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Lundstedt-Enkel, Katrin
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Publications (10 of 34) Show all publications
Dhillon, S. S., Torell, F., Donten, M., Lundstedt-Enkel, K., Bennett, K., Raennar, S., . . . Lundstedt, T. (2019). Metabolic profiling of zebrafish embryo development from blastula period to early larval stages. PLoS ONE, 14(5), Article ID e0213661.
Open this publication in new window or tab >>Metabolic profiling of zebrafish embryo development from blastula period to early larval stages
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2019 (English)In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 14, no 5, article id e0213661Article in journal (Refereed) Published
Abstract [en]

The zebrafish embryo is a popular model for drug screening, disease modelling and molecular genetics. In this study, samples were obtained from zebrafish at different developmental stages. The stages that were chosen were 3/4, 4/5, 24, 48, 72 and 96 hours post fertilization (hpf). Each sample included fifty embryos. The samples were analysed using gas chromatography time-of-flight mass spectrometry (GC-TOF-MS). Principle component analysis (PCA) was applied to get an overview of the data and orthogonal projection to latent structure discriminant analysis (OPLS-DA) was utilised to discriminate between the developmental stages. In this way, changes in metabolite profiles during vertebrate development could be identified. Using a GC-TOF-MS metabolomics approach it was found that nucleotides and metabolic fuel (glucose) were elevated at early stages of embryogenesis, whereas at later stages amino acids and intermediates in the Krebs cycle were abundant. This agrees with zebrafish developmental biology, as organs such as the liver and pancreas develop at later stages. Thus, metabolomics of zebrafish embryos offers a unique opportunity to investigate large scale changes in metabolic processes during important developmental stages in vertebrate development. In terms of stability of the metabolic profile and viability of the embryos, it was concluded at 72 hpf was a suitable time point for the use of zebrafish as a model system in numerous scientific applications.

National Category
Developmental Biology
Identifiers
urn:nbn:se:uu:diva-387287 (URN)10.1371/journal.pone.0213661 (DOI)000467843000002 ()31086370 (PubMedID)
Funder
Swedish Research Council, 2011-6044Swedish Research Council, 2016-04376EU, FP7, Seventh Framework Programme, 238821
Available from: 2019-06-24 Created: 2019-06-24 Last updated: 2019-06-24Bibliographically approved
Torell, F., Bennet, K., Cereghini, S., Fabre, M., Rännar, S., Lundstedt-Enkel, K., . . . Lundstedt, T. (2018). Metabolic Profiling of Multiorgan Samples: Evaluation of MODY5/RCAD Mutant Mice. Journal of Proteome Research, 17(7), 2293-2306
Open this publication in new window or tab >>Metabolic Profiling of Multiorgan Samples: Evaluation of MODY5/RCAD Mutant Mice
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2018 (English)In: Journal of Proteome Research, ISSN 1535-3893, E-ISSN 1535-3907, Vol. 17, no 7, p. 2293-2306Article in journal (Refereed) Published
Abstract [en]

In the present study, we performed a metabolomics analysis to evaluate a MODY5/RCAD mouse mutant line as a potential model for HNF1B-associated diseases. Gas chromatography time-of-flight mass spectrometry (GC-TOF-MS) of gut, kidney, liver, muscle, pancreas, and plasma samples uncovered the tissue specific metabolite distribution. Orthogonal projections to latent structures discriminant analysis (OPLS-DA) was used to identify the differences between MODY5/RCAD and wild-type mice in each of the tissues. The differences included, for example, increased levels of amino acids in the kidneys and reduced levels of fatty acids in the muscles of the MODY5/RCAD mice. Interestingly, campesterol was found in higher concentrations in the MODY5/RCAD mice, with a four-fold and three-fold increase in kidneys and pancreas, respectively. As expected, the MODY5/RCAD mice displayed signs of impaired renal function in addition to disturbed liver lipid metabolism, with increased lipid and fatty acid accumulation in the liver. From a metabolomics perspective, the MODY5/RCAD model was proven to display a metabolic pattern similar to what would be suspected in HNF1B-associated diseases. These findings were in line with the presumed outcome of the mutation based on the different anatomy and function of the tissues as well as the effect of the mutation on development.

Keywords
HNF1B-associated diseases, metabolomics, OPLS-DA, multiorgan samples, MODY5, RCAD, mouse model
National Category
Endocrinology and Diabetes
Identifiers
urn:nbn:se:uu:diva-361549 (URN)10.1021/acs.jproteome.7b00821 (DOI)000438469900004 ()29873499 (PubMedID)
Funder
Swedish Research Council, 2011-6044Swedish Research Council, 2016-04376EU, FP7, Seventh Framework Programme
Available from: 2018-10-08 Created: 2018-10-08 Last updated: 2018-10-08Bibliographically approved
Morrell, J. M., Nongbua, T., Valeanu, S., Verde, I. L., Lundstedt-Enkel, K., Edman, A. & Johannisson, A. (2017). Sperm quality variables as indicators of bull fertility may be breed dependent. Animal Reproduction Science, 185, 42-52
Open this publication in new window or tab >>Sperm quality variables as indicators of bull fertility may be breed dependent
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2017 (English)In: Animal Reproduction Science, ISSN 0378-4320, E-ISSN 1873-2232, Vol. 185, p. 42-52Article in journal (Refereed) Published
Abstract [en]

A means of discriminating among bulls of high fertility based on sperm quality is needed by breeding centers. The objective of the study was to examine parameters of sperm quality in bulls of known fertility to identify useful indicators of fertility. Frozen semen was available from bulls of known fertility (Viking Genetics, Skara, Sweden): Swedish Red (n = 31), Holstein (n = 25) and Others (one each of Charolais, Limousin, Blonde, SKB). After thawing, the sperm samples were analyzed for motility (computer assisted sperm analysis), plasma membrane integrity, chromatin integrity, acrosome status, mitochondrial activity and reactive oxygen species. A fertility index score based on the adjusted 56-day non-return rate for > 1000 inseminations was available for each bull. Multivariate data analysis (Partial Least Squares Regression and Orthogonal Partial Least Squares Regression) was performed to identify variables related to fertility; Pearson univariate correlations were made on the parameters of interest. Breed of bull affected the relationship of sperm quality variables and fertility index score, as follows: Swedish Red: %DNA Fragmentation Index, r = -0.56, P < 0.01; intact plasma membrane, r = 0.40, P < 0.05; membrane damaged, not acrosome reacted, r = 0.6, P < 0.01; Linearity, r = 0.37, P < 0.05; there was a trend towards significance for Wobble, r = 0.34, P = 0.08. Holstein: Linearity was significant r = 0.46, P < 0.05; there was a trend towards significance for Wobble, r = 0.45, P = 0.08. In conclusion, breed has a greater effect on sperm quality than previously realized; different parameters of sperm quality are needed to indicate potential fertility in different breeds.

Place, publisher, year, edition, pages
ELSEVIER SCIENCE BV, 2017
Keywords
Sperm chromatin integrity, Plasma membrane integrity, Kinematics, Holstein, Swedish red
National Category
Agricultural and Veterinary sciences
Identifiers
urn:nbn:se:uu:diva-337117 (URN)10.1016/j.anireprosci.2017.08.001 (DOI)000412613700005 ()28811063 (PubMedID)
Available from: 2017-12-21 Created: 2017-12-21 Last updated: 2017-12-21Bibliographically approved
Torell, F., Bennett, K., Raennar, S., Lundstedt-Enkel, K., Lundstedt, T. & Trygg, J. (2017). The effects of thawing on the plasma metabolome: evaluating differences between thawed plasma and multi-organ samples. Metabolomics, 13(6), Article ID 66.
Open this publication in new window or tab >>The effects of thawing on the plasma metabolome: evaluating differences between thawed plasma and multi-organ samples
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2017 (English)In: Metabolomics, ISSN 1573-3882, E-ISSN 1573-3890, Vol. 13, no 6, article id 66Article in journal (Refereed) Published
Abstract [en]

Introduction Post-collection handling, storage and transportation can affect the quality of blood samples. Pre-analytical biases can easily be introduced and can jeopardize accurate profiling of the plasma metabolome. Consequently, a mouse study must be carefully planned in order to avoid any kind of bias that can be introduced, in order not to compromise the outcome of the study. The storage and shipment of the samples should be made in such a way that the freeze-thaw cycles are kept to a minimum. In order to keep the latent effects on the stability of the blood metabolome to a minimum it is essential to study the effect that the post-collection and pre-analytical error have on the metabolome.

Objectives The aim of this study was to investigate the effects of thawing on the metabolic profiles of different sample types.

Methods In the present study, a metabolomics approach was utilized to obtain a thawing profile of plasma samples obtained on three different days of experiment. The plasma samples were collected from the tail on day 1 and 3, while retro-orbital sampling was used on day 5. The samples were analysed using gas chromatography time-of-flight mass spectrometry (GC TOF-MS).

Results The thawed plasma samples were found to be characterized by higher levels of amino acids, fatty acids, glycerol metabolites and purine and pyrimidine metabolites as a result of protein degradation, cell degradation and increased phospholipase activity. The consensus profile was thereafter compared to the previously published study comparing thawing profiles of tissue samples from gut, kidney, liver, muscle and pancreas.

Conclusions The comparison between thawed organ samples and thawed plasma samples indicate that the organ samples are more sensitive to thawing, however thawing still affected all investigated sample types.

Keywords
Mouse, Metabolomics, Plasma, Multi-organ, Freeze-thaw cycle, OPLS-DA
National Category
Biochemistry and Molecular Biology
Identifiers
urn:nbn:se:uu:diva-323768 (URN)10.1007/s11306-017-1196-9 (DOI)000401711400001 ()28473743 (PubMedID)
Funder
Swedish Research Council, 2011-6044EU, FP7, Seventh Framework Programme
Available from: 2017-06-09 Created: 2017-06-09 Last updated: 2017-06-09Bibliographically approved
Morrell, J. M., Nongbua, T., Valeanu, S., Lundstedt-Enkel, K., Edman, A. & Johannisson, A. (2016). Bull breed affects which parameters of sperm quality are indicative of fertility. Paper presented at 10th Biennial Conference of the Association-for-Applied-Animal-Androl, JUN 24-26, 2016, Tours, FRANCE. Animal Reproduction Science, 169, 112-113
Open this publication in new window or tab >>Bull breed affects which parameters of sperm quality are indicative of fertility
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2016 (English)In: Animal Reproduction Science, ISSN 0378-4320, E-ISSN 1873-2232, Vol. 169, p. 112-113Article in journal, Meeting abstract (Other academic) Published
National Category
Medical Bioscience
Identifiers
urn:nbn:se:uu:diva-299767 (URN)10.1016/j.anireprosci.2016.03.046 (DOI)000377232600046 ()
Conference
10th Biennial Conference of the Association-for-Applied-Animal-Androl, JUN 24-26, 2016, Tours, FRANCE
Available from: 2016-07-27 Created: 2016-07-27 Last updated: 2017-11-28Bibliographically approved
Torell, F., Bennett, K., Cereghini, S., Rannar, S., Lundstedt-Enkel, K., Moritz, T., . . . Lundstedt, T. (2016). Tissue sample stability: thawing effect on multi-organ samples. Metabolomics, 12(2), Article ID 19.
Open this publication in new window or tab >>Tissue sample stability: thawing effect on multi-organ samples
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2016 (English)In: Metabolomics, ISSN 1573-3882, E-ISSN 1573-3890, Vol. 12, no 2, article id 19Article in journal (Refereed) Published
Abstract [en]

Correct handling of samples is essential in metabolomic studies. Improper handling and prolonged storage of samples has unwanted effects on the metabolite levels. The aim of this study was to identify the effects that thawing has on different organ samples. Organ samples from gut, kidney, liver, muscle and pancreas were analyzed for a number of endogenous metabolites in an untargeted metabolomics approach, using gas chromatography time of flight mass spectrometry at the Swedish Metabolomics Centre, Umeao University, Sweden. Multivariate data analysis was performed by means of principal component analysis and orthogonal projection to latent structures discriminant analysis. The results showed that the metabolic changes caused by thawing were almost identical for all organs. As expected, there was a marked increase in overall metabolite levels after thawing, caused by increased protein and cell degradation. Cholesterol was one of the eight metabolites found to be decreased in the thawed samples in all organ groups. The results also indicated that the muscles are less susceptible to oxidation compared to the rest of the organ samples.

Keywords
Thawing effect, Metabolomics, OPLS, Multivariate analysis, Multi-organ
National Category
Endocrinology and Diabetes
Identifiers
urn:nbn:se:uu:diva-280892 (URN)10.1007/s11306-015-0933-1 (DOI)000369343900010 ()
Funder
Swedish Research Council, 2011-6044
Available from: 2016-03-16 Created: 2016-03-16 Last updated: 2017-11-30Bibliographically approved
Berg, C., Lundstedt-Enkel, K., Olovsson, M. & Persson, S. (Eds.). (2013). Female Reproduction and Endocrine Disrupting Chemicals (FEMREP 2013). Paper presented at Female Reproduction and Endocrine Disrupting Chemicals (FEMREP 2013), Uppsala, 5-6 November, 2013.. Uppsala: Sveriges Lantbruksuniversitet
Open this publication in new window or tab >>Female Reproduction and Endocrine Disrupting Chemicals (FEMREP 2013)
2013 (English)Conference proceedings (editor) (Other academic)
Place, publisher, year, edition, pages
Uppsala: Sveriges Lantbruksuniversitet, 2013. p. 34
Series
CRU Report, ISSN 1404-5915 ; 28
National Category
Natural Sciences Medical and Health Sciences
Research subject
Biology with specialization in Environmental Toxicology; Toxicology; Family Medicine
Identifiers
urn:nbn:se:uu:diva-214184 (URN)978-91-576-9057-9 (ISBN)
Conference
Female Reproduction and Endocrine Disrupting Chemicals (FEMREP 2013), Uppsala, 5-6 November, 2013.
Available from: 2014-01-08 Created: 2014-01-08 Last updated: 2014-06-12Bibliographically approved
Dahlbom, S. J., Backström, T., Lundstedt-Enkel, K. & Winberg, S. (2012). Aggression and monoamines: Effects of sex and social rank in zebrafish (Danio rerio). Behavioural Brain Research, 228(2), 333-338
Open this publication in new window or tab >>Aggression and monoamines: Effects of sex and social rank in zebrafish (Danio rerio)
2012 (English)In: Behavioural Brain Research, ISSN 0166-4328, E-ISSN 1872-7549, Vol. 228, no 2, p. 333-338Article in journal (Refereed) Published
Abstract [en]

Social defeat is a common model for studies on depression. However, such models are most often used to study aggression in males and sex differences in depression may therefore be overseen. This study investigated the potential of the zebrafish (Danio rerio) as a model for male and female aggression. In addition, effects on the brain serotonergic and dopaminergic neurotransmitter systems after agonistic interaction are well studied in many species, but not in zebrafish. We wanted to explore whether the zebrafish follows the same patterns as many other species. Therefore, the effects of agonistic interaction on brain monoaminergic activity were studied in adult male and female wild-type zebrafish. The fish interacted in pairs with one of the same sex for five days during which agonistic behaviour was quantified daily. Clear dominant/subordinate relationships developed in all pairs, both in males and females. The frequency of aggressive acts increased over time but did not differ between male and female pairs. Further, we found that dyadic agonistic interaction resulted in elevated brain serotonergic activity in subordinate zebrafish, as indicated by elevated hindbrain 5-hydroxyindoleacetic acid to serotonin ratios (5-hydroxyindolacetic acid (5-HIAA)/5-hydroxytryptamine (5-HT) ratios). We also observed a sex difference in forebrain dopamine levels and forebrain 5-HIAA/5-HT ratios, with females displaying higher concentrations of dopamine but lower 5-HIAA/5-HT ratios than males. These results suggest that zebrafish is a suitable model for studies on female aggression and sex differences in brain monoaminergic neurotransmission.

Keywords
Dominance, Aggression, Zebrafish, Monoamine, Sex difference
National Category
Neurosciences
Identifiers
urn:nbn:se:uu:diva-168935 (URN)10.1016/j.bbr.2011.12.011 (DOI)000301318900012 ()
Available from: 2012-02-20 Created: 2012-02-20 Last updated: 2018-01-12Bibliographically approved
Dahlbom, J., Lagman, D., Lundstedt-Enkel, K., Sundström, F. & Winberg, S. (2011). Boldness predicts social status in zebrafish (Danio rerio). PLoS ONE, 6(8), Article ID e23565.
Open this publication in new window or tab >>Boldness predicts social status in zebrafish (Danio rerio)
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2011 (English)In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 6, no 8, article id e23565Article in journal (Refereed) Published
Abstract [en]

This study explored if boldness could be used to predict social status. First, boldness was assessed by monitoring individual zebrafish behaviour in (1) an unfamiliar barren environment with no shelter (open field), (2) the same environment when a roof was introduced as a shelter, and (3) when the roof was removed and an unfamiliar object (Lego® brick) was introduced. Next, after a resting period of minimum one week, social status of the fish was determined in a dyadic contest and dominant/subordinate individuals were determined as the winner/loser of two consecutive contests. Multivariate data analyses showed that males were bolder than females and that the behaviours expressed by the fish during the boldness tests could be used to predict which fish would later become dominant and subordinate in the ensuing dyadic contest. We conclude that bold behaviour is positively correlated to dominance in zebrafish and that boldness is not solely a consequence of social dominance.

National Category
Natural Sciences
Identifiers
urn:nbn:se:uu:diva-157531 (URN)10.1371/journal.pone.0023565 (DOI)000294121300060 ()
Available from: 2011-08-22 Created: 2011-08-22 Last updated: 2017-12-08Bibliographically approved
Berg, C., Lundstedt-Enkel, K., Malmsten, J. & Persson, S. (Eds.). (2011). Reproductive Disorders in Baltic Vertebrate Wildlife (BALTREP 2011): What is the status of, and the threats to reproductive health in Baltic region wildlife?. Paper presented at Reproductive Disorders in Baltic Vertebrate Wildlife (BALTREP 2011). What is the status of, and the threats to reproductive health in Baltic region wildlife?, Uppsala, December 7-8, 2011. Uppsala: SLU Service/Repro
Open this publication in new window or tab >>Reproductive Disorders in Baltic Vertebrate Wildlife (BALTREP 2011): What is the status of, and the threats to reproductive health in Baltic region wildlife?
2011 (English)Conference proceedings (editor) (Other academic)
Place, publisher, year, edition, pages
Uppsala: SLU Service/Repro, 2011. p. 68
Series
CRU report, ISSN 1404-5915 ; 26
National Category
Other Biological Topics
Research subject
Biology with specialization in Environmental Toxicology
Identifiers
urn:nbn:se:uu:diva-188636 (URN)978-91-576-9057-9 (ISBN)
Conference
Reproductive Disorders in Baltic Vertebrate Wildlife (BALTREP 2011). What is the status of, and the threats to reproductive health in Baltic region wildlife?, Uppsala, December 7-8, 2011
Available from: 2012-12-18 Created: 2012-12-18 Last updated: 2015-08-06Bibliographically approved
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