Body composition and metabolism associated with genetic factors, nutrition and metabolomics data in adults

The human health status is co-determined by the interplay of body composition, metabolism, and energy balance. In turn, these factors are influenced by genetic predispositions, a multitude of environmental factors such as nutritional habits or physical activity, and interactive effects between these parameters. Malnutrition and obesity reflect extreme phenotypes of body composition, and lead to disturbances in metabolism. Especially obesity as a prominent health problem in industrialised countries is linked to an increased risk of morbidity and mortality. Important regulators of energy balance and metabolism are thyroid hormones and disturbances of their homoeostasis are associated with serious health problems. Metabolomics is an evolving field which has the ability to represent a snapshot of the current metabolic state. Disturbances of pathways can be captured and the utilisation of closely connected metabolites ratios provides proxies for enzymatic reactions. In this doctoral thesis, three projects are presented exploring the interplay of body composition,metabolism, and energy homeostasis by focusing on gene–nutrition interactions and their effect on obesity risk, the relationship between fat free mass and the serum metabolite profile of adults, and the influence of thyroid hormones on the metabolism in euthyroid adult participants. The first project aims at improving the understanding of inter-individual variance and susceptibility towards obesity. Common obesity is the result of a genetic predisposition in combination with nowadays modern environment which encourages a sedentary lifestyle and often leads to an imbalance in energy intake and expenditure, subsequently followed by weight gain. To this end, adjusted logistic regression models are used to analyse the interaction effects between single nucleotide polymorphisms (SNPs) of different candidate genes for obesity and polyunsaturated fatty acids (PUFAs) analysed in erythrocyte membranes, which are valid biomarkers for PUFA intake, on the obesity risk in adults participating in a crosssectional population-based study. Several significant SNP–PUFA interactions are identified, indicating regulatory effects of PUFAs by gene variants of interleukin (IL)-2, IL-6, IL-18,tumour necrosis factor receptor superfamily (TNFRSF) member 1B and 21, leptin receptor (LEPR), and adiponectin (ADIPOQ). Due to the limited statistical power of this study, these results have to be reproduced in a sufficiently sized prospective study. If replicated, our results would indicate a beneficial effect of high PUFA supply for a substantial proportion of the population with respect to obesity risk. Aspiration of the second project is to provide a comprehensive picture of fat free mass induced effects on the metabolite profile in blood samples of adults. Further, it is hypothesised that a sedentary lifestyle leads to derangements in skeletal muscle metabolism, e.g., favouring the development of obesity. Thus, the associations between the fat free mass index (FFMI) and up to 190 serum metabolite concentrations - with a focus on amino acids, acylcarnitines, phosphatidylcholines (PCs), and sphingomyelins - and all intra-class metabolite ratios are investigated by means of adjusted linear regression models in cross-sectional analyses of a cohort study. These analyses reveal 339 significant associations between FFMI and various metabolites and metabolite ratios. Among the most prominent associations with higher FFMI are increasing concentrations of the branched-chain amino acids (BCAAs), ratios of BCAAs to glucogenic amino acids, and carnitine concentrations. These findings are in agreement with the expected metabolic situation in fasted participants. Most of these results are replicated in the follow-up survey of the analysed baseline study. In order to draw a comprehensive picture of the FFMI effects, Gaussian graphical models (GGMs) are computed. These models have previously been shown to reveal the true relationships among metabolites. Further, genetic aspects are investigated. To this end, the relationships between SNPs described to be associated with anthropometric characteristics and the metabolite variables are analysed; however, no significant association is revealed. Sensitivity and stratified analyses are carefully performed. Most interestingly, almost all associations which are found for the entire sample are largely missing in the obese subgroup supporting our hypothesis that the accumulation of body fat tissue may be accompanied by a derangement in skeletal muscle metabolism. The aim of the third project is to identify thyroid hormone related changes on metabolism of fasting euthyroid participants in a cross-sectional analysis of a cohort study. To this end, the associations between free tyroxine (FT4), thyrotropin (TSH), and 151 metabolites as well as their pairwise intra-class metabolite ratios are analysed in adjusted linear regression models. Increased serum FT4 levels are associated with an overall enhanced transport to the mitochondria and beta-oxidation of fatty acids which is reflected by significantly increased serum acylcarnitine concentrations and decreased PC concentrations. Further, these findings are largely stable as they could be reproduced in different subsets of the population, including obese versus non-obese participants. No significant associations are found between the metabolite variables and the TSH concentrations. In summary, this doctoral thesis provides indication of a beneficial effect of high PUFA supply for specific genotype carriers with respect to obesity risk. An extensive image of FFMI effects in a data-driven metabolic network is revealed and high body fat accumulation is linked to a derangement in skeletal muscle metabolism. Further, this thesis broadens our knowledge of FT4 triggered pathways in euthyroid participants. Thus, this thesis contributes deeper insight into the interplay of body composition, metabolism, and energy balance.Der Gesundheitszustand des Menschen wird neben anderen Faktoren durch das Zusammenspiel von Körperzusammensetzung, Stoffwechsel und Energiehaushalt bestimmt. Diese Faktoren werden wiederum durch genetische Prädispositionen, eine Vielzahl von Umweltfaktoren, wie beispielsweise Ernährungsgewohnheiten oder körperliche Aktivität, sowie durch Interaktionseffekte dieser Parameter beeinflusst. Unterernährung und Adipositas reflektieren extreme Phänotypen der Körperzusammensetzung und führen zu Störungen im Stoffwechsel. Insbesondere Adipositas, ein prominentes Gesundheitsproblem in den industrialisierten Ländern, erhöht das Morbiditäts- und Mortalitätsrisiko. Der Energiehaushalt und der Stoffwechsel unterliegen einem starken Einfluss der Schilddrüsenhormone. Störungen ihrer Homöostase sind mit schweren gesundheitlichen Problemen verbunden. Die Metabolomforschung (englisch “metabolomics”) ist ein sich entwickelndes Forschungsgebiet, welches es an Hand der gemessenen Metaboliten ermöglicht, eine Momentaufnahme der aktuellen Stoffwechsellage abzuzeichnen. Darüber hinaus bietet die Untersuchung der Metaboliten die Möglichkeit, Störungen in Stoffwechselwegen zu erfassen und durch die Verwendung von Metaboliten-Quotienten enzymatische Reaktionen zu identifizieren. In dieser Dissertation werden drei Projekte vorgestellt, welche das Zusammenspiel von Körperzusammensetzung, Stoffwechsel und Energiehaushalt erforschen. Die Schwerpunkte liegen dabei auf Gen–Ernährungs–Interaktionen und ihre Auswirkungen auf das Adipositasrisiko, auf der Beziehung zwischen der fettfreien Masse und den Serum–Metaboliten–Profilen Erwachsener, sowie auf dem Einfluss der Schilddrüsenhormone auf den Stoffwechsel; letzterer widergespiegelt in den Serum–Metaboliten–Profilen euthyroider erwachsener Studienteilnehmer. Das erste Projekt zielt darauf ab, das Verständnis der inter-individuellen Variabilität und Empfänglichkeit gegenüber Adipositas zu verbessern. Adipositas ist das Ergebnis einer genetischen Prädisposition in Kombination mit dem heutigen modernen Lebensumfeld. Dieses ist oft geprägt von einer sitzenden Lebensweise und führt dadurch zu einem Ungleichgewicht in Energieaufnahme und -verbrauch, welches letztendlich mit einer Gewichtszunahme verbunden ist. Bezüglich des Adipositasrisikos bei Erwachsenen werden die Wechselwirkungen zwischen Einzelnukleotid-Polymorphismen (SNPs) unterschiedlicher Adipositas-Kandidatengene und der Erythrozytenmembranzusammensetzung mehrfach ungesättigter Fettsäuren (PUFAs), welche valide Biomarker für die PUFA–Zufuhr darstellen, mit Hilfe von adjustierten logistischen Regressionsmodellen in einer populationsbasierten Querschnittsstudie untersucht. Mehrere signifikante SNP-PUFA-Interaktionen werden gefunden, die auf einen regulatorischen Effekt der PUFA auf Genvarianten von Interleukin (IL)-2, IL-6, IL-18,Tumornekrosefaktor-Rezeptor-Superfamilie (TNFRSF) Element 1B und 21, Leptin–Rezeptor (LEPR) und Adiponektin (ADIPOQ) hinweisen. Aufgrund der begrenzten statistischen Teststärke dieser Studie sollten diese Ergebnisse in einer ausreichend großen prospektiven Studie repliziert werden. Bei Bestätigung der hier dargestellten Ergebnisse, würden diese eine positive Wirkung einer hohen PUFA-Versorgung für einen erheblichen Anteil der Bevölkerung im Hinblick auf das Adipositasrisiko anzeigen. Im zweiten Projekt soll ein umfassendes Bild der durch die fettfreie Masse (als Proxy für die Muskelmasse) induzierten Effekte auf das Stoffwechselprofil in Blutproben von Erwachsenen ermittelt werden. Ebenso soll die Hypothese geklärt werden, ob eine sitzende Lebensweise zu Störungen des Skelettmuskulatur–Stoffwechsels führen kann, welche z.B. die Entwicklung von Adipositas begünstigen könnten. Dazu werden die Assoziationen zwischen dem fettfreien Masse Index (FFMI) und bis zu 190 Serummetaboliten (unter anderem Aminosäuren, Acylcarnitine, Phosphatidylcholine (PCs) und Sphingomyeline) sowie der paarweisen Metaboliten-Quotienten innerhalb der einzelnen Klassen mit Hilfe von adjustierten linearen Modellen in unabhängigen Querschnittsauswertungen einer Kohortenstudie untersucht. Es werden 339 signifikante Assoziationen zwischen FFMI und den verschiedenen Metaboliten und Metaboliten-Quotienten gefunden. Zu den prominentesten Assoziationen mit höherem FFMI gehören steigende Konzentrationen der verzweigtkettigen Aminosäuren (BCAA), Assoziationen mit Quotienten von BCAAs zu glukogenen Aminosäuren und mit verschiedenen Carnitin-Konzentrationen. Diese Ergebnisse stimmen mit den Erwartungen bezüglich des Stoffwechsels nüchterner Personen überein. Die meisten dieser Ergebnisse werden auch im Follow-Up der analysierten Studie repliziert. Um ein umfassendes Bild der FFMI-Effekte aufzuzeigen, werden Gauß’sche graphische Modelle (GGMs) gerechnet. Vor kurzem wurde gezeigt, dass diese Modelle die wahren Beziehungen zwischen einzelnen Metaboliten offenlegen können. In diesem Projekt werden ebenfalls genetische Aspekte berücksichtigt. Dazu werden die Assoziationen zwischen SNPs, für die ein Zusammenhang mit anthropometrischen Merkmalen beschrieben wurde, und den Metabolitenvariablen untersucht. Jedoch werden keine signifikanten Assoziationen gefunden. Sensitivitätsanalysen und stratifizierte Analysen werden sorgfältig realisiert. Interessanterweise fehlen fast alle Assoziationen, die für die gesamte Population vorhanden sind, in der adipösen Untergruppe. Dieses Ergebnis unterstützt unsere Hypothese, dass eine Akkumulation von Fettgewebe möglicherweise mit einer Störung im Skelettmuskulatur–Stoffwechsel einhergeht. Die Zielsetzung des dritten Projektes ist es, die Auswirkungen der Schilddrüsenhormone auf den Stoffwechsel bei nüchternen euthyroiden Teilnehmern einer Kohortenstudie in einer unabhängigen Querschnittsauswertung zu analysieren. Zu diesem Zweck werden die Assoziationen zwischen freiem Tyroxin (FT4), Thyreotropin (TSH), und 151 Metaboliten sowie der paarweisen Metaboliten-Quotienten innerhalb der einzelnen Klassen mittels adjustierter linearer Modelle untersucht. Eine erhöhte Serumkonzentration des FT4 ist mit einem insgesamt verbesserten Transport in die Mitochondrien und einer gesteigerten beta-Oxidation der Fettsäuren verbunden, welche durch signifikant erhöhte Serum–Konzentrationen von Acylcarnitinen und verringerte Konzentrationen von PCs angezeigt wird. Diese Ergebnisse sind weitgehend stabil, da sie in verschiedenen Subgruppen, unter anderem in adipösen versus nicht-adipösen Studienteinehmern, reproduziert werden können. Zwischen den TSH–Konzentrationen und den Serum–Metaboliten-Profilen sind keine signifikanten Beziehungen gefunden worden. Zusammenfassend liefert diese Dissertation Hinweise auf einen positiven Effekt einer erhöhten PUFA–Versorgung für spezifische Genotyp–Träger mit Bezug auf das Adipositasrisiko. Sie zeigt ein umfangreiches Bild der FFMI–Effekte auf den Stoffwechsel in einem datengesteuerten Netzwerk auf und gibt Hinweise darauf, dass eine hohe Körperfettakkumulation mit einer Störung des Skelettmuskulatur-Stoffwechsels verbunden ist. Darüber hinaus wird unser Wissen über FT4–gesteuerte Stoffwechselwege in euthyroiden Personen erweitert. Somit gewährt diese Arbeit einen tieferen Einblick in das Zusammenspiel von Körperzusammensetzung, Stoffwechsel und Energiehaushalt

Treatment of thyroid dysfunctions decreases the risk of cerebrovascular events in men but not in women: results of the MONICA/KORA Cohort Study

OBJECTIVE:Thyroid disorders are well known to be associated with cardiovascular diseases. Some studies have shown that the negative effects of thyroid disorders are partially reversible after adequate treatment. The aim of this analysis was to assess the risk of incident ischemic cerebrovascular diseases in study participants treated for thyroid dysfunctions in a population-based cohort study. METHODS:For the presented analyses data from 8564 male and 8714 female individuals aged 25 to 74 years of the MONICA/KORA cohort were used (median follow-up 14.0 years). A combined binary variable "thyroid disorder" (TDC) was created utilizing data on self-reported physician-treated thyroid disorders and information about medication use. To examine the association between TDC and incident ischemic cerebrovascular events, we performed multiple adjusted Cox proportional hazard regression models and calculated hazard ratios and corresponding 95% confidence intervals (HR, 95%CI). RESULTS:During follow-up between 1984 and 2008/2009, 514 incident fatal and non-fatal ischemic cerebrovascular events occurred in men and 323 in women. At baseline, 3.5% of men and 15.6% of women reported TDC. In the fully adjusted model, males who reported TDC had a significantly reduced risk of ischemic cerebrovascular events (HR = 0.52, 95%CI = 0.29-0.92). A similar result was obtained in men, when we utilized information on thyroid hormones use only. For the total study population and for women with TDC we found no association with ischemic cerebrovascular events. CONCLUSIONS:In our longitudinal analyses subjects with treated thyroid diseases had no increased risk of incident ischemic cerebrovascular events. Surprisingly in males, even a significantly reduced risk of incident ischemic cerebrovascular events was found, a result that deserves further clarification

Multi-omic signature of body weight change: results from a population-based cohort study

BACKGROUND: Excess body weight is a major risk factor for cardiometabolic diseases. The complex molecular mechanisms of body weight change-induced metabolic perturbations are not fully understood. Specifically, in-depth molecular characterization of long-term body weight change in the general population is lacking. Here, we pursued a multi-omic approach to comprehensively study metabolic consequences of body weight change during a seven-year follow-up in a large prospective study. METHODS: We used data from the population-based Cooperative Health Research in the Region of Augsburg (KORA) S4/F4 cohort. At follow-up (F4), two-platform serum metabolomics and whole blood gene expression measurements were obtained for 1,631 and 689 participants, respectively. Using weighted correlation network analysis, omics data were clustered into modules of closely connected molecules, followed by the formation of a partial correlation network from the modules. Association of the omics modules with previous annual percentage weight change was then determined using linear models. In addition, we performed pathway enrichment analyses, stability analyses, and assessed the relation of the omics modules with clinical traits. RESULTS: Four metabolite and two gene expression modules were significantly and stably associated with body weight change (P-values ranging from 1.9 × 10−4 to 1.2 × 10−24). The four metabolite modules covered major branches of metabolism, with VLDL, LDL and large HDL subclasses, triglycerides, branched-chain amino acids and markers of energy metabolism among the main representative molecules. One gene expression module suggests a role of weight change in red blood cell development. The other gene expression module largely overlaps with the lipid-leukocyte (LL) module previously reported to interact with serum metabolites, for which we identify additional co-expressed genes. The omics modules were interrelated and showed cross-sectional associations with clinical traits. Moreover, weight gain and weight loss showed largely opposing associations with the omics modules. CONCLUSIONS: Long-term weight change in the general population globally associates with serum metabolite concentrations. An integrated metabolomics and transcriptomics approach improved the understanding of molecular mechanisms underlying the association of weight gain with changes in lipid and amino acid metabolism, insulin sensitivity, mitochondrial function as well as blood cell development and function

Body Fat Free Mass Is Associated with the Serum Metabolite Profile in a Population-Based Study

To characterise the influence of the fat free mass on the metabolite profile in serum samples from participants of the population-based KORA (Cooperative Health Research in the Region of Augsburg) S4 study. Analyses were based on metabolite profile from 965 participants of the S4 and 890 weight-stable subjects of its seven-year follow-up study (KORA F4). 190 different serum metabolites were quantified in a targeted approach including amino acids, acylcarnitines, phosphatidylcholines (PCs), sphingomyelins and hexose. Associations between metabolite concentrations and the fat free mass index (FFMI) were analysed using adjusted linear regression models. To draw conclusions on enzymatic reactions, intra-metabolite class ratios were explored. Pairwise relationships among metabolites were investigated and illustrated by means of Gaussian graphical models (GGMs). We found 339 significant associations between FFMI and various metabolites in KORA S4. Among the most prominent associations (p-values 4.75 × 10(-16)-8.95 × 10(-06)) with higher FFMI were increasing concentrations of the branched chained amino acids (BCAAs), ratios of BCAAs to glucogenic amino acids, and carnitine concentrations. For various PCs, a decrease in chain length or in saturation of the fatty acid moieties could be observed with increasing FFMI, as well as an overall shift from acyl-alkyl PCs to diacyl PCs. These findings were reproduced in KORA F4. The established GGMs supported the regression results and provided a comprehensive picture of the relationships between metabolites. In a sub-analysis, most of the discovered associations did not exist in obese subjects in contrast to non-obese subjects, possibly indicating derangements in skeletal muscle metabolism. A set of serum metabolites strongly associated with FFMI was identified and a network explaining the relationships among metabolites was established. These results offer a novel and more complete picture of the FFMI effects on serum metabolites in a data-driven network

Does personality affect premating isolation between locally-adapted populations?

Background: One aspect of premating isolation between diverging, locally-adapted population pairs is female mate choice for resident over alien male phenotypes. Mating preferences often show considerable individual variation, and whether or not certain individuals are more likely to contribute to population interbreeding remains to be studied. In the Poecilia mexicana-species complex different ecotypes have adapted to hydrogen sulfide (H2S)-toxic springs, and females from adjacent non-sulfidic habitats prefer resident over sulfide-adapted males. We asked if consistent individual differences in behavioral tendencies (animal personality) predict the strength and direction of the mate choice component of premating isolation in this system. Results: We characterized focal females for their personality and found behavioral measures of ‘novel object exploration’, ‘boldness’ and ‘activity in an unknown area’ to be highly repeatable. Furthermore, the interaction term between our measures of exploration and boldness affected focal females’ strength of preference (SOP) for the resident male phenotype in dichotomous association preference tests. High exploration tendencies were coupled with stronger SOPs for resident over alien mating partners in bold, but not shy, females. Shy and/or little explorative females had an increased likelihood of preferring the non-resident phenotype and thus, are more likely to contribute to rare population hybridization. When we offered large vs. small conspecific stimulus males instead, less explorative females showed stronger preferences for large male body size. However, this effect disappeared when the size difference between the stimulus males was small. Conclusions: Our results suggest that personality affects female mate choice in a very nuanced fashion. Hence, population differences in the distribution of personality types could be facilitating or impeding reproductive isolation between diverging populations depending on the study system and the male trait(s) upon which females base their mating decisions, respectively

Monitoreo de servicios ecosistémicos en un observatorio de cafetales agroforestales. Recomendaciones para el sector cafetalero

Ocho años de estudio de la ecofisiología del café, a través de experimentación y de modelación y el monitoreo de los servicios del ecosistema (SE) en una gran finca cafetalera en Costa Rica, revelaron varias recomendaciones prácticas para los agricultores y los formuladores de políticas. El sistema de cultivo estudiado dentro de nuestro observatorio colaborativo (Coffee-Flux), corresponde a un sistema agroforestal (SAF) a base de café bajo la sombra de grandes árboles de Erythrina poeppigiana (16% de la cubierta del dosel). Una gran cantidad de SE y limitantes dependen de las propiedades locales del suelo (en este caso Andisoles), especialmente de la erosión/infiltración, el agua/carbono y la capacidad de almacenamiento de nutrientes. Por lo tanto, para la evaluación de SE, el tipo de suelo es crucial. Una densidad adecuada de árboles de sombra (bastante baja aquí por la condición de libre crecimiento), redujo la severidad de las enfermedades de las hojas con la posibilidad de reducir el uso de plaguicidas y fungicidas. Un inventario simple del área basal en el collar de las plantas de café permitió estimar la biomasa subterránea y la edad promedio de la plantación, para juzgar su valor de mercado y decidir cuándo reemplazarla. Las fincas de café probablemente estén mucho más cerca de la neutralidad de C que lo indicado en el protocolo actual de C-neutralidad, que solo considera árboles de sombra, no los cafetos ni el suelo. Se proponen evaluaciones más completas, que ncluyen árboles, café, hojarasca, suelo y raíces en el balance C del SAF. Los árboles de sombra ofrecen muchos SE si se gestionan adecuadamente en el contexto local. En comparación con las condiciones a pleno sol, los árboles de sombra pueden (i) reducir la erosión laminar en un factor de 2; (ii) aumentar la fijación de N y el % de N reciclado en el sistema, reduciendo así los requisitos de fertilizantes; (iii) reducir la severidad de enfermedades de las hojas; (iv) aumentar el secuestro de C; (v) mejorar el microclima y (vi) reducir sustancialmente los efectos del cambio climático. En nuestro estudio de caso, no se encontró ningún efecto negativo sobre el rendimiento del café

Natural variation in social conditions affects male mate choosiness in the amphipod Gammarus roeselii

The extent of male mate choosiness is driven by a trade-off between various environmental factors associated with the costs of mate acquisition, quality assessment and opportunity costs. Our knowledge about natural variation in male mate choosiness across different populations of the same species, however, remains limited. In this study, we compared male mate choosiness across 10 natural populations of the freshwater amphipod Gammarus roeselii (Gervais 1835), a species with overall high male mating investments, and evaluated the relative influence of population density and sex ratio (both affecting mate availability) on male mate choosiness. We investigated amplexus establishment after separating mating pairs and presenting focal males with a novel, size-matched female from the same population. Our analysis revealed considerable effects of sex ratio and (to a lesser extent) population density on time until amplexus establishment (choosiness). Male amphipods are able to perceive variable social conditions (e.g., sex ratio) and modify their mating strategy accordingly: We found choosiness to be reduced in increasingly male-biased populations, whereas selectivity increases when sex ratio becomes female biased. With this, our study expands our limited knowledge on natural variations in male mate choosiness and illustrates the importance of sex ratio (i.e., level of competition) for male mating decisions in natural environments. Accounting for variation in sex ratios, therefore, allows envisioning a distinctive variation of choosiness in natural populations and highlights the importance of considering social background information in future behavioral studies

Usual dietary intake estimation based on a combination of repeated 24-H food lists and a food frequency questionnaire in the KORA FF4 cross-sectional study

Background: Estimation of usual dietary intake poses a challenge in epidemiological studies. We applied a blended approach that combines the strengths provided by repeated 24-h food lists (24HFLs) and a food frequency questionnaire (FFQ). Methods: At least two web-based 24HFLs and one FFQ were completed by 821 participants in the KORA FF4 study. Consumption probabilities were estimated using logistic mixed models, adjusting for covariates and the FFQ data on consumption frequency. Intake amount of a consumed food item was predicted for each participant based on the results of the second Bavarian Food Consumption Survey (BVS II). By combining consumption probability and estimated consumption amount, the usual food intake for each participant was estimated. These results were compared to results obtained without considering FFQ information for consumption probability estimation, as well as to conventional FFQ data. Results: The results of the blended approach for food group intake were often higher than the FFQ-based results. Intraclass correlation coefficients between both methods ranged between 0.21 and 0.86. Comparison of both methods resulted in weighted kappa values based on quintiles ranging from fair (0.34) to excellent agreement (0.84). Omission of FFQ information in the consumption probability models distinctly affected the results at the group level, though individual intake data were slightly affected, for the most part. Conclusions: Usual dietary intake data based on the blended approach differs from the FFQ-based results both in absolute terms and in classification according to quintiles. The application of the blended approach has been demonstrated as a possible tool in nutritional epidemiology, as a comparison with published studies showed that the blended approach yields reasonable estimates. The inclusion of the FFQ information is valuable especially with regard to irregularly consumed foods. A validation study including biomarkers of dietary intake is warranted

Associations between thyroid hormones and serum metabolite profiles in an euthyroid population

The aim was to characterise associations between circulating thyroid hormones—free thyroxine (FT4) and thyrotropin (TSH)—and the metabolite profiles in serum samples from participants of the German population-based KORA F4 study. Analyses were based on the metabolite profile of 1463 euthyroid subjects. In serum samples, obtained after overnight fasting (≥8), 151 different metabolites were quantified in a targeted approach including amino acids, acylcarnitines (ACs), and phosphatidylcholines (PCs). Associations between metabolites and thyroid hormone concentrations were analysed using adjusted linear regression models. To draw conclusions on thyroid hormone related pathways, intra-class metabolite ratios were additionally explored. We discovered 154 significant associations (Bonferroni p < 1.75 × 10(−04)) between FT4 and various metabolites and metabolite ratios belonging to AC and PC groups. Significant associations with TSH were lacking. High FT4 levels were associated with increased concentrations of many ACs and various sums of ACs of different chain length, and the ratio of C2 by C0. The inverse associations observed between FT4 and many serum PCs reflected the general decrease in PC concentrations. Similar results were found in subgroup analyses, e.g., in weight-stable subjects or in obese subjects. Further, results were independent of different parameters for liver or kidney function, or inflammation, which supports the notion of an independent FT4 effect. In fasting euthyroid adults, higher serum FT4 levels are associated with increased serum AC concentrations and an increased ratio of C2 by C0 which is indicative of an overall enhanced fatty acyl mitochondrial transport and β-oxidation of fatty acids. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s11306-013-0563-4) contains supplementary material, which is available to authorized users

Demographic, lifestyle and clinical factors by treated thyroid disorders (TDC) in men and women, KORA population S1-S4.

<p>Demographic, lifestyle and clinical factors by treated thyroid disorders (TDC) in men and women, KORA population S1-S4.</p