The Impact of the hAPP695SW Transgene and Associated Amyloid-β Accumulation on Murine Hippocampal Biochemical Pathways

Background: Alzheimer’s disease (AD) is a neurodegenerative disease characterized by the accumulation of amyloid-β (Aβ) peptide in the brain. Objective: Gain a better insight into alterations in major biochemical pathways underlying AD. Methods: We compared metabolomic profiles of hippocampal tissue of 20-month-old female Tg2576 mice expressing the familial AD-associated hAPP695SW transgene with their 20-month-old wild type female littermates. Results: The hAPP695SW transgene causes overproduction and accumulation of Aβ in the brain. Out of 180 annotated metabolites, 54 metabolites differed (30 higher and 24 lower in Tg2576 versus wild-type hippocampal tissue) and were linked to the amino acid, nucleic acid, glycerophospholipid, ceramide, and fatty acid metabolism. Our results point to 1) heightened metabolic activity as indicated by higher levels of urea, enhanced fatty acid β-oxidation, and lower fatty acid levels; 2) enhanced redox regulation; and 3) an imbalance of neuro-excitatory and neuro-inhibitory metabolites in hippocampal tissue of aged hAPP695SW transgenic mice. Conclusion: Taken together, our results suggest that dysregulation of multiple metabolic pathways associated with a concomitant shift to an excitatory-inhibitory imbalance are contributing mechanisms of AD-related pathology in the Tg2576 mouse.

Effects of Cabbage-Apple Juice Fermented by Lactobacillus plantarum EM on Lipid Profile Improvement and Obesity Amelioration in Rats

This study aimed to investigate the potential of cabbage-apple juice, fermented by Lactobacillus plantarum EM isolated from kimchi, to protect against obesity and dyslipidemia that are induced by a high-fat diet in a rat model. Male rats were fed a modified AIN-93M high-fat diet (HFD), the same diet supplemented with non-fermented cabbage-apple juice, or the same diet supplemented with fermented cabbage-apple juice for eight weeks. In the HFD-fermented cabbage- apple juice administered groups the following parameters decreased: body weight, liver and white fat pad weights, serum triglyceride (TG), total cholesterol (TC), LDL-cholesterol, insulin, glucose and leptin levels, TG levels, while HDL-C and adiponectin levels in serum increased as compared with the HFD group. The HFD-fed rats that were supplemented with fermented cabbage-apple juice exhibited significantly lower fatty acid synthase (FAS), acetyl-CoA carboxylase (ACC), and malic enzyme gene expression levels when compared to the exclusively HFD-fed rats. The anti-obesity and hypolipidemic effects were marginally greater in the fermented juice administered group than in the non-fermented juice administered group. These results suggest that cabbage-apple juice—especially fermented cabbage-apple juice—might have beneficial effects on lipid metabolism dysfunction and obesity-related abnormalities. However, further studies are necessary for analyzing the biochemical regulatory mechanisms of fermented juice for obesity amelioration and lipid metabolic homeostasis.

Fatty acid sensitivity, intake of high-fat foods, gene polymorphism, and body mass

Taste perception is the main biological determinant of food choice. It has thus been hypothesized that fatty acid sensitivity may affect fat intake. The aim of this study was to examine the relationship between fatty acid sensitivity, frequency of consumption of high-fat products, polymorphism of genes encoding proteins involved in fat taste perception, and body mass.421 people aged 20–40 were enrolled in Poznań, Poland. Body composition was measured using a Bod Pod. The frequency of consumption of high-fat foods was analyzed using an application for mobile devices based on the ecological momentary assessment approach. Food intake was assessed with dietary records. Salad dressings with varying concentrations of canola oil (from 2.5% to 40.0%) were used as stimuli to test fatty acid sensitivity. The individuals were then divided into groups with higher and lower fatty acid sensitivity. Lower sensitivity means that individuals were able to distinguish samples when the oil concentration exceeded 20%. Genotyping of rs1761667 (CD36), rs1573611 (FFAR1), and rs17108973 (FFAR4) was performed using TaqMan probes.57% men and 61% women had higher sensitivity to fatty acids. Higher fatty acid sensitivity was associated with the GG genotype of CD36 (OR = 2.05, p < 0.05). People with different taste sensitivity did not differ in their frequency of consumption of high-fat foods or in their macronutrient intake. There was no association between body mass index (BMI) and fatty acid sensitivity, but people with BMI values below 25 more often ate high-fat products with favorable lipid profiles and less often ate meat high-fat products than subjects with BMI values over 25 (p < 0.001 and p < 0.05, respectively). There was no association between CD36 or FFAR4 genotype and fat intake or frequency of consumption of high-fat foods. People with the minor FFAR1 allele ate sweet high-fat products less often than major allele homozygotes (p < 0.05). Moreover, women ate high-fat products with favorable lipid profiles and sweet and savory high-fat products more frequently than men (p < 0.05, p < 0.001, and p < 0.01), but men ate meat high-fat products more frequently than women (p < 0.01).Concluding, fatty acid sensitivity is associated with polymorphism of the CD36 gene. The frequency of consumption of high-fat foods depends on sex, but not on fatty acid sensitivity, BMI, or CD36 variants.The project was financed by a National Science Centre award (decision number grant no. 2014/15/B/NZ9/02134).

Mouse Chow Composition Influences Immune Responses and Food Allergy Development in a Mouse Model

Our diet is known to substantially influence the immune response not only by support of mucosal barriers but also via direct impact on immune cells. Thus, it was of great interest to compare the immunological effect of two mouse chows with substantial differences regarding micro-, macronutrient, lipid and vitamin content on the food allergic response in our previously established mouse model. As the two mouse chows of interest, we used a soy containing feed with lower fatty acid (FA) amount (soy-containing feed) and compared it to a soy free mouse chow (soy-free feed) in an established protocol of oral immunizations with Ovalbumin (OVA) under gastric acid suppression. In the animals receiving soy-containing feed, OVA-specific IgE, IgG1, IgG2a antibody levels were significantly elevated and food allergy was evidenced by a drop of body temperature after oral immunizations. In contrast, mice on soy-free diet had significantly higher levels of IL-10 and were protected from food allergy development. In conclusion, soy-containing feed was auxiliary during sensitizations, while soy-free feed supported oral tolerance development and food allergy prevention.

Different Isolation Methods for Determination of Composition of Volatiles from Nigella damascena L. Seeds

Volatile organic compounds (VOCs) from seeds of Nigella damascena L. were isolated using different techniques. The yield, as well as the qualitative and quantitative composition of the oils, was strongly influenced by the isolation method. In the hydrodistilled essential oil, the major components were the sesquiterpene hydrocarbons β-elemene (59.1%), β-selinene (12.8%) and α-selinene (12.6%). Conventional solvent extraction, followed by hydrodistillation, resulted in a volatile oil with a different composition than that of the hydrodistilled oil. The extracted oils predominantly contained sesquiterpene hydrocarbons, but also methyl anthranilate derivatives. By means of HS-SPME, it was possible to analyze not only sesquiterpenes and anthranilates, but also monoterpenes and the most volatile compounds, for example, the lower fatty acid (butyric, capronic) esters, which determine the characteristic sweet scent of N. damascena seeds. Using all testing methods, 55 compounds were identified, 40 of which are new for N. damascena seed VOCs.

Skeletal muscle lipid metabolism with obesity

The objectives of this study were to 1) examine skeletal muscle fatty acid oxidation in individuals with varying degrees of adiposity and 2) determine the relationship between skeletal muscle fatty acid oxidation and the accumulation of long-chain fatty acyl-CoAs. Muscle was obtained from normal-weight [ n = 8; body mass index (BMI) 23.8 ± 0.58 kg/m2], overweight/obese ( n = 8; BMI 30.2 ± 0.81 kg/m2), and extremely obese ( n = 8; BMI 53.8 ± 3.5 kg/m2) females undergoing abdominal surgery. Skeletal muscle fatty acid oxidation was assessed in intact muscle strips. Long-chain fatty acyl-CoA concentrations were measured in a separate portion of the same muscle tissue in which fatty acid oxidation was determined. Palmitate oxidation was 58 and 83% lower in skeletal muscle from extremely obese (44.9 ± 5.2 nmol · g−1 · h−1) patients compared with normal-weight (71.0 ± 5.0 nmol · g−1 · h−1) and overweight/obese (82.2 ± 8.7 nmol · g−1 · h−1) patients, respectively. Palmitate oxidation was negatively ( R = −0.44, P = 0.003) associated with BMI. Long-chain fatty acyl-CoA content was higher in both the overweight/obese and extremely obese patients compared with normal-weight patients, despite significantly lower fatty acid oxidation only in the extremely obese. No associations were observed between long-chain fatty acyl-CoA content and palmitate oxidation. These data suggest that there is a defect in skeletal muscle fatty acid oxidation with extreme obesity but not overweight/obesity and that the accumulation of intramyocellular long-chain fatty acyl-CoAs is not solely a result of reduced fatty acid oxidation.

Long-chain polyene status of preterm infants with regard to the fatty acid composition of their diet: Comparison between absolute and relative fatty acid levels in plasma and erythrocyte phospholipids

The long-chain polyene (LCP) status of thirty-nine premature infants (birth weight < 1800 g) was evaluated. Twenty-seven infants were fed on an artificial formula, twelve received their own mother's breast milk. Fatty acid compositions of both plasma and erythrocyte (RBC) phospholipids (PL) were determined in umbilical venous blood and in weekly postnatal blood samples until the 28th day of life. Individual fatty acid levels were expressed as absolute quantities (mg fatty acid/I plasma or RBC suspension) and as relative (mg/100 mg total fatty acids) values. The changes with time in the absolute values for 22:6n-3 and 20:4n-6 in plasma were strikingly different from those of the relative values for these fatty acids. In plasma PL the inter-group differences in the absolute postnatal values for 22:6n-3 (P < 0·0005) and 20:4n-6 (P < 0·05) and the relative values for 22:6n-3 (P < 0·02) were significant, with lower fatty acid values in the formula-fed infants. In RBC PL, no significant inter-group differences in the postnatal 22: 6n-3 and 20: 4n-6 values were found. Based on the assumption that it is desirable for formula-fed infants to achieve postnatal plasma LCP values at least comparable with those found in infants fed on human milk, the findings of the present study indicate that both n-3 and n-6 LCP should be added to preterm infant formulas. Moreover, the additional importance of absolute fatty acid levels was demonstrated, although analytical procedures need to be standardized to enable effective comparison of results from different research groups.