Publications by authors named "Gerald Rimbach"

241 Publications

Biomarkers of geroprotection and cardiovascular health: An overview of omics studies and established clinical biomarkers in the context of diet.

Crit Rev Food Sci Nutr 2021 Oct 14:1-21. Epub 2021 Oct 14.

Junior Research Group Translational Bioinformatics, Institute for Biostatistics and Informatics in Medicine and Ageing Research, Rostock University Medical Center, Rostock, Germany.

The slowdown, inhibition, or reversal of age-related decline (as a composite of disease, dysfunction, and, ultimately, death) by diet or natural compounds can be defined as . While there is no single reliable biomarker to judge the effects of dietary geroprotection, biomarker signatures based on omics (epigenetics, gene expression, microbiome composition) are promising candidates. Recently, omic biomarkers started to supplement established clinical ones such as lipid profiles and inflammatory cytokines. In this review, we focus on human data. We first summarize the current take on genetic biomarkers based on epidemiological studies. However, most of the remaining biomarkers that we describe, whether omics-based or clinical, are related to intervention studies. Then, because of their promising potential in the context of dietary geroprotection, we focus on the effects of berry-based interventions, which up to now have been mostly described employing clinical markers. We provide an aggregation and tabulation of all the recent systematic reviews and meta-analyses that we could find related to this topic. Finally, we present evidence for the importance of the "nutribiography," that is, the influence that an individual's history of diet and natural compound consumption can have on the effects of dietary geroprotection.
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http://dx.doi.org/10.1080/10408398.2021.1975638DOI Listing
October 2021

Urinary Carnosinase-1 Excretion is Associated with Urinary Carnosine Depletion and Risk of Graft Failure in Kidney Transplant Recipients: Results of the TransplantLines Cohort Study.

Antioxidants (Basel) 2021 Jul 9;10(7). Epub 2021 Jul 9.

Department of Internal Medicine, University Medical Center Groningen, University of Groningen, 9700 RB Groningen, The Netherlands.

Carnosine affords protection against oxidative and carbonyl stress, yet high concentrations of the carnosinase-1 enzyme may limit this. We recently reported that high urinary carnosinase-1 is associated with kidney function decline and albuminuria in patients with chronic kidney disease. We prospectively investigated whether urinary carnosinase-1 is associated with a high risk for development of late graft failure in kidney transplant recipients (KTRs). Carnosine and carnosinase-1 were measured in 24 h urine in a longitudinal cohort of 703 stable KTRs and 257 healthy controls. Cox regression was used to analyze the prospective data. Urinary carnosine excretions were significantly decreased in KTRs (26.5 [IQR 21.4-33.3] µmol/24 h versus 34.8 [IQR 25.6-46.8] µmol/24 h; < 0.001). In KTRs, high urinary carnosinase-1 concentrations were associated with increased risk of undetectable urinary carnosine (OR 1.24, 95%CI [1.06-1.45]; = 0.007). During median follow-up for 5.3 [4.5-6.0] years, 84 (12%) KTRs developed graft failure. In Cox regression analyses, high urinary carnosinase-1 excretions were associated with increased risk of graft failure (HR 1.73, 95%CI [1.44-2.08]; < 0.001) independent of potential confounders. Since urinary carnosine is depleted and urinary carnosinase-1 imparts a higher risk for graft failure in KTRs, future studies determining the potential of carnosine supplementation in these patients are warranted.
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http://dx.doi.org/10.3390/antiox10071102DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8301129PMC
July 2021

Boron Contents of German Mineral and Medicinal Waters and Their Bioavailability in Drosophila melanogaster and Humans.

Mol Nutr Food Res 2021 08 20;65(15):e2100345. Epub 2021 Jun 20.

Institute of Human Nutrition and Food Science, University of Kiel, Kiel, Germany.

Scope: Boron is a trace element that naturally occurs in soil, making mineral and medicinal water important contributors to overall intake. Thus, in a systematic screening, the mean boron concentrations of 381 German mineral and medicinal waters are determined.

Methods And Results: Boron concentrations in mineral and medicinal waters are analyzed by inductively coupled mass spectrometry (ICP-MS). Highest boron values find in waters from the southwest of Germany. The boron content of the waters is positively correlated with the concentration of most other analyzed bulk elements, including calcium, potassium, magnesium, and sodium. Mineral waters with either low (7.9 µg L ), medium (113.9 µg L ), or high (2193.3 µg L ) boron content are chosen for boron exposure experiments in fruit flies (Drosophila melanogaster) and humans. In flies, boron-rich mineral water significantly increases boron accumulation, with the accumulation predominantly occurring in the exoskeleton. In humans, serum boron and 24-h urinary boron excretion significantly increase only in response to the intake of boron-rich mineral water.

Conclusion: Overall, the current data demonstrate that mineral and medicinal waters vary substantially in the content of boron and that boron-rich mineral water can be used to elevate the boron status, both in flies and humans.
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http://dx.doi.org/10.1002/mnfr.202100345DOI Listing
August 2021

Cyclodextrins, Natural Compounds, and Plant Bioactives-A Nutritional Perspective.

Biomolecules 2021 03 9;11(3). Epub 2021 Mar 9.

Institute of Human Nutrition and Food Science, University of Kiel, Hermann-Rodewald-Strasse 6, 24118 Kiel, Germany.

Cyclodextrins (CDs) are a group of cyclic oligosaccharides produced from starch or starch derivatives. They contain six (αCD), seven (βCD), eight (γCD), or more glucopyranose monomers linked via α-1,4-glycosidic bonds. CDs have a truncated cone shape with a hydrophilic outer wall and a less hydrophilic inner wall, the latter forming a more apolar internal cavity. Because of this special architecture, CDs are soluble in water and can simultaneously host lipophilic guest molecules. The major advantage of inclusion into CDs is increased aqueous solubility of such lipophilic substances. Accordingly, we present studies where the complexation of natural compounds such as propolis and dietary plant bioactives (e.g., tocotrienol, pentacyclic triterpenoids, curcumin) with γCD resulted in improved stability, bioavailability, and bioactivity in various laboratory model organisms and in humans. We also address safety aspects that may arise from increased bioavailability of plant extracts or natural compounds owing to CD complexation. When orally administered, α- and βCD-which are inert to intestinal digestion-are fermented by the human intestinal flora, while γCD is almost completely degraded to glucose units by α-amylase. Hence, recent reports indicate that empty γCD supplementation exhibits metabolic activity on its own, which may provide opportunities for new applications.
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http://dx.doi.org/10.3390/biom11030401DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7998733PMC
March 2021

The Potential of Resveratrol to Act as a Caloric Restriction Mimetic Appears to Be Limited: Insights from Studies in Mice.

Adv Nutr 2021 06;12(3):995-1005

Institute of Human Nutrition and Food Science, University of Kiel, Kiel, Germany.

Caloric restriction (CR) has been shown repeatedly to prolong the lifespan in laboratory animals, with its benefits dependent on molecular targets forming part of the nutrient signaling network, including the NAD-dependent deacetylase silent mating type information regulation 2 homologue 1 (SIRT1). It has been hypothesized that the stilbene resveratrol (RSV) may counteract age- and obesity-related diseases similarly to CR. In yeast and worms, RSV-promoted longevity also depended on SIRT1. While it remains unclear whether RSV can prolong lifespans in mammals, some studies in rodents supplemented with RSV have reported lowered body weight (BW) and fat mass, improved insulin sensitivity, lowered cholesterol levels, increased fitness, and mitochondrial biogenesis. Molecular mechanisms possibly leading to such changes include altered gene transcription and activation of SIRT1, AMP-activated kinase (AMPK), and peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PPARGC1A). However, some mouse models did not benefit from RSV treatment to the same extent as others. We conducted a literature search on PubMed (15 April, 2020) for trials directly comparing RSV application to CR feeding in mice. In most studies retrieved by this systematic PubMed search, mice supplemented with RSV did not show significant reductions of BW, glucose, or insulin. Moreover, in some of these studies, RSV and CR treatments affected molecular targets differently and/or findings on RSV and CR impacts varied between trials. We discuss those RSV-induced changes in gene transcription hypothesized to partly counteract age-related alterations. Although there may be a moderate effect of RSV supplementation on parameters such as insulin sensitivity toward a more CR-like profile in mice, data are inconsistent. Likewise, RSV supplementation trials in humans report controversial findings. While we consider that RSV may, under certain circumstances, moderately mimic some aspects of CR, current evidence does not fully support its use to prevent or treat age- or obesity-related diseases.
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http://dx.doi.org/10.1093/advances/nmaa148DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8166566PMC
June 2021

Engineering of a functional γ-tocopherol transfer protein.

Redox Biol 2021 01 4;38:101773. Epub 2020 Nov 4.

University of Bern, Department of Chemistry and Biochemistry, Bern, 3012, Switzerland. Electronic address:

α-tocopherol transfer protein (TTP) was previously reported to self-aggregate into 24-meric spheres (α-TTP) and to possess transcytotic potency across mono-layers of human umbilical vein endothelial cells (HUVECs). In this work, we describe the characterisation of a functional TTP variant with its vitamer selectivity shifted towards γ-tocopherol. The shift was obtained by introducing an alanine to leucine substitution into the substrate-binding pocket at position 156 through site directed mutagenesis. We report here the X-ray crystal structure of the γ-tocopherol specific particle (γ-TTP) at 2.24 Å resolution. γ-TTP features full functionality compared to its α-tocopherol specific parent including self-aggregation potency and transcytotic activity in trans-well experiments using primary HUVEC cells. The impact of the A156L mutation on TTP function is quantified in vitro by measuring the affinity towards γ-tocopherol through micro-differential scanning calorimetry and by determining its ligand-transfer activity. Finally, cell culture experiments using adherently grown HUVEC cells indicate that the protomers of γ-TTP, in contrast to α-TTP, do not counteract cytokine-mediated inflammation at a transcriptional level. Our results suggest that the A156L substitution in TTP is fully functional and has the potential to pave the way for further experiments towards the understanding of α-tocopherol homeostasis in humans.
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http://dx.doi.org/10.1016/j.redox.2020.101773DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7677715PMC
January 2021

Taurine Enhances Iron-Related Proteins and Reduces Lipid Peroxidation in Differentiated C2C12 Myotubes.

Antioxidants (Basel) 2020 Oct 31;9(11). Epub 2020 Oct 31.

Institute of Human Nutrition and Food Science, University of Kiel, 24118 Kiel, Germany.

Taurine is a nonproteinogenic amino sulfonic acid in mammals. Interestingly, skeletal muscle is unable to synthesize taurine endogenously, and the processing of muscular taurine changes throughout ageing and under specific pathophysiological conditions, such as muscular dystrophy. Ageing and disease are also associated with altered iron metabolism, especially when there is an excess of labile iron. The present study addresses the question of whether taurine connects cytoprotective effects and redox homeostasis in a previously unknown iron-dependent manner. Using cultured differentiated C2C12 myotubes, the impact of taurine on markers of lipid peroxidation, redox-sensitive enzymes and iron-related proteins was studied. Significant increases in the heme protein myoglobin and the iron storage protein ferritin were observed in response to taurine treatment. Taurine supplementation reduced lipid peroxidation and BODIPY oxidation by ~60 and 25%, respectively. Furthermore, the mRNA levels of redox-sensitive heme oxygenase the total cellular glutathione content were lower in taurine-supplemented cells than they were in the control cells. We suggest that taurine may inhibit the initiation and propagation of lipid peroxidation by lowering basal levels of cellular stress, perhaps through reduction of the cellular labile iron pool.
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http://dx.doi.org/10.3390/antiox9111071DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7693586PMC
October 2020

Chemical Composition, Bioactivity and Safety Aspects of Kuding Tea-From Beverage to Herbal Extract.

Nutrients 2020 Sep 12;12(9). Epub 2020 Sep 12.

Institute of Human Nutrition and Food Science, University of Kiel, Hermann-Rodewald-Strasse 6, 24118 Kiel, Germany.

Kuding tea (KT) is a bitter-tasting herbal tea that has been commonly used in traditional Chinese medicine (TCM). The large-leaved Ku-Ding-Cha (Aquifoliaceae) is composed of its representative species Thunb and C.J. Tseng. Because of its potential lipid-lowering, body weight-reducing and blood-glucose-lowering properties, KT has increasingly been recognised for its importance over the past several decades. KT is no longer used only as a beverage, and various extraction methods have been applied to obtain aqueous and ethanolic KT extracts (KTE) or their fractions, which could potentially be used as dietary supplements. The major bioactive components of KT are triterpene saponins and polyphenols, but the composition of KT differs substantially between and among the different KT species. This in turn might affect the physiological effects of KT. KT exhibits antiobesity properties, possibly partly by affecting the intestinal microbiota. In addition, KT may mediate putative antioxidative, anti-inflammatory and anticancer activities. However, there is evidence that high KTE supplementation can adversely affect liver metabolism. The physiological relevance of KT in humans remains rather unclear since the potential health benefits of KT and its constituents reviewed here are mainly derived on the basis of in vitro and animal studies.
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http://dx.doi.org/10.3390/nu12092796DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7551553PMC
September 2020

Plasma Lithium Levels in a General Population: A Cross-Sectional Analysis of Metabolic and Dietary Correlates.

Nutrients 2020 Aug 18;12(8). Epub 2020 Aug 18.

Institute of Epidemiology, Kiel University, 24105 Kiel, Germany.

Initial evidence suggests that lithium might affect life expectancy and the risk for different disease conditions, but most studies were conducted in patients on lithium medication. Little is known about the association of blood lithium levels within the physiological range with cardiometabolic risk factors and diet. We measured plasma lithium in a community-based sample from Northern Germany (samples taken between 2010 and 2012). All participants (aged 25-82 years) underwent standardized examinations and completed a semi-quantitative food frequency questionnaire. Of several variables tested, the estimated glomerular filtration rate (eGFR) was statistically significantly (inversely) associated with lithium levels, mainly in individuals with slightly impaired renal function (eGFR < 75 mL/min/1.73 m). Besides, lithium levels were positively associated with age and alcohol intake. Using reduced rank regression, we identified a dietary pattern explaining 8.63% variation in plasma lithium levels. Higher lithium levels were associated with higher intakes of potatoes, leafy vegetables, root vegetables, fruits, tea, beer, wine and dietetic products and lower intakes of pasta, rice, pork, chocolate, sweets, soft drinks, other alcoholic beverages, sauces and snacks. Our observations suggest that plasma lithium levels are associated inversely with kidney function, particularly in individuals with slightly impaired renal function, and positively with age and alcohol intake. Lithium at physiological levels was moderately related to an exploratory dietary pattern.
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http://dx.doi.org/10.3390/nu12082489DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7468710PMC
August 2020

Historical Reflection of Food Processing and the Role of Legumes as Part of a Healthy Balanced Diet.

Foods 2020 Aug 4;9(8). Epub 2020 Aug 4.

Institute of Human Nutrition and Food Science, University of Kiel, 24118 Kiel, Germany.

The purpose of food processing has changed over time. High-intensity industrially processed food often exhibits higher concentrations of added sugar, salt, higher energy, and lower micronutrient density than does similar food or meals prepared at home from raw or minimally processed food. Viewing the evolution of food processing from history, one could make out three major transitions related to human socioeconomic changes. The first transition was marked by the change from hunting and gathering to settled societies with agriculture and livestock farming. The second and third transitions were associated with the Industrial Revolution and with market liberalization, global trade and automation, respectively. The next major transition that will influence food processing and shape human nutrition may include the exploitation of sustainable and efficient protein and food sources that will ensure high-quality food production for the growing world population. Apart from novel food sources, traditional food such as legumes and pulses likewise exhibit great potential to contribute to a healthy balanced diet. The promotion of legumes should be intensified in public dietary guidelines because their consumption is rather low in high-income countries and increasingly displaced as a traditional staple by industrially processed food in low- to middle-income countries.
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http://dx.doi.org/10.3390/foods9081056DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7466326PMC
August 2020

Lithium Content of 160 Beverages and Its Impact on Lithium Status in .

Foods 2020 Jun 17;9(6). Epub 2020 Jun 17.

Institute of Human Nutrition and Food Science, University of Kiel, 24118 Kiel, Germany.

Lithium (Li) is an important micronutrient in human nutrition, although its exact molecular function as a potential essential trace element has not yet been fully elucidated. It has been previously shown that several mineral waters are rich and highly bioavailable sources of Li for human consumption. Nevertheless, little is known about the extent in which other beverages contribute to the dietary Li supply. To this end, the Li content of 160 different beverages comprising wine and beer, soft and energy drinks and tea and coffee infusions was analysed by inductively coupled plasma mass spectrometry (ICP-MS). Furthermore, a feeding study in was conducted to test whether Li derived from selected beverages changes Li status in flies. In comparison to the average Li concentration in mineral waters (108 µg/L; reference value), the Li concentration in wine (11.6 ± 1.97 µg/L) and beer (8.5 ± 0.77 µg/L), soft and energy drinks (10.2 ± 2.95 µg/L), tea (2.8 ± 0.65 µg/L) and coffee (0.1 ± 0.02 µg/L) infusions was considerably lower. Only Li-rich mineral water (~1600 µg/L) significantly increased Li concentrations in male and female flies. Unlike mineral water, most wine and beer, soft and energy drink and tea and coffee samples were rather Li-poor food items and thus may only contribute to a moderate extent to the dietary Li supply. A novelty of this study is that it relates analytical Li concentrations in beverages to Li whole body retention in .
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http://dx.doi.org/10.3390/foods9060795DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7353479PMC
June 2020

Furbellow (Brown Algae) Extract Increases Lifespan in by Interfering with TOR-Signaling.

Nutrients 2020 Apr 22;12(4). Epub 2020 Apr 22.

Department of Molecular Physiology, Kiel University, D-24098 Kiel, Germany.

Algal products are well known for their health promoting effects. Nonetheless, an in depth understanding of the underlying molecular mechanisms is still only fragmentary. Here, we show that aqueous furbelow extracts (brown algae, ) lengthen the life of both sexes of the fruit fly substantially, if used as nutritional additives to conventional food. This life prolonging effect became even more pronounced in the presence of stressors, such as high-fat dieting of living under drought conditions. Application of the extracts did not change food intake, excretion, or other major physiological parameters. Nevertheless, effects on the intestinal microbiota were observed, leading to an increased species richness, which is usually associated with healthy conditions. Lifespan extension was not observed in target of rapamycin (TOR)-deficient animals, implying that functional TOR signaling is necessary to unfold the positive effects of brown algae extract (BAE) on this important trait. The lack of life lengthening in animals with deregulated TOR signaling exclusively targeted to body fat showed that this major energy storage organ is instrumental for transmitting these effects. In addition, expression of (), an effective inhibitor of insulin signaling implies that BAE exerts their positive effects through interaction with the tightly interwoven TOR- and insulin-signaling systems, although insulin levels were not directly affected by this intervention.
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http://dx.doi.org/10.3390/nu12041172DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7230866PMC
April 2020

In Contrast to Dietary Restriction, Application of Resveratrol in Mice Does not Alter Mouse Major Urinary Protein Expression.

Nutrients 2020 Mar 19;12(3). Epub 2020 Mar 19.

Institute of Human Nutrition and Food Science, University of Kiel, Hermann-Rodewald-Straße 6, 24118 Kiel, Germany.

Resveratrol (RSV) supplementation in mice has been discussed as partly mimicking the beneficial effects of dietary restriction (DR). However, data on putative benefits from resveratrol application in mice and other model organisms including humans is contradictory. Mouse major urinary proteins (MUPs) are a family of proteins that are expressed in rodent liver and secreted via urine. Impacting (mating) behavior and pheromone communication, they are severely down-regulated upon DR. We carried out two studies in C57BL/6Rj mice where RSV was either supplemented via diet or injected intraperitoneally for 8 weeks. Contrary to -40% DR, RSV did not decrease total MUP protein expression or (amongst others , , , , and ) mRNA levels in mouse liver when compared to ad-libitum (AL)-fed controls. Since inhibitory glucocorticoid response elements can be found in promoters, we also measured glucocorticoid receptor (GR) levels in nuclear hepatic extracts. Consistent with differential MUP expression, we observed more nuclear GR in DR mice than in RSV-supplemented and AL control mice with no difference between RSV and AL. These findings point to the notion that, in mice, RSV does not mimic DR in terms of differential MUP expression.
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http://dx.doi.org/10.3390/nu12030815DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7146287PMC
March 2020

Supplementation with nitrate only modestly affects lipid and glucose metabolism in genetic and dietary-induced murine models of obesity.

J Clin Biochem Nutr 2020 Jan 12;66(1):24-35. Epub 2019 Nov 12.

Institute of Human Nutrition and Food Science, Food Science, University of Kiel, Hermann-Rodewald-Strasse 6, 24118 Kiel, Germany.

To gain a better understanding of how nitrate may affect carbohydrate and lipid metabolism, female wild-type mice were fed a high-fat, high-fructose diet supplemented with either 0, 400, or 800 mg nitrate/kg diet for 28 days. Additionally, obese female mice were fed a 5% fat diet supplemented with the same levels and source of nitrate. Nitrate decreased the sodium-dependent uptake of glucose by ileal mucosa in wild-type mice. Moreover, nitrate significantly decreased triglyceride content and mRNA expression levels of in liver and in skeletal muscle. Oral glucose tolerance as well as plasma cholesterol, triglyceride, insulin, leptin, glucose and the activity of ALT did not significantly differ between experimental groups but was higher in mice than in wild-type mice. Nitrate changed liver fatty acid composition and mRNA levels of only slightly. Further hepatic genes encoding proteins involved in lipid and carbohydrate metabolism were not significantly different between the three groups. Biomarkers of inflammation and autophagy in the liver were not affected by the different dietary treatments. Overall, the present data suggest that short-term dietary supplementation with inorganic nitrate has only modest effects on carbohydrate and lipid metabolism in genetic and dietary-induced mouse models of obesity.
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http://dx.doi.org/10.3164/jcbn.19-43DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6983433PMC
January 2020

The Putative Caloric Restriction Mimetic Resveratrol has Moderate Impact on Insulin Sensitivity, Body Composition, and the Metabolome in Mice.

Mol Nutr Food Res 2020 03 11;64(6):e1901116. Epub 2020 Feb 11.

Institute of Human Nutrition and Food Science, University of Kiel, Hermann-Rodewald-Straße 6, 24118, Kiel, Germany.

Scope: Data on resveratrol-(trans-3,5,4'-trihydroxystilbene)-induced caloric-restriction-(CR)-mimicking effects in mice receiving a high-fat diet (HFD) are contradictory. It is hypothesized that this can possibly stem from different bioactivities of resveratrol (RSV) microbial metabolites.

Methods And Results: C57BL/6Rj mice are fed an ad-libitum HFD supplemented with RSV or its metabolites, dihydroresveratrol (DHR) and lunularin (LUN) (≈28 mg (dihydro)stilbene kg mouse per day). A 40% CR group was included in the study. While CR mice show robust changes in bodyweight and composition, hormone levels and mRNA expression, slight changes are found (more muscle, less adipose tissue) in body composition, leptin, and insulin levels in RSV-supplemented mice compared to ad libitum controls. LUN hardly and DHR does not change the hormone levels measured. Metabolome analysis of serum shows changes in CR mice but only slight, if any, changes in RSV-, DHR-, or LUN-supplemented mice compared to the controls. Evaluating the capability of RSV and its metabolites to inhibit carbohydrate-hydrolyzing enzymes in vitro, it is found that RSV reduced α-glucosidase activity to a stronger extent than DHR and LUN.

Conclusion: Decelerated carbohydrate breakdown by RSV may have contributed to the moderate impact of dietary RSV on mouse insulin sensitivity (lowered fasting and post-glucose-bolus insulin levels).
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http://dx.doi.org/10.1002/mnfr.201901116DOI Listing
March 2020

High Dietary Kuding Tea Extract Supplementation Induces Hepatic Xenobiotic-Metabolizing Enzymes-A 6-Week Feeding Study in Mice.

Nutrients 2019 Dec 22;12(1). Epub 2019 Dec 22.

Institute of Human Nutrition and Food Science, University of Kiel, Hermann-Rodewald-Strasse 6, 24118 Kiel, Germany.

Kuding tea (KT) is a traditional Chinese beverage rich in plant bioactives that may exhibit various health benefits. However, little is known about the safety of KT extract (KTE) when consumed long term at high doses as a dietary supplement. Therefore, in this study, we investigated aspects of the safety of KTE. Male C57BL/6 mice were fed a high-fat, high-fructose, Western-type diet (control) supplemented with either 12.88% γ-cyclodextrin (γCD), 7.12% KTE (comprising 0.15% ursolic acid, UA) encapsulated in 12.88% γCD (KTE-γCD), or 0.15% UA over a 6-week experimental period. The dietary treatments did not affect food intake, body weight or body composition. However, treatment with KTE-γCD, but not γCD and UA, increased liver weight and hepatic fat accumulation, which was accompanied by increased hepatic PPARγ and CD36 mRNA levels. KTE-γCD treatment elevated plasma cholesterol and CYP7A1 mRNA and protein levels compared to those in control mice. KTE-γCD substantially increased the mRNA and protein levels of hepatic CYP3A and GSTA1, which are central to the detoxification of drugs and xenobiotics. Furthermore, we observed a moderate elevation in hepatic CYP3A (5-fold change) and GSTA1 (1.7-fold change) mRNA levels in UA-fed mice. In vitro data collected in HepG2 cells indicated a dose-dependent increase in hepatic cytotoxicity in response to KTE treatment, which may have been partly mediated by UA. Overall, the present data may contribute to the safety assessment of KTE and suggest that KTE encapsulated in γCD affects liver fat storage and the hepatic phase I and phase II responses in mice.
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http://dx.doi.org/10.3390/nu12010040DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7019617PMC
December 2019

The Effects of Anthocyanins and Their Microbial Metabolites on the Expression and Enzyme Activities of Paraoxonase 1, an Important Marker of HDL Function.

Nutrients 2019 Nov 24;11(12). Epub 2019 Nov 24.

Food Innovation & Health, Quadram Institute Bioscience, Norwich Research Park, Norwich, Norfolk NR4 7UA, UK.

High circulating HDL concentrations and measures of various HDL functions are inversely associated with cardiovascular disease (CVD) risk. Paraoxonase 1 (PON1) contributes to many of the athero-protective functions of HDL, such as promoting the reverse cholesterol transport process and reducing the levels of oxidized LDL. PON1 activities are influenced by several factors, the most important being diet and genetic polymorphisms. Reported data from randomized controlled trials have shown that anthocyanin consumption increased PON1 activity. However, the underlying molecular mechanisms by which anthocyanins increase PON1 activity are not understood. Therefore, the aim of this research was to investigate the ability of anthocyanins and their metabolites to increase gene expression and/or enzyme activities as potential mechanisms. The effect of the two predominant dietary anthocyanins and 18 of their recently identified microbial metabolites including their phase-II conjugates on gene expression was studied using a PON1-Huh7 stably-transfected cell line and reporter gene assay. The effects of these compounds on PON1 arylesterase and lactonase activities were investigated using two isoforms of the PON1 enzyme that are the phenotypes of the 192Q/R polymorphism. None of the compounds caused even modest changes in PON1 promoter activity ( ≥ 0.05). Further, none of the compounds at physiological concentrations caused any significant changes in the arylesterase or lactonase activity of either of the iso-enzymes. Cyanidin reduced the lactonase activity of the PON1-R192R enzyme at high concentrations (-22%, < 0.001), but not at physiologically achievable concentrations. In conclusion, none of the data reported here support the notion that anthocyanins or their metabolites affect PON1 transactivation or enzyme activities.
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http://dx.doi.org/10.3390/nu11122872DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6950676PMC
November 2019

Urinary Taurine Excretion and Risk of Late Graft Failure in Renal Transplant Recipients.

Nutrients 2019 Sep 13;11(9). Epub 2019 Sep 13.

Department of Internal Medicine, University Medical Center Groningen, University of Groningen, 9713 GZ Groningen, The Netherlands.

Taurine is a sulfur containing nutrient that has been shown to protect against oxidative stress, which has been implicated in the pathophysiology leading to late graft failure after renal transplantation. We prospectively investigated whether high urinary taurine excretion, reflecting high taurine intake, is associated with low risk for development of late graft failure in renal transplant recipients (RTR). Urinary taurine excretion was measured in a longitudinal cohort of 678 stable RTR. Prospective associations were assessed using Cox regression analyses. Graft failure was defined as the start of dialysis or re-transplantation. In RTR (58% male, 53 ± 13 years old, estimated glomerular filtration rate (eGFR) 45 ± 19 mL/min/1.73 m), urinary taurine excretion (533 (210-946) µmol/24 h) was significantly associated with serum free sulfhydryl groups (β = 0.126; = 0.001). During median follow-up for 5.3 (4.5-6.0) years, 83 (12%) patients developed graft failure. In Cox regression analyses, urinary taurine excretion was inversely associated with graft failure (hazard ratio: 0.74 (0.67-0.82); < 0.001). This association remained significant independent of potential confounders. High urinary taurine excretion is associated with low risk of late graft failure in RTR. Therefore, increasing taurine intake may potentially support graft survival in RTR. Further studies are warranted to determine the underlying mechanisms and the potential of taurine supplementation.
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http://dx.doi.org/10.3390/nu11092212DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6770760PMC
September 2019

Combined effects of nutritional, biochemical and environmental stimuli on growth performance and fatty acid composition of gilthead sea bream (Sparus aurata).

PLoS One 2019 14;14(5):e0216611. Epub 2019 May 14.

GMA-Gesellschaft für Marine Aquakultur mbH, Büsum, Germany.

The reliance of the aquafeed industry on marine resources has to be reduced by innovative approaches in fish nutrition. Thus, a three-factorial approach (fish oil reduced diet, phytochemical genistein, and temperature reduction) was chosen to investigate the interaction of effects on growth performance and tissue omega-3 long chain polyunsaturated fatty acid (LC-PUFA) levels in juvenile sea bream (Sparus aurata, 12.5 ± 2.2 g). Genistein is a phytoestrogen with estrogen-like activity and thus LC-PUFA increasing potential. A decrease in the rearing temperature was chosen based on the positive effects of low temperature on fish lipid quality. The experimental diets were reduced in marine ingredients and had a fish oil content of either 6% dry matter (DM; F6: positive control) or 2% DM (F2: negative control) and were administered in the plain variant or with inclusion of 0.15% DM genistein (F6 + G and F2 + G). The feeding trial was performed simultaneously at 23°C and 19°C. The results indicated that solely temperature had a significant effect on growth performance and whole body nutrient composition of sea bream. Nevertheless, the interaction of all three factors significantly affected the fatty acid compositions of liver and fillet tissue. Most importantly, they led to a significant increase by 4.3% of fillet LC-PUFA content in sea bream fed with the diet F6 + G in comparison to control fish fed diet F6, when both groups were held at 19°C. It is hypothesized that genistein can act via estrogen-like as well as other mechanisms and that the dietary LC-PUFA content may impact its mode of action. Temperature most likely exhibited its effects indirectly via altered growth rates and metabolism. Although effects of all three factors and of genistein in particular were only marginal, they highlight a possibility to utilize the genetic capacity of sea bream to improve tissue lipid quality.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0216611PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6516738PMC
January 2020

A Natural mtDNA Polymorphism in Complex III Is a Modifier of Healthspan in Mice.

Int J Mol Sci 2019 May 13;20(9). Epub 2019 May 13.

Luebeck Institute of Experimental Dermatology and Center for research of inflammatory skin disease (CRIS), University of Luebeck, 23562 Luebeck, Germany.

In this study, we provide experimental evidence that a maternally inherited polymorphism in the mitochondrial cytochrome b gene (; m.15124A>G, Ile-Val) in mitochondrial complex III resulted in middle-aged obesity and higher susceptibility to diet-induced obesity, as well as age-related inflammatory disease, e.g., ulcerative dermatitis, in mice. As a consequence of the gene variation, we observed alterations in body composition, metabolism and mitochondrial functions, i.e., increased mitochondrial oxygen consumption rate and higher levels of reactive oxygen species, as well as in the commensal bacterial composition in the gut, with higher abundance of Proteobacteria in mice carrying the variant. These observations are in line with the previously described links of the mitochondrial complex III gene with obesity and metabolic diseases in humans. Given that these functional changes by the G variant at m.15124 in the are already present in young mice that were kept under normal condition, it is plausible that the m.15124A>G variant is a disease susceptibility modifier to the diseases induced by additional stressors, i.e., dietary and/or aging stress, and that the variant results in the higher incidence of clinical diseases presentation in C57BL/6J-mt than C57BL/6J mice. Thus, mtDNA variants could be potential biomarkers to evaluate the healthspan.
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http://dx.doi.org/10.3390/ijms20092359DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6539666PMC
May 2019

Lithium-Rich Mineral Water is a Highly Bioavailable Lithium Source for Human Consumption.

Mol Nutr Food Res 2019 May 3:e1900039. Epub 2019 May 3.

Kiel University, Institute of Human Nutrition and Food Science, Devision of Food Science, 24118, Kiel, Germany.

Scope: Lithium is an important trace element in human nutrition and medicine. Mineral and medicinal waters may represent a significant source of dietary lithium intake.

Methods And Results: The lithium concentration of 360 German mineral and 21 medicinal waters is determined. Based on a systematic screening, three different mineral waters exhibiting low (1.7 µg L ), medium (171 µg L ), and high lithium (1724 µg L ) concentrations are chosen for an acute bioavailability study in male healthy volunteers. In Germany, a north-east to south-west gradient of analyzed lithium concentrations is observed in the 381 tested waters. The lithium concentration in the water is significantly correlated with its sodium (r = 0. 810), potassium (r = 0.716), and magnesium (r = 0.361), but not with its calcium concentration. In a randomized cross-over trial, volunteers (n = 3×10 each) drink 1.5 L of the respective mineral waters, and lithium concentrations in serum and urine are monitored over 24 h. Consumption of the mineral waters with a medium and high lithium content results in a dose-dependent response in serum lithium concentrations and total urinary lithium excretion.

Conclusion: Lithium-rich mineral and medicinal waters may be an important and highly bioavailable lithium source for human consumption.
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http://dx.doi.org/10.1002/mnfr.201900039DOI Listing
May 2019

Plasma Malondialdehyde and Risk of New-Onset Diabetes after Transplantation in Renal Transplant Recipients: A Prospective Cohort Study.

J Clin Med 2019 Apr 4;8(4). Epub 2019 Apr 4.

Division of Nephrology, Department of Internal Medicine, University Medical Center Groningen, University of Groningen, 9713 GZ Groningen, The Netherlands.

New-onset diabetes after transplantation (NODAT) is a frequent complication in renal transplant recipients (RTR). Although oxidative stress has been associated with diabetes mellitus, data regarding NODAT are limited. We aimed to prospectively investigate the long-term association between the oxidative stress biomarker malondialdehyde (measured by high-performance liquid chromatography) and NODAT in an extensively phenotyped cohort of non-diabetic RTR with a functioning graft ≥1 year. We included 516 RTR (51 ± 13 years-old, 57% male). Median plasma malondialdehyde (MDA) was 2.55 (IQR, 1.92-3.66) µmol/L. During a median follow-up of 5.3 (IQR, 4.6-6.0) years, 56 (11%) RTR developed NODAT. In Cox proportional-hazards regression analyses, MDA was inversely associated with NODAT, independent of immunosuppressive therapy, transplant-specific covariates, lifestyle, inflammation, and metabolism parameters (HR, 0.55; 95% CI, 0.36-0.83 per 1-SD increase; < 0.01). Dietary antioxidants intake (e.g., vitamin E, α-lipoic acid, and linoleic acid) were effect-modifiers of the association between MDA and NODAT, with particularly strong inverse associations within the subgroup of RTR with relatively higher dietary antioxidants intake. In conclusion, plasma MDA concentration is inversely and independently associated with long-term risk of NODAT in RTR. Our findings support a potential underrecognized role of oxidative stress in post-transplantation glucose homeostasis.
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http://dx.doi.org/10.3390/jcm8040453DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6518172PMC
April 2019

Resveratrol, lunularin and dihydroresveratrol do not act as caloric restriction mimetics when administered intraperitoneally in mice.

Sci Rep 2019 03 14;9(1):4445. Epub 2019 Mar 14.

Institute of Human Nutrition and Food Science, University of Kiel, Hermann-Rodewald-Straße 6, 24118, Kiel, Germany.

Resveratrol as well as caloric restriction were shown to extend lifespan in some model organisms and may possibly delay onset of ageing-related diseases in humans. Yet, resveratrol supplementation does not always extend lifespan of animal models or improve health status of humans. Because of interindividual differences in human microbiota, resveratrol metabolite production in the gut differs. While some individuals produce lunularin and dihydroresveratrol in their gut, others produce dihydroresveratrol only. Therefore, we addressed the question whether these metabolites differ in their biological impact on ageing and intraperitoneally injected 13-month-old C57BL/6JRj mice on an ad-libitum (AL) HFD with resveratrol, dihydroresveratrol or lunularin (24 mg/kg bodyweight; 3 times/week). Compared to mice injected with vehicle (AL-control), resveratrol and dihydroresveratrol did not change bodyweight and had no impact on insulin or glucose levels while lunularin slightly reduced feed intake and bodyweight gain. CR-mice showed lowered cholesterol, insulin and leptin levels, elevated adiponectin and phosphorylated AMPK levels in liver as well as increased transcription of Pck1 and Pgc1α when compared to the AL-control. In contrast, injections with the test substances did not change these parameters. We therefore conclude that in our model, resveratrol, lunularin and dihydroresveratrol did not act as CR mimetics.
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http://dx.doi.org/10.1038/s41598-019-41050-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6418094PMC
March 2019

in nutrition research-the importance of standardizing experimental diets.

Genes Nutr 2019 1;14. Epub 2019 Feb 1.

1Institute of Human Nutrition and Food Science, University of Kiel, 24118 Kiel, Germany.

The fruit fly has been increasingly recognized as an important model organism in nutrition research. In order to conduct nutritional studies in fruit flies, special attention should be given to the composition of the experimental diets. Besides complex diets, which are often based on maize, yeast, sucrose, and agar, can be also fed chemically defined diets. These so-called holidic diets are standardized in terms of their macro- and micronutrient composition although the quantitative nutrient requirements of flies have yet not been fully established and warrant further investigations. For instance, only few studies address the fatty acid, vitamin, mineral, and trace element requirements of fruit flies. may be also of interest in the field of nutritional medicine. Diet-induced diabetes and obesity models have been established, and in this context, often, the so-called high-fat and high-sugar diets are fed. However, the composition of these diets is not sufficiently defined and varies between studies. A consensus within the scientific community needs to be reached to standardize the exact composition of experimental complex and holidic diets for in nutrition research. Since is an established valuable model system for numerous human diseases, standardized diets are also a prerequisite to conduct diet-disease interaction studies. We suggest that a comprehensive approach, which combines deep phenotyping with disease-related models under defined dietary conditions, might lead to the foundation of a so-called fly clinic.
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http://dx.doi.org/10.1186/s12263-019-0627-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6359822PMC
February 2019

Combination of Dietary Ahiflower Oil and Equol Enhances Long-Chain Polyunsaturated Fatty Acid Levels in Rainbow Trout Tissues.

Lipids 2018 11 5;53(11-12):1069-1083. Epub 2019 Feb 5.

GMA - Gesellschaft für Marine Aquakultur mbH, Hafentörn 3, 25761, Büsum, Germany.

Equol and Ahiflower oil have been shown to increase either eicosapentaenoic acid (EPA, 20:5n-3) or docosahexaenoic acid (DHA, 22:6n-3) levels in tissues of rainbow trout when applied individually. Thus, we investigated whether the combination of an Ahiflower oil-based diet and equol might increase both, EPA and DHA levels, in rainbow trout. Rainbow trout (87.1 ± 0.3 g) were fed with five diets for 8 weeks. A diet based on a blend of fish and vegetable oils (FV) served as a reference diet. The four experimental diets contained a blend of Ahiflower oil and vegetable oils (AV). The AV-diets were supplemented with equol by 0.0%, 0.1%, 0.2%, and 0.3% DM of the diet (AV-C, AV-EQ1, AV-EQ2, and AV-EQ3). The dietary treatments did not affect growth performance of fish and chemical nutrient composition of the whole body samples. Fish fed with the equol diets showed dose-dependently increased liver weights and 18:0 liver levels. The content of EPA showed no consistent pattern between tissues but all AV-groups were characterized by higher liver EPA values than FV. DHA values of AV-EQ2 and AV-EQ3 were similar to FV in fillet, tended to be the highest in the whole body and were significantly higher in liver compared to FV. In contrast, mRNA steady state levels of fatty acyl desaturase 2a (delta-6) [fads2a(d6)] were not affected by the dietary treatments. In conclusion, the combination of dietary Ahiflower oil and equol (0.2% and 0.3%) seems to affect the fatty acid metabolism of rainbow trout positively to increase DHA tissue levels.
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http://dx.doi.org/10.1002/lipd.12117DOI Listing
November 2018

Screening dietary biochanin A, daidzein, equol and genistein for their potential to increase DHA biosynthesis in rainbow trout (Oncorhynchus mykiss).

PLoS One 2019 15;14(1):e0210197. Epub 2019 Jan 15.

GMA-Gesellschaft für Marine Aquakultur mbH, Büsum, Germany.

Plant oil utilization in aquafeeds is still the most practical option, although it decreases the content of the nutritionally highly valuable omega-3 fatty acids eicosapentaenoic acid (20:5n-3, EPA) and docosahexaenoic acid (22:6n-3, DHA) in fish. Phytoestrogens and their metabolites are putatively able to affect genes encoding proteins centrally involved in the biosynthesis of EPA and DHA due to their estrogenic potential. Thus, the aim of the study was to screen the potential of the phytoestrogens to stimulate the biosynthesis of EPA and DHA in rainbow trout (Oncorhynchus mykiss). Additionally, the potential effects on growth performance, nutrient composition and hepatic lipid metabolism in rainbow trout were investigated. For that, a vegetable oil based diet served as a control diet (C) and was supplemented with 15 g/kg dry matter of biochanin A (BA), daidzein (DA), genistein (G) and equol (EQ), respectively. These five diets were fed to rainbow trout (initial body weight 83.3 ± 0.4 g) for 52 days. Growth performance and nutrient composition of whole body homogenates were not affected by the dietary treatments. Furthermore, feeding EQ to rainbow trout significantly increased DHA levels by +8% in whole body homogenates compared to samples of fish fed the diet C. A tendency towards increased DHA levels in whole body homogenates was found for fish fed the diet G. Fish fed diets BA and DA lacked these effects. Moreover, EQ and G fed fish showed significantly decreased hepatic mRNA steady state levels for fatty acyl desaturase 2a (delta-6) (fads2a(d6)). In contrast, carnitine palmitoyl transferases 1 (cpt1) hepatic mRNA steady state levels and hepatic Fads2a(d6) protein contents were not affected by the dietary treatment. In conclusion, when combined with dietary vegetable oils, equol and genistein seem to stimulate the biosynthesis of DHA and thereby increase tissue DHA levels in rainbow trout, however, only to a moderate extent.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0210197PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6333376PMC
September 2019

Dietary ursolic acid improves health span and life span in male Drosophila melanogaster.

Biofactors 2019 Mar 29;45(2):169-186. Epub 2018 Nov 29.

Institute of Human Nutrition and Food Science, University of Kiel, Kiel, Germany.

The health and life span of Drosophila melanogaster are partly determined by intestinal barrier integrity, metabolic rate as well as stress response and the expression of longevity-associated genes, depending on genetic and dietary factors. Ursolic acid (UA) is a naturally occurring triterpenoid exhibiting potential antimicrobial, anti-inflammatory, and antiobesity activity and counteracting age-related deficits in muscle strength. In this study, UA was dietarily administered to w D. melanogaster which significantly elongated the health and life span of males. Spargel (srl) is the Drosophila orthologue of mammalian peroxisome proliferator-activated receptor-gamma coactivator 1 α(PGC1α), an important regulator of energy homeostasis and mitochondrial function. Our results indicate that the health-promoting effect of UA, demonstrated by a significant increase in climbing activity, occurs via an upregulation of srl expression leading to a metabolic shift in the fly without reducing fecundity or gut integrity. Moreover, UA affected the flies' microbiota in a manner that contributed to life span extension. Srl expression and microbiota both seem to be affected by UA, as we determined by using srl-mutant and axenic flies. © 2018 BioFactors, 45(2):169-186, 2019.
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http://dx.doi.org/10.1002/biof.1467DOI Listing
March 2019

Resveratrol Modulates Desaturase Expression and Fatty Acid Composition of Cultured Hepatocytes.

Front Nutr 2018 14;5:106. Epub 2018 Nov 14.

Institute of Human Nutrition and Food Science, University of Kiel, Kiel, Germany.

This study aimed to evaluate whether resveratrol (RSV) and its microbial metabolites dihydro-resveratrol (DHR) and lunularin (LUN) affected fatty acid metabolism and omega-3 polyunsaturated fatty acid (n3-PUFA) synthesis in cultured hepatocytes. To this end, cultured human HepG2 hepatocytes were treated with non-toxic concentrations of these polyphenols (40 μM) and Δ and Δ ( and , respectively) expression was measured. Resveratrol induced both genes but DHR and LUN showed no effect. Co-incubation of RSV with α-linolenic acid (ALA) also induced and expression. Moreover, transcription of and expression was increased, indicating induction of β-oxidation and fatty acid synthesis, respectively. Using gas chromatography to measure fatty acid levels, we observed the impact of RSV with and without ALA treatment on fatty acid composition. However, RSV reduced unsaturated while increasing saturated fatty acid levels. We found lower amounts of monounsaturated fatty acids (16:1n-7c, 18:1n-9c, 18:1n7c, and 20:1n-9) and n3-PUFA docosahexaenoic acid whereas unsaturated fatty acid levels, especially of stearic acid, were elevated. Of interest, once we co-incubated the cells with RSV together with bovine serum albumin, we found no differences in gene expression compared to cells without RSV treatment. Although we found no positive effect of RSV on n3-PUFA synthesis, the stilbene could possibly prevent cellular stress by decreasing unsaturated fatty acid levels.
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http://dx.doi.org/10.3389/fnut.2018.00106DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6246710PMC
November 2018

Flavonoids as putative modulators of Δ4-, Δ5-, and Δ6-desaturases: Studies in cultured hepatocytes, myocytes, and adipocytes.

Biofactors 2018 Sep;44(5):485-495

Institute of Human Nutrition and Food Science, University of Kiel, Kiel, Germany.

This study was conducted to screen flavonoids for affecting expression of desaturases involved in omega-3 fatty acid synthesis and ceramide (CER) metabolism. To this end, cultured HepG2 hepatocytes, C2C12 myocytes, and 3T3-L1 adipocytes were treated with nontoxic concentrations of 12 selected flavonoids and expression of Δ4-, Δ5-, and Δ6-desaturases (DEGS1, FADS1, and FADS2, respectively) was determined. The flavonoids tested were more cytotoxic to HepG2 and 3T3-L1 than to C2C12 cells. In HepG2 cells, FADS1 was induced by quercetin and FADS2 expression was increased by daidzein, genistein, and pratensein treatment. DEGS1 was increased by apigenin, luteolin, orobol, and quercetin administration. In differentiated C2C12 cells, substances had no inducing effect or even lowered target gene expression. Pratensein induced both FADS1 and FADS2 in differentiated 3T3-L1 cells and DEGS1 was increased by treatment with apigenin, genistein, luteolin, orobol, and quercetin. In conclusion, pratensein may be an interesting test compound for further studies in vitro and in vivo on omega-3 synthesis since it induces its rate-limiting enzyme FADS2. Apigenin, luteolin, orobol, and quercetin induced DEGS1 and thereby possibly synthesis of proapoptotic CER in malignant HepG2 cells and 3T3-L1. In contrast, in benign C2C12 cells, they did not elevate mRNA steady state levels of DEGS1. That may partly explain the higher resistance of C2C12 cells against flavonoids compared to the other cell lines. By affecting tumor cells and nontumor cells differently, these flavonoids may be promising substances for further research regarding anticancer properties. © 2018 BioFactors, 44(5):485-495, 2018.
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http://dx.doi.org/10.1002/biof.1443DOI Listing
September 2018

Dietary Buglossoides arvensis Oil as a Potential Candidate to Substitute Fish Oil in Rainbow Trout Diets.

Lipids 2018 08 17;53(8):809-823. Epub 2018 Oct 17.

GMA-Gesellschaft für Marine Aquakultur mbH, Hafentörn 3, 25761, Büsum, Germany.

The utilization of vegetable oils in salmonid diets substantially decreased the body content of omega-3 long-chain polyunsaturated fatty acids (n-3 LC-PUFA), and thus the product quality for human consumption. Therefore, new ingredients for aquaculture feeds are needed that maximize the deposition of health-promoting n-3 LC-PUFA. This study investigated Buglossoides arvensis (Ahiflower) oil, a plant oil rich in alpha-linolenic acid (18:3n-3, ALA) and stearidonic acid (18:4n-3, SDA), as a source of n-3 fatty acids in rainbow trout (Oncorhynchus mykiss) nutrition. Rainbow trout (87.4 ± 0.6 g) were fed for 56 days. The oils of the control diet (FV) were substituted by Ahiflower oil at 33%, 66%, and 100% (A33, A66, A100). Dietary Ahiflower oil increased the final body weights of fish. mRNA steady state levels of fatty acyl desaturase 2a (delta-6) (fads2a(d6)) and 2b (delta-5) (fads2b(d5)) as well as carnitine palmitoyl transferase 1 a (cpt1a) were not altered by dietary treatments. In contrast, cpt1c mRNA steady state levels were significantly downregulated in samples of fish fed A66 and A100. Significantly higher eicosapentaenoic acid (20:5n-3, EPA) and docosahexaenoic acid (22:6n-3, DHA) levels were found in the liver and significantly higher EPA levels in the fillet of rainbow trout of A66 and A100 compared to FV. The content of DHA in fillets of fish fed Ahiflower oil was not significantly different to fish fed FV. Thus, high dietary amounts of Ahiflower oil can compensate for reduced dietary EPA and DHA levels.
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http://dx.doi.org/10.1002/lipd.12092DOI Listing
August 2018
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