos a extracción de lípidos y metilación para obtener los ésteres metílicos de ácidos grasos, que se sometieron a cromatografía de gas-espectrometría de masa. Resultados y discusión: en comparación con los ratones alimentados con la dieta de control, los de ambas dietas cetogénicas mostraron una reducción significativa en las concentraciones de los ácidos grasos 9-hexadecenoico y 9-octadecenoico, mientras que los alimentados con triheptanoína mostraron niveles de ácido octadecenoico aumentados. Conclusión: los cambios en los perfiles de ácidos grasos del hígado de los ratones alimentados con dietas cetogénicas no están relacionados con la fuente de grasa de la dieta (triheptanoína o aceite de soja), sino más bien con la concentración total de lípidos (AU)

Assessment of myocardial metabolic disorder associated with mediastinal radiotherapy for esophageal cancer -a pilot study.

BACKGROUND: To evaluate the dose-effect relations for myocardial metabolic disorders after mediastinal radiotherapy (RT) by performing iodine-123 ß-methyl-iodophenyl pentadecanoic acid (I-123 BMIPP) scintigraphy. METHODS: Between 2011 and 2012, we performed I-123 BMIPP scintigraphy for patients with esophageal cancer before and six months after curative mediastinal RT. Single photon emission computed tomography (SPECT) images of pre-RT and post-RT were registered into RT dose distributions. The myocardium was contoured, and the regional RT dose was calculated. Normalization is required to compare pre- and post-RT SPECT images because the uptake pattern is changed due to the breathing level. Normalization was applied on the mean of SPECT counts in regions of the myocardium receiving less than 5 Gy. Relative values in each dose region (interval of 5 Gy) were calculated on the basis of this normalization for each patient. The reduction in the percent of relative values was calculated. RESULTS: Five patients were enrolled in this study. None of the patients had a past history of cardiac disease. The left ventricle was partially involved in RT fields in all patients. The patients received RT with median total doses of 60-66 Gy for the primary tumor and metastatic lymph nodes. Concomitant chemotherapy consisting of cisplatin or nedaplatin and 5-fluorouracil with RT was performed in 4 patients. All patients had reduced uptake corresponding to RT fields. Dose-effect relations for reduced uptake tended to be observed at 6 months after RT with mean decreases of 8.96% in regions at 10-15 Gy, 12.6% in regions at 20-25 Gy, 15.6% in regions at 30-35 Gy, 19.0% in regions at 40-45 Gy and 16.0% in regions at 50-55 Gy. CONCLUSIONS: Dose-effect relations for myocardial metabolic disorders tended to be observed. We may need to make an effort to reduce high-dose mediastinal RT to the myocardium in RT planning.

Incorporation of exogenous fatty acids protects Enterococcus faecalis from membrane-damaging agents.

Enterococcus faecalis is a commensal bacterium of the mammalian intestine that can persist in soil and aquatic systems and can be a nosocomial pathogen to humans. It employs multiple stress adaptation strategies in order to survive such a wide range of environments. Within this study, we sought to elucidate whether membrane fatty acid composition changes are an important component for stress adaptation. We noted that E. faecalis OG1RF was capable of changing its membrane composition depending upon growth phase and temperature. The organism also readily incorporated fatty acids from bile, serum, and medium supplemented with individual fatty acids, often dramatically changing the membrane composition such that a single fatty acid was predominant. Growth in either low levels of bile or specific individual fatty acids was found to protect the organism from membrane challenges such as high bile exposure. In particular, we observed that when grown in low levels of bile, serum, or the host-derived fatty acids oleic acid and linoleic acid, E. faecalis was better able to survive the antibiotic daptomycin. Interestingly, the degree of membrane saturation did not appear to be important for protection from the stressors examined here; instead, it appears that a specific fatty acid or combination of fatty acids is critical for stress resistance.

Selenium promotes adipogenic determination and differentiation of chicken embryonic fibroblasts with regulation of genes involved in fatty acid uptake, triacylglycerol synthesis and lipolysis.

Selenium (Se) has been utilized in the differentiation of primary pig and rat preadipocytes, indicating that it may have proadipogenic potential; however, some studies have also demonstrated that Se has antiadipogenic activity. In this study, chicken embryonic fibroblasts (CEFs) were used to investigate the role of Se in adipogenesis in vitro and in ovo. Se supplementation increased lipid droplet accumulation and inhibited proliferation of cultured CEFs isolated from 6-day-old embryos dose-dependently. This suggests that Se may play a role in cell cycle inhibition, thereby promoting the differentiation of fibroblasts to adipocytes. Se did not stimulate adipogenic differentiation of CEFs isolated from 9- to 12-day-old embryos, implying a permissive stage of adipogenic determination by Se at earlier embryonic ages. Microarray analysis comparing control and Se treatments on CEFs from 6-day-old embryos and confirmatory analysis by quantitative real-time polymerase chain reaction revealed that genes involved in adipocyte determination and differentiation, fatty acid uptake and triacylglycerol synthesis were up-regulated. In addition, up-regulation of an anti-lipolytic G0/G1 switch gene 2 and down-regulation of a prolipolytic monoglyceride lipase may lead to inhibition of lipolysis by Se. Both osteogenic and myogenic genes were down-regulated, and several genes related to oxidative stress response during adipogenesis were up-regulated. In ovo injection of Se at embryonic day 8 increased adipose tissue mass by 30% and caused adipocyte hypertrophy in 17-day-old chicken embryos, further supporting the proadipogenic role of Se during the embryonic development of chickens. These results suggest that Se plays a significant role in several mechanisms related to adipogenesis.

La suplementación de larga duración con atenolol convierte la insaturación de las membranas mitocondriales de músculo esquelético y de corazón de ratón en la característica de mamíferos de supervivencia diez veces mayor. Efectos sobre la longevidad media y máxima / Long-life supplementation with atenolol converts the heart and skeletal muscle unsaturation of mitochondrial membranes of mice into those of ten fold longer-lived mammals. Effects on mean and maximum longevity

Se estudia por primera vez el efecto a largo plazo del atenolol en el agua de bebida durante toda la vida (3,3 años) de un mamífero (128 ratones C57BL/6 macho-SPF). Observamos cambios beneficiosos relacionados con el envejecimiento: descenso en el grado de insaturación de las membranas mitocondriales y del ácido graso 22:6n-3, un incremento del ácido oleico, y descenso de la oxidación, glicoxidación y lipoxidación de proteínas y daño oxidativo al ADNmt en mitocondrias de corazón y músculo esquelético. Sin embargo, detectamos un efecto secundario del fármaco sólo en animales viejos que coincide con meta-análisis recientes en pacientes humanos (AU)

The long-term effects of atenolol in drinking water throughout the whole lifespan (3.3 years) of a mammal (128 C57BL/6 male mice-SPF) were studied for the first time. We observed beneficial aging-related changes: decreases in the degree of unsaturation of mitochondrial membranes and of the 22:6n-3 fatty acid, an increase in oleic acid, as well as decreases in protein oxidation, glycoxidation and lipoxidation and oxidative damage in mtDNA in heart and skeletal muscle mitochondria. However, a secondary effect of the drug only in old animals was detected that agrees with recent meta-analyses in human patients (AU)

Comparison of the effects of pelargonic acid vanillylamide and capsaicin on human vanilloid receptors.

Pelargonic acid vanillylamide is like capsaicin a natural capsaicinoid from chili peppers and commonly used in food additives to create a hot sensation, even in self-defense pepper sprays and as an alternative to capsaicin in medical products for topical treatment of pain. Although the chemical structures of both compounds are similar, preclinical data suggest that capsaicin is the more potent compound. We therefore performed voltage-clamp recordings using cells transfected with the human vanilloid receptor TRPV1 in order to assess the responses of pelargonic acid vanillylamide and capsaicin at the receptor level. We provide evidence that at the molecular target TRPV1, the concentration-response curves, kinetics of current activation, as well as inhibition by the competitive antagonist capsazepine were not significantly different between the two capsaicinoids. We suggest that the different effects of the two capsaicinoids observed in previous studies may rather be due to different physicochemical or pharmacokinetic properties than to different pharmacological profiles at the receptor level.