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Institute
- Institut für Ernährungswissenschaft (1244) (remove)
Aging is associated with bone loss, which can lead to osteoporosis and high fracture risk. This coincides with the enhanced formation of bone marrow adipose tissue (BMAT), suggesting a negative effect of bone marrow adipocytes on skeletal health. Increased BMAT formation is also observed in pathologies such as obesity, type 2 diabetes and osteoporosis. However, a subset of bone marrow adipocytes forming the constitutive BMAT (cBMAT), arise early in life in the distal skeleton, contain high levels of unsaturated fatty acids and are thought to provide a physiological function. Regulated BMAT (rBMAT) forms during aging and obesity in proximal regions of the bone and contain a large proportion of saturated fatty acids. Paradoxically, BMAT accumulation is also enhanced during caloric restriction (CR), a life-span extending dietary intervention. This indicates, that different types of BMAT can form in response to opposing nutritional stimuli with potentially different functions.
To this end, two types of nutritional interventions, CR and high fat diet (HFD), that are both described to induce BMAT accumulation were carried out. CR markedly increased BMAT formation in the proximal tibia and led to a higher proportion of unsaturated fatty acids, making it similar to the physiological cBMAT. Additionally, proximal and diaphyseal tibia regions displayed higher adiponectin expression. In aged mice, CR was associated with an improved trabecular bone structure. Taken together, these findings demonstrate, that the type of BMAT that forms during CR might provide beneficial effects for local bone stem/progenitor cells and metabolic health. The HFD intervention performed in this thesis showed no effect on BMAT accumulation and bone microstructure. RNA Seq analysis revealed alterations in the composition of the collagen-containing extracellular matrix (ECM).
In order to investigate the effects of glucose homeostasis on osteogenesis, differentiation capacity of immortalized multipotent mesenchymal stromal cells (MSCs) and osteochondrogenic progenitor cells (OPCs) was analyzed. Insulin improved differentiation in both cell types, however, combination of with a high glucose concentration led to an impaired mineralization of the ECM. In the MSCs, this was accompanied by the formation of adipocytes, indicating negative effects of the adipocytes formed during hyperglycemic conditions on mineralization processes. However, the altered mineralization pattern and structure of the ECM was also observed in OPCs, which did not form any adipocytes, suggesting further negative effects of a hyperglycemic environment on osteogenic differentiation.
In summary, the work provided in this thesis demonstrated that differentiation commitment of bone-resident stem cells can be altered through nutrient availability, specifically glucose. Surprisingly, both high nutrient supply, e.g. the hyperglycemic cell culture conditions, and low nutrient supply, e.g. CR, can induce adipogenic differentiation. However, while CR-induced adipocyte formation was associated with improved trabecular bone structure, adipocyte formation in a hyperglycemic cell-culture environment hampered mineralization. This thesis provides further evidence for the existence of different types of BMAT with specific functions.
Purpose UK guidelines recommend dietary saturated fatty acids (SFAs) should not exceed 10% total energy (%TE) for cardiovascular disease prevention, with benefits observed when SFAs are replaced with unsaturated fatty acids (UFAs). This study aimed to assess the efficacy of a dietary exchange model using commercially available foods to replace SFAs with UFAs. Methods Healthy men (n = 109, age 48, SD 11 year) recruited to the Reading, Imperial, Surrey, Saturated fat Cholesterol Intervention-1 (RISSCI-1) study (ClinicalTrials.Gov n degrees NCT03270527) followed two sequential 4-week isoenergetic moderate-fat (34%TE) diets: high-SFA (18%TE SFAs, 16%TE UFAs) and low-SFA (10%TE SFAs, 24%TE UFAs). Dietary intakes were assessed using 4-day weighed diet diaries. Nutrient intakes were analysed using paired t-tests, fasting plasma phospholipid fatty acid (PL-FA) profiles and dietary patterns were analysed using orthogonal partial least square discriminant analyses. Results Participants exchanged 10.2%TE (SD 4.1) SFAs for 9.7%TE (SD 3.9) UFAs between the high and low-SFA diets, reaching target intakes with minimal effect on other nutrients or energy intakes. Analyses of dietary patterns confirmed successful incorporation of recommended foods from commercially available sources (e.g. dairy products, snacks, oils, and fats), without affecting participants' overall dietary intakes. Analyses of plasma PL-FAs indicated good compliance to the dietary intervention and foods of varying SFA content. Conclusions RISSCI-1 dietary exchange model successfully replaced dietary SFAs with UFAs in free-living healthy men using commercially available foods, and without altering their dietary patterns. Further intervention studies are required to confirm utility and feasibility of such food-based dietary fat replacement models at a population level.
The aim of this study was to assess the ability of the FFQ to describe reliable and valid dietary pattern (DP) scores. In a total of 134 participants of the European Prospective Investigation into Cancer and Nutrition-Potsdam study aged 35-67 years, the FFQ was applied twice (baseline and after 1 year) to assess its reliability. Between November 1995 and March 1997, twelve 24-h dietary recalls (24HDR) as reference instrument were applied to assess the validity of the FFQ. Exploratory DP were derived by principal component analyses. Investigated predefined DP were the Alternative Healthy Eating Index (AHEI) and two Mediterranean diet indices. From dietary data of each FFQ, two exploratory DP were retained, but differed in highly loading food groups, resulting in moderate correlations (r 0 center dot 45-0 center dot 58). The predefined indices showed higher correlations between the FFQ (r(AHEI) 0 center dot 62, r(Mediterranean Diet Pyramid Index (MedPyr)) 0 center dot 62 and r(traditional Mediterranean Diet Score (tMDS)) 0 center dot 51). From 24HDR dietary data, one exploratory DP retained differed in composition to the first FFQ-based DP, but showed similarities to the second DP, reflected by a good correlation (r 0 center dot 70). The predefined DP correlated moderately (r 0 center dot 40-0 center dot 60). To conclude, long-term analyses on exploratory DP should be interpreted with caution, due to only moderate reliability. The validity differed extensively for the two exploratory DP. The investigated predefined DP showed a better reliability and a moderate validity, comparable to other studies. Within the two Mediterranean diet indices, the MedPyr performed better than the tMDs in this middle-aged, semi-urban German study population.
The Caenorhabditis elegans (C. elegans) is a model organism that has been increasingly used in health and environmental toxicity assessments. The quantification of such elements in vivo can assist in studies that seek to relate the exposure concentration to possible biological effects.
Therefore, this study is the first to propose a method of quantitative analysis of 21 ions by ion chromatography (IC), which can be applied in different toxicity studies in C. elegans.
The developed method was validated for 12 anionic species (fluoride, acetate, chloride, nitrite, bromide, nitrate, sulfate, oxalate, molybdate, dichromate, phosphate, and perchlorate), and 9 cationic species (lithium, sodium, ammonium, thallium, potassium, magnesium, manganese, calcium, and barium).
The method did not present the presence of interfering species, with R2 varying between 0.9991 and 0.9999, with a linear range from 1 to 100 mu g L-1.
Limits of detection (LOD) and limits of quantification (LOQ) values ranged from 0.2319 mu g L-1 to 1.7160 mu g L-1 and 0.7028 mu g L-1 to 5.1999 mu g L-1, respectively.
The intraday and interday precision tests showed an Relative Standard Deviation (RSD) below 10.0 % and recovery ranging from 71.0 % to 118.0 % with a maximum RSD of 5.5 %.
The method was applied to real samples of C. elegans treated with 200 uM of thallium acetate solution, determining the uptake and bioaccumulated Tl+ content during acute exposure.
Epidemiological data suggest that consuming diets rich in carotenoids can reduce the risk of developing several non-communicable diseases. Thus, we investigated the extent to which carotenoid contents of foods can be increased by the choice of food matrices with naturally high carotenoid contents and thermal processing methods that maintain their stability. For this purpose, carotenoids of 15 carrot (Daucus carota L.) cultivars of different colors were assessed with UHPLC-DAD-ToF-MS. Additionally, the processing effects of air drying, air frying, and deep frying on carotenoid stability were applied. Cultivar selection accounted for up to 12.9-fold differences in total carotenoid content in differently colored carrots and a 2.2-fold difference between orange carrot cultivars. Air frying for 18 and 25 min and deep frying for 10 min led to a significant decrease in total carotenoid contents. TEAC assay of lipophilic extracts showed a correlation between carotenoid content and antioxidant capacity in untreated carrots.
Current attempts to prevent and manage type 2 diabetes have been moderately effective, and a better understanding of the molecular roots of this complex disease is important to develop more successful and precise treatment options.
Recently, we initiated the collective diabetes cross, where four mouse inbred strains differing in their diabetes susceptibility were crossed with the obese and diabetes-prone NZO strain and identified the quantitative trait loci (QTL) Nidd13/NZO, a genomic region on chromosome 13 that correlates with hyperglycemia in NZO allele carriers compared to B6 controls.
Subsequent analysis of the critical region, harboring 644 genes, included expression studies in pancreatic islets of congenic Nidd13/NZO mice, integration of single-cell data from parental NZO and B6 islets as well as haplotype analysis.
Finally, of the five genes (Acot12, S100z, Ankrd55, Rnf180, and Iqgap2) within the polymorphic haplotype block that are differently expressed in islets of B6 compared to NZO mice, we identified the calcium-binding protein S100z gene to affect islet cell proliferation as well as apoptosis when overexpressed in MINE cells. In summary, we define S100z as the most striking gene to be causal for the diabetes QTL Nidd13/NZO by affecting beta-cell proliferation and apoptosis. Thus, S100z is an entirely novel diabetes gene regulating islet cell function.
With the many challenges facing the agricultural system, such as water scarcity, loss of arable land due to climate change, population growth, urbanization or trade disruptions, new agri-food systems are needed to ensure food security in the future. In addition, healthy diets are needed to combat non-communicable diseases. Therefore, plant-based diets rich in health-promoting plant secondary metabolites are desirable. A saline indoor farming system is representing a sustainable and resilient new agrifood system and can preserve valuable fresh water. Since indoor farming relies on artificial lighting, assessment of lighting conditions is essential. In this thesis, the cultivation of halophytes in a saline indoor farming system was evaluated and the influence of cultivation conditions were assessed in favor of improving the nutritional quality of halophytes for human consumption. Therefore, five selected edible halophyte species (Brassica oleracea var. palmifolia, Cochlearia officinalis, Atriplex hortensis, Chenopodium quinoa, and Salicornia europaea) were cultivated in saline indoor farming. The halophyte species were selected for to their salt tolerance levels and mechanisms. First, the suitability of halophytes for saline indoor farming and the influence of salinity on their nutritional properties, e.g. plant secondary metabolites and minerals, were investigated. Changes in plant performance and nutritional properties were observed as a function of salinity. The response to salinity was found to be species-specific and related to the salt tolerance mechanism of the halophytes. At their optimal salinity levels, the halophytes showed improved carotenoid content. In addition, a negative correlation was found between the nitrate and chloride content of halophytes as a function of salinity. Since chloride and nitrate can be antinutrient compounds, depending on their content, monitoring is essential, especially in halophytes. Second, regional brine water was introduced as an alternative saline water resource in the saline indoor farming system. Brine water was shown to be feasible for saline indoor farming
of halophytes, as there was no adverse effect on growth or nutritional properties, e.g. carotenoids. Carotenoids were shown to be less affected by salt composition than by salt concentration. In addition, the interaction between the salinity and the light regime in indoor farming and greenhouse cultivation has been studied. There it was shown that interacting light regime and salinity alters the content of carotenoids and chlorophylls. Further, glucosinolate and nitrate content were also shown to be influenced by light regime. Finally, the influence of UVB light on halophytes was investigated using supplemental narrow-band UVB LEDs. It was shown that UVB light affects the growth, phenotype and metabolite profile of halophytes and that the UVB response is species specific. Furthermore, a modulation of carotenoid content in S. europaea could be achieved to enhance health-promoting properties and thus improve nutritional quality. This was shown to be dose-dependent and the underlying mechanisms of carotenoid accumulation were also investigated. Here it was revealed that carotenoid accumulation is related to oxidative stress.
In conclusion, this work demonstrated the potential of halophytes as alternative vegetables produced in a saline indoor farming system for future diets that could contribute to ensuring food security in the future. To improve the sustainability of the saline indoor farming system, LED lamps and regional brine water could be integrated into the system. Since the nutritional properties have been shown to be influenced by salt, light regime and UVB light, these abiotic stressors must be taken into account when considering halophytes as alternative vegetables for human nutrition.
Scaling agriculture to the globally rising population demands new approaches for future crop production such as multilayer and multitrophic indoor farming. Moreover, there is a current trend towards sustainable local solutions for aquaculture and saline agriculture. In this context, halophytes are becoming increasingly important for research and the food industry. As Salicornia europaea is a highly salt-tolerant obligate halophyte that can be used as a food crop, indoor cultivation with saline water is of particular interest. Therefore, finding a sustainable alternative to the use of seawater in non-coastal regions is crucial. Our goal was to determine whether natural brines, which are widely distributed and often available in inland areas, provide an alternative water source for the cultivation of saline organisms. This case study investigated the potential use of natural brines for the production of S. europaea. In the control group, which reflects the optimal growth conditions, fresh weight was increased, but there was no significant difference between the treatment groups comparing natural brines with artificial sea water. A similar pattern was observed for carotenoids and chlorophylls. Individual components showed significant differences. However, within treatments, there were mostly no changes. In summary, we showed that the influence of the different chloride concentrations was higher than the salt composition. Moreover, nutrient-enriched natural brine was demonstrated to be a suitable alternative for cultivation of S. europaea in terms of yield and nutritional quality. Thus, the present study provides the first evidence for the future potential of natural brine waters for the further development of aquaculture systems and saline agriculture in inland regions.
Insulin is the main anabolic hormone secreted by 13-cells of the pancreas stimulating the assimilation and storage of glucose in muscle and fat cells. It modulates the postprandial balance of carbohydrates, lipids and proteins via enhancing lipogenesis, glycogen and protein synthesis and suppressing glucose generation and its release from the liver. Resistance to insulin is a severe metabolic disorder related to a diminished response of peripheral tissues to the insulin action and signaling. This leads to a disturbed glucose homeostasis that precedes the onset of type 2 diabetes (T2D), a disease reaching epidemic proportions. A large number of studies reported an association between elevated circulating fatty acids and the development of insulin resistance. The increased fatty acid lipid flux results in the accumulation of lipid droplets in a variety of tissues. However, lipid intermediates such as diacylglycerols and ceramides are also formed in response to elevated fatty acid levels. These bioactive lipids have been associated with the pathogenesis of insulin resistance. More recently, sphingosine 1-phosphate (S1P), another bioactive sphingolipid derivative, has also been shown to increase in T2D and obesity. Although many studies propose a protective role of S1P metabolism on insulin signaling in peripheral tissues, other studies suggest a causal role of S1P on insulin resistance. In this review, we critically summarize the current state of knowledge of S1P metabolism and its modulating role on insulin resistance. A particular emphasis is placed on S1P and insulin signaling in hepatocytes, skeletal muscle cells, adipocytes and pancreatic 13-cells. In particular, modulation of receptors and enzymes that regulate S1P metabolism can be considered as a new therapeutic option for the treatment of insulin resistance and T2D.