Increased nitrate intake from beetroot juice over 4 weeks affects nitrate metabolism, but not vascular function or blood pressure in older adults with hypertension.

The decline in vascular function and increase in blood pressure with aging contribute to an increased cardiovascular disease risk. In this randomized placebo-controlled crossover study, we evaluated whether previously reported cardiovascular benefits of plant-derived inorganic nitrate via nitric oxide (NO) translate into improved vascular function and blood pressure-lowering in 15 men and women (age range: 56-71 years) with treated hypertension. We investigated the effects of a single ∼400 mg-dose at 3 hours post-ingestion (3H POST) and the daily consumption of 2 × âˆ¼400 mg of nitrate through nitrate-rich compared with nitrate-depleted (placebo) beetroot juice over 4 weeks (4WK POST). Measurements included nitrate and nitrite in plasma and saliva; endothelial-dependent and -independent forearm blood flow (FBF) responses to acetylcholine (FBFACh) and glyceryltrinitrate (FBFGTN); and clinic-, home- and 24-hour ambulatory blood pressure. Compared to placebo, plasma and salivary nitrate and nitrite increased at 3H and 4WK POST following nitrate treatment (P < 0.01), suggesting a functioning nitrate-nitrite-NO pathway in the participants of this study. There were no differences between treatments in FBFACh and FBFGTN-area under the curve (AUC) ratios [AUC ratios after (3H POST, 4WK POST) compared with before (PRE) the intervention], or 24-hour ambulatory blood pressure or home blood pressure measures (P > 0.05). These findings do not support the hypothesis that an increased intake of dietary nitrate exerts sustained beneficial effects on FBF or blood pressure in hypertensive older adults, providing important information on the efficacy of nitrate-based interventions for healthy vascular aging. This study was registered under ClinicialTrials.gov (NCT04584372).

Association between vitamin D status, physical performance, sex, and lifestyle factors: a cross-sectional study of community-dwelling Kosovar adults aged 40 years and older.

PURPOSE: Vitamin D status and its association with age-related decline in physical performance and strength have already been highlighted in various ways, but data on the situation in developing countries are scarce. This study aimed to investigate vitamin D status, its association with muscle mass and function, and other potential determinants such as age, sex, lifestyle factors (physical activity, dietary behavior), self-perceived health status, medication intake, education and financial situation in adults from Kosovo. METHODS: This cross-sectional study included 297 participants (54.5% women), aged ≥ 40 years. Serum 25-hydroxyvitamin D (25(OH)D) concentration, hand grip strength and physical performance tests, body composition, vitamin D dietary intake and knowledge were assessed. The interaction between serum 25(OH)D status, lifestyle factors and muscle traits was investigated. RESULTS: Vitamin D deficiency (< 50 nmol/L) was observed in 47.5% of the total population, of whom 14.7% of them were severely deficient (< 30 nmol/L). No associations were found between 25(OH)D concentration and age. Daily dietary intake of vitamin D was low (1.89 ± 0.67 µg) and 87.6% of individuals did not take vitamin D supplements. However, vitamin D supplementation was the only variable that added statistical significance (p < 0.05) to the prediction of vitamin D status (3.8%). On the other hand, age, medication intake and vitamin D level contributed significantly to the overall regression model, explaining 24.9% of the 30-s chair stand performance as an indicator of lower-body strength endurance. CONCLUSION: Vitamin D deficiency is highly prevalent among community-dwelling adults in Kosovo and low serum 25(OH)D has been associated with low muscle strength. This implies an urgent need for the development of comprehensive prevention strategies, focusing on pharmacological (supplementation) but also on non-pharmacological strategies such as education, food fortification or lifestyle advices.

The influence of vitamin D supplementation and strength training on health biomarkers and chromosomal damage in community-dwelling older adults.

Older adults lack of proper physical activity which is often accompanied by vitamin D deficiency. Those factors are known to contribute to health issues in the later years of life. The main goal of this intervention study was to investigate the effect of different vitamin D supplementation strategies for 4 weeks solely or combined with a 10-week strength training program on chromosomal stability in peripheral blood mononuclear cells in community-dwelling older people. One hundred women and men (65-85 years) received either vitamin D3 daily (800 IU), a monthly dose (50.000 IU) or placebo for 17 weeks. All groups received 400 mg calcium daily. The fitness status of the study participants was measured using the 30- second chair stand test, the handgrip strength test and the 6-min walk test. The cytokinesis block micronucleus cytome (CBMN) assay was applied to analyze chromosomal anomalies, including cytotoxic and genotoxic parameters. Changes in antioxidant markers were measured in plasma. Walking distance and chair stand performance improved significantly. Increased levels of the parameters of the CBMN assay were detected for all intervention groups at study end. At baseline micronuclei (MNi) frequency correlated significantly with BMI in both sexes (females: r = 0.369, p = 0.034; males: r = 0.265, p = 0.035), but not with vitamin D serum levels. In females, body fat (r = 0.372, p < 0.001) and functional parameter using the 30-s chair stand test (r = 0.311, p = 0.002) correlated significantly with MNi frequency. Interestingly, not vitamin D supplementation but 10 weeks of resistance training increased MNi frequency indicating elevated chromosomal instability and also adverse effects on antioxidant markers including glutathione and FRAP were detected in the group of community-dwelling older adults.

Resistance training with or without nutritional supplementation showed no influence on muscle thickness in old-institutionalized adults: a secondary analysis of the Vienna Active Ageing Study.

BACKGROUND: Resistance training and protein supplementation are recommended strategies to combat sarcopenia. AIM: Quantification of muscle thickness (MT) by musculoskeletal ultrasound is a promising method to follow changes in skeletal muscles. The aim of this study was to investigate the effect of six months of resistance training with or without nutritional supplementation on MT of M. quadriceps in institutionalized old adults. DESIGN: This is a prospective, randomized, multi-arm parallel and controlled intervention study. SETTING: This study was conducted in five different retirement care facilities. POPULATION: Institutionalized individuals (mean age 82.6±6.2 years) were randomly assigned to an elastic band resistance training (N.=41), training with nutritional supplementation (N.=36) or control group (N.=40). METHODS: Health status and handgrip strength were investigated at baseline. MT of all parts of M. quadriceps of the left leg was assessed using musculoskeletal ultrasound at baseline and after six months. Linear regression models adjusted for age, BMI and sex were calculated to investigate the influence of baseline characteristics on MT. Multivariable regression analyses were performed for investigation of study intervention on MT. Follow-up examinations were performed after 12 and 18 months. RESULTS: Handgrip strength of both hands was significantly correlated with MT of M. vastus lateralis. Moreover, the sum of regularly taken medication was significantly correlated to MT of all parts of quadriceps. Six months of training or nutritional supplementation was not able to alter MT. However, participants with lower baseline MT values or a higher number of diseases and medications at baseline showed significant higher increases in MT after intervention. CONCLUSIONS: Resistance training using elastic bands with or without nutritional supplementation did not alter MT of M. quadriceps of old institutionalized individuals. However, baseline values and health status had a significant influence on the training effect. CLINICAL REHABILITATION IMPACT: As old individuals are very heterogenic according to their health and muscle status; further studies might focus on individualizing training regimes with particular emphasize on accompanied diseases and medications of this population.

Sexual dimorphism: increased sterol excretion leads to hypocholesterolaemia in female hyperbilirubinaemic Gunn rats.

Circulating bilirubin is associated with reduced serum cholesterol concentrations in humans and in hyperbilirubinaemic Gunn rats. However, mechanisms contributing to hypocholesterolaemia remain unknown. Therefore, this study aimed to investigate cholesterol synthesis, transport and excretion in mutant Gunn rats. Adult Gunn and control rats were assessed for daily faecal sterol excretion using metabolic cages, and water was supplemented with [1-13 C]-acetate to determine cholesterol synthesis. Bile was collected to measure biliary lipid secretion. Serum and liver were collected for biochemical analysis and for gene/protein expression using RT-qPCR and western blot, respectively. Additionally, serum was collected and analysed from juvenile rats. A significant interaction of sex, age and phenotype on circulating lipids was found with adult female Gunn rats reporting significantly lower cholesterol and phospholipids. Female Gunn rats also demonstrated elevated cholesterol synthesis, greater biliary lipid secretion and increased total faecal cholesterol and bile acid excretion. Furthermore, they possessed increased hepatic low-density lipoprotein (LDL) receptor and SREBP2 expression. In contrast, there were no changes to sterol metabolism in adult male Gunn rats. This is the first study to demonstrate elevated faecal sterol excretion in female hyperbilirubinaemic Gunn rats. Increased sterol excretion creates a negative intestinal sterol balance that is compensated for by increased cholesterol synthesis and LDL receptor expression. Therefore, reduced circulating cholesterol is potentially caused by increased hepatic uptake via the LDL receptor. Future studies are required to further evaluate the sexual dimorphism of this response and whether similar findings occur in females with benign unconjugated hyperbilirubinaemia (Gilbert's syndrome). KEY POINTS: Female adult hyperbilirubinaemic (Gunn) rats demonstrated lower circulating cholesterol, corroborating human studies that report a negative association between bilirubin and cholesterol concentrations. Furthermore, female Gunn rats had elevated sterol excretion creating a negative intestinal sterol balance that was compensated for by elevated cholesterol synthesis and increased hepatic low-density lipoprotein (LDL) receptor expression. Therefore, elevated LDL receptor expression potentially leads to reduced circulating cholesterol levels in female Gunn rats providing an explanation for the hypocholesterolaemia observed in humans with elevated bilirubin levels. This study also reports a novel interaction of sex with the hyperbilirubinaemic phenotype on sterol metabolism because changes were only reported in females and not in male Gunn rats. Future studies are required to further evaluate the sexual dimorphism of this response and whether similar findings occur in females with benign unconjugated hyperbilirubinaemia (Gilbert's syndrome).

Nutritional supplementation alters associations between one-carbon metabolites and cardiometabolic risk profiles in older adults: a secondary analysis of the Vienna Active Ageing Study.

PURPOSE: Cardiovascular diseases and cognitive decline, predominant in ageing populations, share common features of dysregulated one-carbon (1C) and cardiometabolic homeostasis. However, few studies have addressed the impact of multifaceted lifestyle interventions in older adults that combine both nutritional supplementation and resistance training on the co-regulation of 1C metabolites and cardiometabolic markers. METHODS: 95 institutionalised older adults (83 ± 6 years, 88.4% female) were randomised to receive resistance training with or without nutritional supplementation (Fortifit), or cognitive training (control for socialisation) for 6 months. Fasting plasma 1C metabolite concentrations, analysed by liquid chromatography coupled with mass spectrometry, and cardiometabolic parameters were measured at baseline and the 3- and 6-month follow-ups. RESULTS: Regardless of the intervention group, choline was elevated after 3 months, while cysteine and methionine remained elevated after 6 months (mixed model time effects, p < 0.05). Elevated dimethylglycine and lower betaine concentrations were correlated with an unfavourable cardiometabolic profile at baseline (spearman correlations, p < 0.05). However, increasing choline and dimethylglycine concentrations were associated with improvements in lipid metabolism in those receiving supplementation (regression model interaction, p < 0.05). CONCLUSION: Choline metabolites, including choline, betaine and dimethylglycine, were central to the co-regulation of 1C metabolism and cardiometabolic health in older adults. Metabolites that indicate upregulated betaine-dependent homocysteine remethylation were elevated in those with the greatest cardiometabolic risk at baseline, but associated with improvements in lipid parameters following resistance training with nutritional supplementation. The relevance of how 1C metabolite status might be optimised to protect against cardiometabolic dysregulation requires further attention.

Association between Polymorphisms in Vitamin D Pathway-Related Genes, Vitamin D Status, Muscle Mass and Function: A Systematic Review.

An association between vitamin D level and muscle-related traits has been frequently reported. Vitamin D level is dependent on various factors such as sunlight exposure and nutrition. But also on genetic factors. We, therefore, hypothesize that single nucleotide polymorphisms (SNPs) within the vitamin D pathway-related genes could contribute to muscle mass and function via an impact on vitamin D level. However, the integration of studies investigating these issues is still missing. Therefore, this review aimed to systematically identify and summarize the available evidence on the association between SNPs within vitamin D pathway-related genes and vitamin D status as well as various muscle traits in healthy adults. The review has been registered on PROSPERO and was conducted following PRISMA guidelines. In total, 77 studies investigating 497 SNPs in 13 different genes were included, with significant associations being reported for 59 different SNPs. Variations in GC, CYP2R1, VDR, and CYP24A1 genes were reported most frequently, whereby especially SNPs in the GC (rs2282679, rs4588, rs1155563, rs7041) and CYP2R1 genes (rs10741657, rs10766197, rs2060793) were confirmed to be associated with vitamin D level in more than 50% of the respective studies. Various muscle traits have been investigated only in relation to four different vitamin D receptor (VDR) polymorphisms (rs7975232, rs2228570, rs1544410, and rs731236). Interestingly, all of them showed only very low confirmation rates (6-17% of the studies). In conclusion, this systematic review presents one of the most comprehensive updates of the association of SNPs in vitamin D pathway-related genes with vitamin D status and muscle traits in healthy adults. It might be used for selecting candidate SNPs for further studies, but also for personalized strategies in identifying individuals at risk for vitamin D deficiency and eventually for determining a potential response to vitamin D supplementation.

Effects of Vitamin D3 Supplementation and Resistance Training on 25-Hydroxyvitamin D Status and Functional Performance of Older Adults: A Randomized Placebo-Controlled Trial.

Vitamin D status is associated with muscle strength and performance in older adults. To examine the additive effects of vitamin D3 supplementation during resistance training, 100 seniors (65-85 years) participated in a 16-week intervention. Besides a daily dose of 400 mg of calcium, participants received either 800 IU vitamin D3 per day (VDD), 50,000 IU vitamin D3 per month (VDM) or nothing (CON). After the initial loading phase of four weeks, all groups started a 10-week resistance training program. Assessments of 25-hydroxyvitamin D (25(OH)D) status, muscle strength endurance (30-s chair stand and arm curl tests), aerobic capacity (6-min walk test) and functional mobility (gait speed and timed up and go test) were undertaken at baseline, after four weeks and at the end of the study. 25(OH)D status significantly improved in VDD and VDM, but not in CON (time x group: p = 0.021), as 15.2% of CON, 40.0% of VDD and 61.1% of VDM reached vitamin D sufficiency (>30 ng/mL; p = 0.004). Chair stand test, arm curl test, 6-min walk test, gait speed and timed up and go test improved over the whole intervention period (p < 0.05), however only chair stand and arm curl test were selectively affected by resistance training (p < 0.001). Neither muscle strength endurance, nor functional mobility or aerobic capacity were modulated by vitamin D supplementation. Therefore, the mere amelioration of 25(OH)D status of older adults does not lead to an additive effect on muscular performance during RT.

Effects of dietary fatty acids on the social life of male Guinea pigs from adolescence to adulthood.

Dietary intake of polyunsaturated fatty acids (PUFAs) or saturated fatty acids (SFAs) differently modulates neurophysiological and behavioral functions in response to altered hypothalamic-pituitary-adrenal (HPA)-axis activity and an individual's development. In this context, an individual's social environment, including social interactions and social hierarchies, is closely related to hormone concentrations and possibly interacts with dietary fatty acid effects. We investigated if dietary supplementation with walnut oil (high in PUFAs) and coconut fat (high in SFAs), compared to a control group, affects body mass gain, cortisol and testosterone concentrations, plasma fatty acids, and social behavior in male domestic guinea pigs from adolescence to adulthood. For analyses of cortisol and testosterone concentrations, social interactions were included as covariates in order to consider effects of social behavior on hormone concentrations. Our results revealed that SFAs increased escalated conflicts like fights and stimulated cortisol and testosterone concentrations, which limited body mass gain and first-year survival. PUFAs did not remarkably affect social behavior and hormone concentrations, but enabled the strongest body mass gain, which probably resulted from an energetic advantage. Neither sociopositive nor agonistic behaviors explained age-specific differences in hormone concentrations between groups. However, a high number of subdominant individuals and lower testosterone concentrations were related to increased cortisol concentrations in adult PUFA males. Our findings demonstrate the importance of dietary fatty acids regarding behavioral and endocrine developmental processes and adaptations to the social environment by modulating HPA-axis function and body homeostasis.

Chromosomal stability in buccal cells was linked to age but not affected by exercise and nutrients - Vienna Active Ageing Study (VAAS), a randomized controlled trial.

The purpose of this study was to investigate the effect of six months strength training with or without supplementing protein and vitamins, on chromosomal integrity of buccal cells in institutionalized elderly. One hundred seventeen women and men (65-98 years) performed either resistance training (RT), RT combined with a nutritional supplement (RTS) or cognitive training (CT) twice per week for six months. Participants' fitness was measured using the 6 min walking, the chair rise, and the handgrip strength test. Genotoxicity and cytotoxicity parameters were investigated with the Buccal Micronucleus Cytome (BMcyt) assay. Six minutes walking and chair rise performance improved significantly, however, no changes of the parameters of the BMcyt were detected. Age and micronuclei (MN) frequency correlated significantly, for both women (r = 0.597, p = 0.000) and men (r = 0.508, p = 0.000). Squared regressions revealed a significant increase in the MN frequency of buccal cells with age (R2 = 0.466, p = 0.000). Interestingly and contrary to what was shown in blood lymphocytes, chromosomal damage in buccal cells increases until very old age, which might qualify them as a valid biomarker for aging. Unexpectedly, in this group of institutionalized elderly, resistance training using elastic bands had no effect on chromosomal damage in buccal cells.

Fat Soluble Vitamins in Institutionalized Elderly and the Effect of Exercise, Nutrition and Cognitive Training on Their Status-The Vienna Active Aging Study (VAAS): A Randomized Controlled Trial.

BACKGROUND: Institutionalized elderly are at higher risk for micronutrient deficiency. In particular, fat soluble micronutrients, which additionally have antioxidative function, are of interest. The purpose of this secondary investigation of the Vienna Active Ageing Study was to assess and evaluate the plasma status of retinol, alpha- and gamma-tocopherol, alpha- and beta-carotene, lutein, zeaxanthin, beta-cryptoxanthin, and lycopene, as well as vitamin D (25(OH)D) in a cohort of institutionalized elderly. We further determined the effect of six months strength training with or without supplementing (antioxidant) vitamins and protein on the plasma status of these ten micronutrients. METHODS: Three groups (n = 117, age = 83.1 ± 6.1 years)-resistance training (RT), RT combined with protein and vitamin supplementation (RTS), or cognitive training (CT)-performed two guided training sessions per week for six months. Micronutrients were measured with High Performance Liquid Chromatography (HPLC) at baseline and after 6 months of intervention. Physical fitness was assessed by the 6-min-walking, the 30-s chair rise, isokinetic dynamometry, and the handgrip strength tests. RESULTS: At baseline, the plasma status of retinol was satisfactory, for alpha-tocopherol, beta-carotene, and 25(OH)D, the percentage of individuals with an insufficient status was 33%, 73% and 61%/81% (when using 50 nmol/L or 75 nmol/L as threshold levels for 25(OH)D), respectively. Plasma analyses were supported by intake data. Six months of elastic band resistance training with or without protein-vitamin supplementation had no biological impact on the status of fat soluble micronutrients. Even for vitamin D, which was part of the nutritional supplement (additional 20 µg/d), the plasma status did not increase significantly, however it contributed to a lower percentage of elderly below the threshold levels of 50/75 nmol/L (49%/74%). CONCLUSIONS: The findings of the study lead to the strong recommendation for regular physical activity and increased consumption of plant-based foods in institutionalized elderly. When supported by blood analysis, supplementing micronutrients in a moderate range should also be considered.

Saliva cortisol responses to altered plasma PUFA patterns in guinea pigs.

PUFA modulate hypothalamic-pituitary-adrenal (HPA) axis activity and cortisol concentrations and therefore affect physiological stress responses and the regulation of energy balance in the short- and long-term. Especially dietary intake of n-3 PUFA and a lowered n-6:n-3 ratio are highly encouraged due to beneficial and diminishing effects on basal cortisol secretions. However, the time of such effects to occur and how plasma PUFA patterns affect cortisol concentrations in the short-term was rarely investigated. In order to address this, we supplemented forty male and forty female guinea pigs with diets high in the essential PUFA α-linolenic acid (ALA, 18 : 3n-3) and linoleic acid (LA, 18 : 2n-6) for 20 d. Saliva cortisol concentrations in relation to altering plasma PUFA patterns during this time span were analysed in a repeated measurement design both during basal conditions (individual housing) in 5-d intervals and during stressful social confrontations. We detected very fast plasma PUFA accumulation rates, corresponding to the major dietary PUFA, which resulted in plasma PUFA plateau phases after 10 d. ALA negatively and LA positively affected saliva cortisol concentrations throughout the study. A positive effect of the plasma n-6:n-3 ratio on saliva cortisol concentrations was detected during peak plasma PUFA accumulations and social confrontations, while no effects were detected in relation to plasma PUFA plateau phases. These results suggest that the plasma n-6:n-3 ratio diminishes HPA axis activity during altered physiological conditions only and highlights the importance of altering plasma PUFA patterns for HPA axis functions and the control of energy balance and physiological stress.

Counteraction of Oxidative Stress by Vitamin E Affects Epigenetic Regulation by Increasing Global Methylation and Gene Expression of MLH1 and DNMT1 Dose Dependently in Caco-2 Cells.

Obesity- or diabetes-induced oxidative stress is discussed as a major risk factor for DNA damage. Vitamin E and many polyphenols exhibit antioxidative activities with consequences on epigenetic regulation of inflammation and DNA repair. The present study investigated the counteraction of oxidative stress by vitamin E in the colorectal cancer cell line Caco-2 under normal (1 g/l) and high (4.5 g/l) glucose cell culture condition. Malondialdehyde (MDA) as a surrogate marker of lipid peroxidation and reactive oxygen species (ROS) was analyzed. Gene expression and promoter methylation of the DNA repair gene MutL homolog 1 (MLH1) and the DNA methyltransferase 1 (DNMT1) as well as global methylation by LINE-1 were investigated. Results revealed a dose-dependent counteracting effect of vitamin E on H2O2-induced oxidative stress. Thereby, 10 µM vitamin E proved to be more efficient than did 50 µM in reducing MDA. Further, an induction of MLH1 and DNMT1 gene expression was noticed, accompanied by an increase in global methylation. Whether LINE-1 hypomethylation is a cause or effect of oxidative stress is still unclear. In conclusion, supplementation of exogenous antioxidants like vitamin E in vitro exhibits beneficial effects concerning oxidative stress as well as epigenetic regulation involved in DNA repair.

Age and the effect of exercise, nutrition and cognitive training on oxidative stress - The Vienna Active Aging Study (VAAS), a randomized controlled trial.

The purpose of this study was to investigated the effect of age - over or under life-expectancy (LE) - on six months resistance training alone or combined with a nutritional supplement, and cognitive training by analyzing markers for oxidative stress and antioxidant defense in institutionalized elderly, living in Vienna. Three groups (n = 117, age = 83.1 ±â€¯6.1 years) - resistance training (RT), RT combined with protein and vitamin supplementation (RTS) or cognitive training (CT) - performed two guided training sessions per week for six months. Oxidative stress, antioxidant defense and DNA strand breaks were analyzed and transformed into an "antioxidant factor" to compare the total effect of the intervention. Physical fitness was assessed by the 6-min-walking, the chair-rise and the handgrip strength tests. We observed significant negative baseline correlations between 8-oxo-7.8-dihydroguanosine and handgrip strength (r = -0.350, p = 0.001), and between high sensitive troponin-T and the 6-min-walking test (r = -0.210, p = 0.035). RT and RTS groups, showed significant improvements in physical performance. Over LE, subjects of the RT group demonstrated a significant greater response in the "antioxidant factor" compared to RTS and CT (RT vs. RTS p = 0.033, RT vs. CT p = 0.028), whereas no difference was observed between the intervention groups under LE. Six months of elastic band resistance training lead to improvements in antioxidant defense, DNA stability and oxidative damage, summarized in the "antioxidant factor", however mainly in subjects over their statistical LE. Consuming a supplement containing antioxidants might inhibit optimal cellular response to exercise. The study was approved by the ethics committee of the City of Vienna (EK-11-151-0811) and registered at ClinicalTrials.gov, NCT01775111.

Dietary fatty acids sex-specifically modulate guinea pig postnatal development via cortisol concentrations.

Early ontogenetic periods and postnatal maturation in organisms are sex-specifically sensitive to hypothalamic-pituitary-adrenal (HPA)-axis activities, related glucocorticoid secretions, and their effects on energy balance and homeostasis. Dietary polyunsaturated (PUFAs) and saturated (SFAs) fatty acids potentially play a major role in this context because PUFAs positively affect HPA-axis functions and a shift towards SFAs may impair body homeostasis. Here we show that dietary PUFAs positively affect postnatal body mass gain and diminish negative glucocorticoid-effects on structural growth rates in male guinea pigs. In contrast, SFAs increased glucocorticoid concentrations, which positively affected testes size and testosterone concentrations in males, but limited their body mass gain and first year survival rate. No distinct diet-related effects were detectable on female growth rates. These results highlight the importance of PUFAs in balancing body homeostasis during male's juvenile development, which clearly derived from a sex-specific energetic advantage of dietary PUFA intakes compared to SFAs.

Steroid hormone concentrations and body mass are differently affected by polyunsaturated fatty acids during the oestrous cycle in guinea pigs.

Reproductive functions in female mammals can be significantly affected by the actions of dietary polyunsaturated fatty acids (PUFAs) on steroid hormone secretion rates. Nevertheless, the effects of plasma free PUFAs on the oestrous cycle have seldom been considered. Therefore, in the present study, the diet of domestic guinea pigs was supplemented with high concentrations of different PUFAs and the effects of altered plasma PUFA patterns on steroid hormone concentrations, measured non-invasively, and body mass during oestrus and dioestrus were analysed. The oestrous cycle was characterised by increased oestrogen and cortisol concentrations in oestrus, corroborated by lowest bodyweight, whereas progesterone concentrations were highest in dioestrus. Plasma concentrations of the long-chain PUFAs docosahexaenoic acid (DHA; 22:6 ω3) and arachidonic acid (AA; 20:5 ω6) affected steroid hormone concentrations differently in oestrus and dioestrus. DHA positively affected oestrogen and progesterone concentrations and diminished cortisol concentrations only in oestrus. In contrast, AA negatively affected oestrogen and stimulated cortisol concentrations in oestrus and reduced progesterone concentrations in general. These findings imply selective and opposite contributions of DHA and AA to ovarian functions during different stages of the oestrous cycle, indicating a high biological relevance of plasma free PUFAs in female reproductive function.

Effects of food store quality on hibernation performance in common hamsters.

Hibernating animals can adjust torpor expression according to available energy reserves. Besides the quantity, the quality of energy reserves could play an important role for overwintering strategies. Common hamsters are food-storing hibernators and show high individual variation in hibernation performance, which might be related to the quality of food hoards in the hibernacula. In this study, we tested the effects of food stores high in fat content, particularly polyunsaturated fatty acids (PUFAs), on hibernation patterns under laboratory conditions. Control animals received standard rodent pellets only, while in the other group pellets were supplemented with sunflower seeds. We recorded body temperature during winter using subcutaneously implanted data loggers, documented total food consumption during winter, and analysed PUFA proportions in white adipose tissue (WAT) before and after the winter period. About half of the individuals in both groups hibernated and torpor expression did not differ between these animals. Among the high-fat group, however, individuals with high sunflower seeds intake strongly reduced the time spent in deep torpor. PUFA proportions in WAT decreased during winter in both groups and this decline was positively related to the time an individual spent in deep torpor. Sunflower seeds intake dampened the PUFA decline resulting in higher PUFA levels in animals of the high-fat group after winter. In conclusion, our results showed that common hamsters adjusted torpor expression and food intake in relation to the total energy of food reserves, underlining the importance of food hoard quality on hibernation performance.

Vitamin E Modifies High-Fat Diet-Induced Increase of DNA Strand Breaks, and Changes in Expression and DNA Methylation of Dnmt1 and MLH1 in C57BL/6J Male Mice.

Obesity is associated with low-grade inflammation, increased ROS production and DNA damage. Supplementation with antioxidants might ameliorate DNA damage and support epigenetic regulation of DNA repair. C57BL/6J male mice were fed a high-fat (HFD) or a control diet (CD) with and without vitamin E supplementation (4.5 mg/kg body weight (b.w.)) for four months. DNA damage, DNA promoter methylation and gene expression of Dnmt1 and a DNA repair gene (MLH1) were assayed in liver and colon. The HFD resulted in organ specific changes in DNA damage, the epigenetically important Dnmt1 gene, and the DNA repair gene MLH1. Vitamin E reduced DNA damage and showed organ-specific effects on MLH1 and Dnmt1 gene expression and methylation. These results suggest that interventions with antioxidants and epigenetic active food ingredients should be developed as an effective prevention for obesity-and oxidative stress-induced health risks.

Reproductive performance and gestational effort in relation to dietary fatty acids in guinea pigs.

BACKGROUND: Dietary saturated (SFAs) and polyunsaturated (PUFAs) fatty acids can highly affect reproductive functions by providing additional energy, modulating the biochemical properties of tissues, and hormone secretions. In precocial mammals such as domestic guinea pigs the offspring is born highly developed. Gestation might be the most critical reproductive period in this species and dietary fatty acids may profoundly influence the gestational effort. We therefore determined the hormonal status at conception, the reproductive success, and body mass changes during gestation in guinea pigs maintained on diets high in PUFAs or SFAs, or a control diet. RESULTS: The diets significantly affected the females' plasma fatty acid status at conception, while cortisol and estrogen levels did not differ among groups. SFA females exhibited a significantly lower body mass and litter size, while the individual birth mass of pups did not differ among groups and a general higher pup mortality rate in larger litters was diminished by PUFAs and SFAs. The gestational effort, determined by a mother's body mass gain during gestation, increased with total litter mass, whereas this increase was lowest in SFA and highest in PUFA individuals. The mother's body mass after parturition did not differ among groups and was positively affected by the total litter mass in PUFA females. CONCLUSIONS: While SFAs reduce the litter size, but also the gestational effort as a consequence, PUFA supplementation may contribute to an adjustment of energy accumulations to the total litter mass, which may both favor a mother's body condition at parturition and perhaps increase the offspring survival at birth.

Bilirubin Decreases Macrophage Cholesterol Efflux and ATP-Binding Cassette Transporter A1 Protein Expression.

BACKGROUND: Mild but chronically elevated circulating unconjugated bilirubin is associated with reduced total and low-density lipoprotein cholesterol concentration, which is associated with reduced cardiovascular disease risk. We aimed to investigate whether unconjugated bilirubin influences macrophage cholesterol efflux, as a potential mechanism for the altered circulating lipoprotein concentrations observed in hyperbilirubinemic individuals. METHODS AND RESULTS: Cholesterol efflux from THP-1 macrophages was assessed using plasma obtained from normo- and hyperbilirubinemic (Gilbert syndrome) humans (n=60 per group) or (heterozygote/homozygote Gunn) rats (n=20 per group) as an acceptor. Hyperbilirubinemic plasma from patients with Gilbert syndrome and Gunn rats induced significantly reduced cholesterol efflux compared with normobilirubinemic plasma. Unconjugated bilirubin (3-17.1 µmol/L) exogenously added to plasma- or apolipoprotein A1-supplemented media also decreased macrophage cholesterol efflux in a concentration- and time-dependent manner. We also showed reduced protein expression of the ATP-binding cassette transporter A1 (ABCA1), a transmembrane cholesterol transporter involved in apolipoprotein A1-mediated cholesterol efflux, in THP-1 macrophages treated with unconjugated bilirubin and in peripheral blood mononuclear cells obtained from hyperbilirubinemic individuals. Furthermore, we demonstrated that bilirubin accelerates the degradation rate of the ABCA1 protein in THP-1 macrophages. CONCLUSIONS: Cholesterol efflux from THP-1 macrophages is decreased in the presence of plasma obtained from humans and rats with mild hyperbilirubinemia. A direct effect of unconjugated bilirubin on cholesterol efflux was demonstrated and is associated with decreased ABCA1 protein expression. These data improve our knowledge concerning bilirubin's impact on cholesterol transport and represent an important advancement in our understanding of bilirubin's role in cardiovascular disease.