47 results on '"Bendt, Anne K"'
Search Results
2. Plasma lipidomic profiling reveals metabolic adaptations to pregnancy and signatures of cardiometabolic risk: a preconception and longitudinal cohort study
- Author
-
Chen, Li, Mir, Sartaj Ahmad, Bendt, Anne K., Chua, Esther W. L., Narasimhan, Kothandaraman, Tan, Karen Mei-Ling, Loy, See Ling, Tan, Kok Hian, Shek, Lynette P., Chan, Jerry, Yap, Fabian, Meaney, Michael J., Chan, Shiao-Yng, Chong, Yap Seng, Gluckman, Peter D., Eriksson, Johan G., Karnani, Neerja, and Wenk, Markus R.
- Published
- 2023
- Full Text
- View/download PDF
3. Lessons from the Singapore cohorts showcase symposium—open call for collaborations
- Author
-
Bendt, Anne K., Mir, Sartaj Ahmad, Maier, Andrea B., Goh, Jorming, Low, Ivan Cherh Chiet, Lee, Jason K. W., Koh, Angela S., Wenk, Markus R., and Adamski, Jerzy
- Published
- 2023
- Full Text
- View/download PDF
4. Understanding the systemic burden of disease in hidradenitis suppurativa from plasma lipidomic analysis
- Author
-
Choi, Ellie, Mir, Sartaj Ahmad, Ji, Shanshan, Ooi, Xue Ting, Chua, Esther W.L., Yi Wei, Yeo, Wenk, Markus R., Bendt, Anne K., and Chandran, Nisha Suyien
- Published
- 2022
- Full Text
- View/download PDF
5. Population-based plasma lipidomics reveals developmental changes in metabolism and signatures of obesity risk: a mother-offspring cohort study
- Author
-
Mir, Sartaj Ahmad, Chen, Li, Burugupalli, Satvika, Burla, Bo, Ji, Shanshan, Smith, Adam Alexander T., Narasimhan, Kothandaraman, Ramasamy, Adaikalavan, Tan, Karen Mei-Ling, Huynh, Kevin, Giles, Corey, Mei, Ding, Wong, Gerard, Yap, Fabian, Tan, Kok Hian, Collier, Fiona, Saffery, Richard, Vuillermin, Peter, Bendt, Anne K., Burgner, David, Ponsonby, Anne-Louise, Lee, Yung Seng, Chong, Yap Seng, Gluckman, Peter D., Eriksson, Johan G., Meikle, Peter J., Wenk, Markus R., and Karnani, Neerja
- Published
- 2022
- Full Text
- View/download PDF
6. Myo-inositol moderates maternal BMI and glycemia related variations in in-vitro placental 13C-DHA-metabolism, altering their relationships with birthweight
- Author
-
Watkins, Oliver C., Selvam, Preben, Pillai, Reshma Appukuttan, Cracknell-Hazra, Victoria K. B., Yong, Hannah E. J., Sharma, Neha, Cazenave-Gassiot, Amaury, Bendt, Anne K., Godfrey, Keith M., Lewis, Rohan M., Wenk, Markus R., and Chan, Shiao-Yng
- Published
- 2022
- Full Text
- View/download PDF
7. A global perspective on the status of clinical metabolomics in laboratory medicine – a survey by the IFCC metabolomics working group.
- Author
-
Fux, Elie, Lenski, Marie, Bendt, Anne K., Otvos, James D., Ivanisevic, Julijana, De Bruyne, Sander, Cavalier, Etienne, and Friedecký, David
- Subjects
TECHNOLOGICAL innovations ,LIPIDOMICS ,CLINICAL toxicology ,COMPLEX matrices ,METABOLOMICS - Abstract
Metabolomics aims for comprehensive characterization and measurement of small molecule metabolites (<1700 Da) in complex biological matrices. This study sought to assess the current understanding and usage of metabolomics in laboratory medicine globally and evaluate the perception of its promise and future implementation. A survey was conducted by the IFCC metabolomics working group that queried 400 professionals from 79 countries. Participants provided insights into their experience levels, knowledge, and usage of metabolomics approaches, along with detailing the applications and methodologies employed. Findings revealed a varying level of experience among respondents, with varying degrees of familiarity and utilization of metabolomics techniques. Targeted approaches dominated the field, particularly liquid chromatography coupled to a triple quadrupole mass spectrometer, with untargeted methods also receiving significant usage. Applications spanned clinical research, epidemiological studies, clinical diagnostics, patient monitoring, and prognostics across various medical domains, including metabolic diseases, endocrinology, oncology, cardiometabolic risk, neurodegeneration and clinical toxicology. Despite optimism for the future of clinical metabolomics, challenges such as technical complexity, standardization issues, and financial constraints remain significant hurdles. The study underscores the promising yet intricate landscape of metabolomics in clinical practice, emphasizing the need for continued efforts to overcome barriers and realize its full potential in patient care and precision medicine. [ABSTRACT FROM AUTHOR]
- Published
- 2024
- Full Text
- View/download PDF
8. Placental 13C-DHA metabolism and relationship with maternal BMI, glycemia and birthweight
- Author
-
Watkins, Oliver C., Selvam, Preben, Appukuttan Pillai, Reshma, Cracknell-Hazra, Victoria K. B., Yong, Hannah E. J., Sharma, Neha, Cazenave-Gassiot, Amaury, Bendt, Anne K., Godfrey, Keith M., Lewis, Rohan M., Wenk, Markus R., and Chan, Shiao-Yng
- Published
- 2021
- Full Text
- View/download PDF
9. Umbilical Cord Plasma Lysophospholipids and Triacylglycerols Associated with Birthweight Percentiles.
- Author
-
Wong, Gerard, Narasimhan, Kothandaraman, Cheong, Wei Fun, Ng, Sharon, Aris, Izzuddin M., Loy, See Ling, Bendt, Anne K., Tan, Kok Hian, Yap, Fabian K. P., Shek, Lynette P., Chong, Yap Seng, Gluckman, Peter D., Godfrey, Keith M., Lee, Yung Seng, Wenk, Markus R., Karnani, Neerja, and Chan, Shiao-Yng
- Abstract
Dysregulated transplacental lipid transfer and fetal–placental lipid metabolism affect birthweight, as does maternal hyperglycemia. As the mechanisms are unclear, we aimed to identify the lipids in umbilical cord plasma that were most associated with birthweight. Seventy-five Chinese women with singleton pregnancies recruited into the GUSTO mother–offspring cohort were selected from across the glycemic range based on a mid-gestation 75 g oral glucose tolerance test, excluding pre-existing diabetes. Cord plasma samples collected at term delivery were analyzed using targeted liquid-chromatography tandem mass-spectrometry to determine the concentrations of 404 lipid species across 17 lipid classes. The birthweights were standardized for sex and gestational age by local references, and regression analyses were adjusted for the maternal age, BMI, parity, mode of delivery, insulin treatment, and fasting/2 h glucose, with a false discovery-corrected p < 0.05 considered significant. Ten lysophosphatidylcholines (LPCs) and two lysophosphatidylethanolamines were positively associated with the birthweight percentiles, while twenty-four triacylglycerols were negatively associated with the birthweight percentiles. The topmost associated lipid was LPC 20:2 [21.28 (95%CI 12.70, 29.87) percentile increase in the standardized birthweight with each SD-unit increase in log
10 -transformed concentration]. Within these same regression models, maternal glycemia did not significantly associate with the birthweight percentiles. Specific fetal circulating lysophospholipids and triacylglycerols associate with birthweight independently of maternal glycemia, but a causal relationship remains to be established. [ABSTRACT FROM AUTHOR]- Published
- 2024
- Full Text
- View/download PDF
10. Lipidomic profiling of plasma in a healthy Singaporean population to identify ethnic specific differences in lipid levels and associations with disease risk factors
- Author
-
Begum, Husna, Torta, Federico, Narayanaswamy, Pradeep, Mundra, Piyushkumar A., Ji, Shanshan, Bendt, Anne K., Saw, Woei-Yuh, Teo, Yik Ying, Soong, Richie, Little, Peter F., Meikle, Peter J., and Wenk, Markus R.
- Published
- 2017
- Full Text
- View/download PDF
11. Changes in the Canine Plasma Lipidome after Short- and Long-Term Excess Glucocorticoid Exposure
- Author
-
Sieber-Ruckstuhl, Nadja S., Burla, Bo, Spoerel, Susanne, Schmid, Florence, Venzin, Claudio, Cazenave-Gassiot, Amaury, Bendt, Anne K., Torta, Federico, Wenk, Markus R., and Boretti, Felicitas S.
- Published
- 2019
- Full Text
- View/download PDF
12. Myo‐inositol alters the effects of glucose, leptin and insulin on placental palmitic acid and oleic acid metabolism.
- Author
-
Watkins, Oliver C., Pillai, Reshma Appukuttan, Selvam, Preben, Yong, Hannah E.J., Cracknell‐Hazra, Victoria K.B., Sharma, Neha, Cazenave‐Gassiot, Amaury, Bendt, Anne K., Godfrey, Keith M., Lewis, Rohan M., Wenk, Markus R., and Chan, Shiao‐Yng
- Abstract
Well‐regulated placental palmitic acid (PA) and oleic acid (OA) metabolism is vital for optimal placental function and fetal development, but dysregulation occurs with gestational diabetes (GDM). We hypothesized that such dysregulation might arise from increased maternofetal glucose, leptin or insulin concentrations present in GDM, and that dysregulated PA and OA lipid metabolism could be moderated by myo‐inositol, a natural polyol and potential GDM intervention. Placental explants from 21 women were incubated with stable isotope‐labelled 13C‐PA or 13C‐OA for 48 h. Explants were treated with glucose (5, 10 mm) or leptin (13 nm) or insulin (150 nm) in combination with myo‐inositol (0.3, 30, 60 μm). Forty‐seven 13C‐PA lipids and 37 13C‐OA lipids were measured by liquid chromatography–mass spectrometry (LCMS). Compared with controls (5 mm glucose), glucose (10 mm) increased 19 13C‐OA lipids and nine 13C‐PA lipids, but decreased 13C‐OA phosphatidylethanolamine 38:5 and 13C‐PA phosphatidylethanolamine 36:4. The effects of leptin and insulin were less prominent than glucose, with leptin increasing 13C‐OA acylcarnitine 18:1, and insulin increasing four 13C‐PA triacylglycerides. Most glucose, leptin and insulin‐induced alterations in lipids were attenuated by co‐incubation with myo‐inositol (30 or 60 μm), with attenuation also occurring in all subgroups stratified by GDM status and fetal sex. However, glucose‐induced increases in acylcarnitine were not attenuated by myo‐inositol and were even exaggerated in some instances. Myo‐inositol therefore appears to generally act as a moderator, suppressing the perturbation of lipid metabolic processes by glucose, leptin and insulin in placenta in vitro. Whether myo‐inositol protects the fetus and pregnancy from unfavourable outcomes requires further research. Key points: Incubation of placental explants with additional glucose, or to a lesser extent insulin or leptin, alters the placental production of 13C‐lipids from 13C‐palmitic acid (PA) and 13C‐oleic acid (OA) in vitro compared with untreated controls from the same placenta.Co‐incubation with myo‐inositol attenuated most alterations induced by glucose, insulin or leptin in 13C‐lipids, but did not affect alterations in 13C‐acylcarnitines.Alterations induced by glucose and leptin in 13C‐PA triacylglycerides and 13C‐PA phospholipids were influenced by fetal sex and gestational diabetes status, but were all still attenuated by myo‐inositol co‐incubation.Insulin differently affected 13C‐PA triacylglycerides and 13C‐PA phospholipids depending on fetal sex, with alterations also attenuated by myo‐inositol co‐incubation. [ABSTRACT FROM AUTHOR]
- Published
- 2023
- Full Text
- View/download PDF
13. From research cohorts to the patient – a role for "omics" in diagnostics and laboratory medicine?
- Author
-
Vogeser, Michael and Bendt, Anne K.
- Subjects
- *
PATTERN recognition systems , *CLINICAL pathology , *BIOMOLECULES , *ARTIFICIAL intelligence , *GLYCANS , *GENETIC translation , *NANOMEDICINE - Abstract
Human pathologies are complex and might benefit from a more holistic diagnostic approach than currently practiced. Omics is a concept in biological research that aims to comprehensively characterize and quantify large numbers of biological molecules in complex samples, e.g., proteins (proteomics), low molecular weight molecules (metabolomics), glycans (glycomics) or amphiphilic molecules (lipidomics). Over the past decades, respective unbiased discovery approaches have been intensively applied to investigate functional physiological and pathophysiological relationships in various research study cohorts. In the context of clinical diagnostics, omics approaches seem to have potential in two main areas: (i) biomarker discovery i.e. identification of individual marker analytes for subsequent translation into diagnostics (as classical target analyses with conventional laboratory techniques), and (ii) the readout of complex, higher-dimensional signatures of diagnostic samples, in particular by means of spectrometric techniques in combination with biomathematical approaches of pattern recognition and artificial intelligence for diagnostic classification. Resulting diagnostic methods could potentially represent a disruptive paradigm shift away from current one-dimensional (i.e., single analyte marker based) laboratory diagnostics. The underlying hypothesis of omics approaches for diagnostics is that complex, multigenic pathologies can be more accurately diagnosed via the readout of "omics-type signatures" than with the current one-dimensional single marker diagnostic procedures. While this is indeed promising, one must realize that the clinical translation of high-dimensional analytical procedures into routine diagnostics brings completely new challenges with respect to long-term reproducibility and analytical standardization, data management, and quality assurance. In this article, the conceivable opportunities and challenges of omics-based laboratory diagnostics are discussed. [ABSTRACT FROM AUTHOR]
- Published
- 2023
- Full Text
- View/download PDF
14. Clinical lipidomics – A community-driven roadmap to translate research into clinical applications
- Author
-
Vvedenskaya, Olga, Holčapek, Michal, Vogeser, Michael, Ekroos, Kim, Meikle, Peter J., and Bendt, Anne K.
- Published
- 2022
- Full Text
- View/download PDF
15. Myo-Inositol Moderates Glucose-Induced Effects on Human Placental 13 C-Arachidonic Acid Metabolism.
- Author
-
Watkins, Oliver C., Cracknell-Hazra, Victoria K. B., Pillai, Reshma Appukuttan, Selvam, Preben, Yong, Hannah E. J., Sharma, Neha, Patmanathan, Sathya Narayanan, Cazenave-Gassiot, Amaury, Bendt, Anne K., Godfrey, Keith M., Lewis, Rohan M., Wenk, Markus R., and Chan, Shiao-Yng
- Abstract
Maternal hyperglycemia is associated with disrupted transplacental arachidonic acid (AA) supply and eicosanoid synthesis, which contribute to adverse pregnancy outcomes. Since placental inositol is lowered with increasing glycemia, and since myo-inositol appears a promising intervention for gestational diabetes, we hypothesized that myo-inositol might rectify glucose-induced perturbations in placental AA metabolism. Term placental explants (n = 19) from women who underwent a mid-gestation oral glucose-tolerance-test were cultured with
13 C-AA for 48 h in media containing glucose (5, 10 or 17 mM) and myo-inositol (0.3 or 60 µM). Newly synthesized13 C-AA-lipids were quantified by liquid-chromatography-mass-spectrometry. Increasing maternal fasting glycemia was associated with decreased proportions of13 C-AA-phosphatidyl-ethanolamines (PE, PE-P), but increased proportions of13 C-AA-triacylglycerides (TGs) relative to total placental13 C-AA lipids. This suggests altered placental AA compartmentalization towards storage and away from pools utilized for eicosanoid production and fetal AA supply. Compared to controls (5 mM glucose), 10 mM glucose treatment decreased the amount of four13 C-AA-phospholipids and eleven13 C-AA-TGs, whilst 17 mM glucose increased13 C-AA-PC-40:8 and13 C-AA-LPC. Glucose-induced alterations in all13 C-AA lipids (except PE-P-38:4) were attenuated by concurrent 60 µM myo-inositol treatment. Myo-inositol therefore rectifies some glucose-induced effects, but further studies are required to determine if maternal myo-inositol supplementation could reduce AA-associated pregnancy complications. [ABSTRACT FROM AUTHOR]- Published
- 2022
- Full Text
- View/download PDF
16. Characterisation of secreted lipids by human term placental trophoblast in vitro.
- Author
-
Juen Yong, Hannah Ee, Wee, Hai Ning, Watkins, Oliver C., Lee, Swee Leng, Lin Mah, Tania Ken, Cazenave-Gassiot, Amaury, Bendt, Anne K., Wenk, Markus R., and Chan, Shiao-Yng
- Published
- 2024
- Full Text
- View/download PDF
17. Association of preconception maternal metabolic factors with placental lipid profile, and its impact on birth weight in the NiPPeR study.
- Author
-
Wee, Hai Ning, Cracknell-Hazra, Victoria K.B., Juen Yong, Hannah Ee, Watkins, Oliver C., Cazenave-Gassiot, Amaury, Bendt, Anne K., Wenk, Markus R., Barton, Sheila J., Lewis, Rohan M., Cutfield, Wayne S., Godfrey, Keith M., and Chan, Shiao-Yng
- Published
- 2024
- Full Text
- View/download PDF
18. MS-based lipidomics of human blood plasma: a community-initiated position paper to develop accepted guidelines1
- Author
-
Burla, Bo, Arita, Makoto, Arita, Masanori, Bendt, Anne K., Cazenave-Gassiot, Amaury, Dennis, Edward A., Ekroos, Kim, Han, Xianlin, Ikeda, Kazutaka, Liebisch, Gerhard, Lin, Michelle K., Loh, Tze Ping, Meikle, Peter J., Orešič, Matej, Quehenberger, Oswald, Shevchenko, Andrej, Torta, Federico, Wakelam, Michael J. O., Wheelock, Craig E., and Wenk, Markus R.
- Subjects
Male ,Blood Specimen Collection ,clinical trials ,data sharing ,National Institute of Standards and Technology Standard Reference Material 1950 ,Guidelines as Topic ,QD415-436 ,Reference Standards ,Biochemistry ,diagnostic tools ,absolute concentrations ,lipids ,clinical research ,Humans ,Female ,quality control ,Patient-Oriented and Epidemiological Research ,Blood Chemical Analysis ,Demography ,mass spectrometry - Abstract
Human blood is a self-regenerating lipid-rich biological fluid that is routinely collected in hospital settings. The inventory of lipid molecules found in blood plasma (plasma lipidome) offers insights into individual metabolism and physiology in health and disease. Disturbances in the plasma lipidome also occur in conditions that are not directly linked to lipid metabolism; therefore, plasma lipidomics based on MS is an emerging tool in an array of clinical diagnostics and disease management. However, challenges exist in the translation of such lipidomic data to clinical applications. These relate to the reproducibility, accuracy, and precision of lipid quantitation, study design, sample handling, and data sharing. This position paper emerged from a workshop that initiated a community-led process to elaborate and define a set of generally accepted guidelines for quantitative MS-based lipidomics of blood plasma or serum, with harmonization of data acquired on different instrumentation platforms across independent laboratories as an ultimate goal. We hope that other fields may benefit from and follow such a precedent.
- Published
- 2018
19. Myo-inositol moderates maternal BMI and glycemia related variations in in-vitro placental 13C-DHA-metabolism, altering their relationships with birthweight.
- Author
-
Watkins, Oliver C., Selvam, Preben, Pillai, Reshma Appukuttan, Cracknell-Hazra, Victoria K. B., Yong, Hannah E. J., Sharma, Neha, Cazenave-Gassiot, Amaury, Bendt, Anne K., Godfrey, Keith M., Lewis, Rohan M., Wenk, Markus R., and Chan, Shiao-Yng
- Subjects
HYPERGLYCEMIA ,PLACENTA ,BIRTH weight ,PROCESS capability ,GESTATIONAL diabetes ,FETAL development - Abstract
Transplacental docosahexaenoic-acid (DHA) supply for fetal development is regulated by placental DHA-lipid metabolism. Both maternal diabetes and obesity are linked to possible decreased fetal circulating DHA and increased placental DHA-lipids. Since myo-inositol is a promising intervention for gestational diabetes (GDM), we aimed to determine whether myo-inositol could rectify perturbations in placental DHA metabolism associated with maternal increasing glycemia and obesity and examine links with birthweight. Term placental villous explants from 17 women representing a range of BMIs and mid-gestational glycemia, were incubated with
13 C-labeled-DHA for 48 h, in 0.3 µmol/L (control) or 60 µmol/L myo-inositol. Individual newly synthesized13 C-DHA-labeled lipid species were quantified by liquid-chromatography-mass-spectrometry. Compared with controls, incubation with myo-inositol decreased most13 C-DHA-lipids in placental explants from women with higher BMI or higher glycemia, but increased13 C-DHA-lipids with normal BMI or lower glycemia. Myo-inositol also increased13 C-DHA-labeled lipids in cases of lower birthweight centile, but induced decreases at higher centiles. Myo-inositol therefore lowered DHA-lipids in placenta with high basal placental DHA-lipid production (higher BMI and glycemia) but increased DHA-lipids where basal processing capacity is low. Myo-inositol thus moderates placental DHA metabolism towards a physiological mean which may in turn moderate birthweight. [ABSTRACT FROM AUTHOR]- Published
- 2022
- Full Text
- View/download PDF
20. Lipid bilayer composition as a determinant of cancer cell sensitivity to tumoricidal protein‐lipid complexes.
- Author
-
Ho, James C. S., Mir, Sartaj Ahmad, Cavalera, Michele, Esmaeili, Parisa, Tran, Tuan Hiep, Yann, Zandra Chew, Tran, Thi Hien, Chaudhuri, Arunima, Bendt, Anne K., Wenk, Markus R., and Svanborg, Catharina
- Subjects
MEMBRANE lipids ,CELL membranes ,QUARTZ crystal microbalances ,CANCER cells ,BILAYER lipid membranes - Abstract
Complexes formed by the alpha1 N‐terminal peptide of alpha‐lactalbumin and oleic acid (alpha1‐oleate) interact with lipid bilayers. Plasma membrane perturbations trigger tumor cell death but normal differentiated cells are more resistant, and their plasma membranes are less strongly affected. This study examined membrane lipid composition as a determinant of tumor cell reactivity. Bladder cancer tissue showed a higher abundance of unsaturated lipids enriched in phosphatidylcholine, PC (36:4) and PC (38:4), and sphingomyelin, SM (36:1) than healthy bladder tissue, where saturated lipids predominated and the lipid extracts from bladder cancer tissue inhibited the tumoricidal effect of the complex more effectively than healthy tissue extracts. Furthermore, unsaturated PC in solution inhibited tumor cell death, and the complex interacted with giant unilamellar vesicles formed by PC, confirming the affinity of alpha1‐oleate for fluid membranes enriched in PC. Quartz Crystal Microbalance with dissipation monitoring (QCM‐D) detected a preference of the complex for the liquid‐disordered phase, suggesting that the insertion into PC‐based membranes and the resulting membrane perturbations are influenced by membrane lipid saturation. The results suggest that the membrane lipid composition is functionally important and that specific unsaturated membrane lipids may serve as "recognition motifs" for broad‐spectrum tumoricidal molecules such as alpha1‐oleate. [ABSTRACT FROM AUTHOR]
- Published
- 2022
- Full Text
- View/download PDF
21. Sex-Dependent Regulation of Placental Oleic Acid and Palmitic Acid Metabolism by Maternal Glycemia and Associations with Birthweight.
- Author
-
Watkins, Oliver C., Yong, Hannah E. J., Mah, Tania Ken Lin, Cracknell-Hazra, Victoria K. B., Pillai, Reshma Appukuttan, Selvam, Preben, Sharma, Neha, Cazenave-Gassiot, Amaury, Bendt, Anne K., Godfrey, Keith M., Lewis, Rohan M., Wenk, Markus R., and Chan, Shiao-Yng
- Subjects
PALMITIC acid ,OLEIC acid ,BIRTH weight ,PLACENTA ,METABOLISM ,LIPID metabolism ,ABRUPTIO placentae - Abstract
Pregnancy complications such as maternal hyperglycemia increase perinatal mortality and morbidity, but risks are higher in males than in females. We hypothesized that fetal sex-dependent differences in placental palmitic-acid (PA) and oleic-acid (OA) metabolism influence such risks. Placental explants (n = 22) were incubated with isotope-labeled fatty acids (
13 C-PA or13 C-OA) for 24 or 48 h and the production of forty-seven13 C-PA lipids and thirty-seven13 C-OA lipids quantified by LCMS. Linear regression was used to investigate associations between maternal glycemia, BMI and fetal sex with13 C lipids, and between13 C lipids and birthweight centile. Placental explants from females showed greater incorporation of13 C-OA and13 C-PA into almost all lipids compared to males. Fetal sex also influenced relationships with maternal glycemia, with many13 C-OA and13 C-PA acylcarnitines,13 C-PA-diacylglycerols and13 C-PA phospholipids positively associated with glycemia in females but not in males. In contrast, several13 C-OA triacylglycerols and13 C-OA phospholipids were negatively associated with glycemia in males but not in females. Birthweight centile in females was positively associated with six13 C-PA and three13 C-OA lipids (mainly acylcarnitines) and was negatively associated with eight13 C-OA lipids, while males showed few associations. Fetal sex thus influences placental lipid metabolism and could be a key modulator of the impact of maternal metabolic health on perinatal outcomes, potentially contributing toward sex-specific adaptions in which females prioritize survival. [ABSTRACT FROM AUTHOR]- Published
- 2022
- Full Text
- View/download PDF
22. Evaluation of Normalization Approaches for Quantitative Analysis of Bile Acids in Human Feces.
- Author
-
Schött, Hans-Frieder, Chua, Esther W. L., Mir, Sartaj Ahmad, Burla, Bo, Bendt, Anne K., and Wenk, Markus R.
- Subjects
BILE acids ,ACID analysis ,DEOXYCHOLIC acid ,FECES ,PLANT fibers ,QUANTITATIVE research - Abstract
Quantitative analysis of bile acids in human feces can potentially help to better understand the influence of the gut microbiome and diet on human health. Feces is a highly heterogeneous sample matrix, mainly consisting of water and indigestible solid material (as plant fibers) that show high inter-individual variability. To compare bile acid concentrations among different individuals, a reliable normalization approach is needed. Here, we compared the impact of three normalization approaches, namely sample wet weight, dry weight, and protein concentration, on the absolute concentrations of fecal bile acids. Bile acid concentrations were determined in 70 feces samples from healthy humans. Our data show that bile acid concentrations normalized by the three different approaches are substantially different for each individual sample. Fecal bile acid concentrations normalized by wet weight show the narrowest distribution. Therefore, our analysis will provide the basis for the selection of a suitable normalization approach for the quantitative analysis of bile acids in feces. [ABSTRACT FROM AUTHOR]
- Published
- 2022
- Full Text
- View/download PDF
23. Triacylglycerol utilization is required for regrowth of in vitro hypoxic nonreplicating Mycobacterium bovis Bacillus Calmette-Guerin
- Author
-
Low, Kai Leng, Rao, P.S. Srinivasa, Shui, Guanghou, Bendt, Anne K., Pethe, Kevin, Dick, Thomas, and Wenk, Markus R.
- Subjects
Triglycerides -- Physiological aspects ,Mycobacterium bovis -- Growth ,Company growth ,Biological sciences - Abstract
Mycobacteria store triacylglycerols (TGs) under various stress conditions, such as hypoxia, exposure to nitric oxide, and acidic environments. These stress conditions are known to induce nonreplicating persistence in mycobacteria. The importance of TG accumulation and utilization during regrowth is not clearly understood. Here we specifically determined the levels of accumulated TG and TG lipase activity in Mycobacterium bovis bacillus Calmette-Guerin (BCG) in various different physiological states (logarithmic growth, aerated stationary phase, hypoxia-induced dormancy, and regrowth from dormancy). We found extensive accumulation and degradation of TGs in the bacilli during entry into and exit from hypoxia-induced dormancy, respectively. These processes are accompanied by dynamic appearance and disappearance of intracellular TG lipid particles. The reduction in TG levels coincides with an increase in cellular TG lipase activity in the regrowing bacilli. Tetrahydrolipstatin, an inhibitor of TG lipases, reduces total lipase activity, prevents breakdown of TGs, and blocks the growth of mycobacteria upon resuscitation with air. Our results demonstrate that utilization of TGs is essential for the regrowth of mycobacteria during their exit from the hypoxic nonreplicating state.
- Published
- 2009
24. Myo-inositol alters C-labelled fatty acid metabolism in human placental explants
- Author
-
Watkins, Oliver C., Islam, Mohammed Omedul, Selvam, Preben, Pillai, Reshma Appukuttan, Cazenave-Gassiot, Amaury, Bendt, Anne K., Karmani, Neerja, Godfrey, Keith, Lewis, Rohan, Wenk, Markus R., and Chan, Shiao-Yng
- Subjects
lipids (amino acids, peptides, and proteins) - Abstract
We postulate that myo-inositol, a proposed intervention for gestational-diabetes, affects transplacental lipid supply to the fetus. We investigated the effect of myo-inositol on fatty-acid processing in human placental-explants from uncomplicated pregnancies. Explants were incubated with 13C-labeled palmitic-acid, 13C-oleic-acid and 13C-docosahexaenoic-acid across a range of myo-inositol concentrations for 24 h and 48 h. The incorporation of labeled-fatty-acids into individual lipids was quantified by liquid-chromatography-mass-spectrometry. At 24 h, myo-inositol increased the amount of 13C-palmitic-acid and 13C-oleic-acid labeled lipids (median fold-change relative to control=1). Significant effects were seen with 30 µM myo-inositol (physiological) for 13C-palmitic-acid-lysophosphatidylcholines (1.26) and 13C-palmitic-acid-phosphatidylethanolamines (1.17). At 48 h, myo-inositol addition increased 13C-oleic-acid-lipids but decreased 13C-palmitic-acid and 13C-docosahexaenoic-acid lipids. Significant effects were seen with 30 µM myo-inositol for 13C-oleic-acid-phosphatidylcholines (1.25), 13C-oleic-acid-phosphatidylethanolamines (1.37) and 13C-oleic-acid-triacylglycerols (1.32) and with 100 µM myo-inositol for 13C-docosahexaenoic-acid-triacylglycerols (0.78). Lipids labeled with the same 13C-fatty-acid showed similar responses when tested at the same time-point, suggesting myo-inositol alters upstream processes such as fatty-acid uptake or activation. Myo-inositol supplementation may alter placental lipid physiology with unknown clinical consequences.
- Published
- 2019
25. Utilization of creatinine as an alternative nitrogen source in Corynebacterium glutamicum
- Author
-
Bendt, Anne K., Beckers, Gabriele, Silberbach, Maike, Wittmann, Anja, and Burkovski, Andreas
- Published
- 2004
- Full Text
- View/download PDF
26. Molecular identification of the urea uptake system and transcriptional analysis of urea transporter- and urease-encoding genes in Corynebacterium glutamicum
- Author
-
Beckers, Gabriele, Bendt, Anne K., Kramer, Reinhard, and Burkovski, Andreas
- Subjects
Corynebacteria -- Research ,Corynebacteria -- Genetic aspects ,Bacteriology -- Research ,Repressor proteins ,Biological sciences - Abstract
The molecular identification of the Corynebaeterium glutamicum urea uptake system is described. This ABC-type transporter is encoded by the urtABCDE operon, which is transcribed in response to nitrogen limitation. Expression of the urt genes is regulated by the global nitrogen regulator AmtR, and an amtR deletion strain showed constitutive expression of the urtABCDE genes. The AmtR repressor protein also controls transcription of the urease-encoding ureABCEFGD genes in C. glutamicum. The ure gene cluster forms an operon which is mainly transcribed in response to nitrogen starvation. To confirm the increased synthesis of urease subunits under nitrogen limitation, proteome analyses of cytoplasmic protein extracts from cells grown under nitrogen surplus and nitrogen limitation were carried out, and five of the seven urease subunits were identified.
- Published
- 2004
27. Mycolic acids as diagnostic markers for tuberculosis case detection in humans and drug efficacy in mice
- Author
-
Shui, Guanghou, Bendt, Anne K., Jappar, Ignasius A., Lim, Hui Ming, Laneelle, Marie, Hervé, Maxime, Via, Laura E., Chua, Gek Huey, Bratschi, Martin W., Rahim, Siti Zarina Zainul, Michelle, Ang Lay Teng, Hwang, Soo-Hee, Lee, Jong-Soek, Eum, Seok-Yong, Kwak, Hyun-Kyung, Daffé, Mamadou, Dartois, Véronique, Michel, Gerd, Barry, Clifton E., and Wenk, Markus R.
- Published
- 2012
- Full Text
- View/download PDF
28. Myo-inositol alters 13C-labeled fatty acid metabolism in human placental explants.
- Author
-
Watkins, Oliver C., Islam, Mohammed Omedul, Selvam, Preben, Pillai, Reshma Appukuttan, Cazenave-Gassiot, Amaury, Bendt, Anne K., Karnani, Neerja, Godfrey, Keith M., Lewis, Rohan M., Wenk, Markus R., and Shiao-Yng Chan
- Subjects
FATTY acids ,PALMITIC acid ,METABOLISM ,GESTATIONAL diabetes ,PATHOLOGICAL physiology - Abstract
We postulate that myo-inositol, a proposed intervention for gestational diabetes, affects transplacental lipid supply to the fetus. We investigate d the effect of myoinositol on fatty acid processing in human placental explants from uncomplicated pregnancies. Explants were incubated with 13C-labeled palmitic acid,
13 C-oleic acid and13 C-docosahexaenoic acid across a range of myo-inositol concentrations for 24 h and 48 h. The incorporation of labeled fatty acids into in dividual lipids was quantified by liquid chromatography mass spectrometry. At 24 h, myo-inositol increased the amount of13 C-palmitic acid and13 C-oleic-acid labeled lipids (median fold change relative to control = 1). Significant effects were seen with 30 µM myo-inositol (physiological) for13 C-palmitic acid-lysophosphatidylcholines (1.26) and13 C-palmitic acidphosphatidylethanolamines (1.17). At 48 h, myo-inositol addition increased13 C-oleic-acidlipids but decreased13 C-palmitic acid and13 C-docosahexaenoic-acid lipids. Significant effects were seen with 30 µM myo-inositol for13 C-oleic-acid-phosphatidylcholines (1.25),13 C-oleic-acid-phosphatidylethanolamines (1.37) and13 C-oleic-acid-triacylglycerols (1.32) and with 100 µM myo-inositol for13 C-docosahexaenoic-acid-triacylglycerols (0.78). Lipids labeled with the same13 C-fatty acid showed similar responses when tested at the same time point, suggesting myo-inositol alters upstream processes such as fatty acid uptake or activation. Myo-inositol supplementation may alter placental lipid physiology with unknown clinical consequences. [ABSTRACT FROM AUTHOR]- Published
- 2019
- Full Text
- View/download PDF
29. Metabolism of 13 C-Labeled Fatty Acids in Term Human Placental Explants by Liquid Chromatography–Mass Spectrometry.
- Author
-
Watkins, Oliver C, Islam, Mohammad Omedul, Selvam, Preben, Pillai, Reshma Appukuttan, Cazenave-Gassiot, Amaury, Bendt, Anne K, Karnani, Neerja, Godfrey, Keith M, Lewis, Rohan M, Wenk, Markus R, and Chan, Shiao-Yng
- Published
- 2019
- Full Text
- View/download PDF
30. Identification of mycolic acid forms using surface-enhanced Raman scattering as a fast detection method for tuberculosis.
- Author
-
Perumal, Jayakumar, Dinish, US, Bendt, Anne K, Kazakeviciute, Agne, Fu, Chit Yaw, Ong, Irvine Lian Hao, and Olivo, Malini
- Published
- 2018
- Full Text
- View/download PDF
31. Mesoporous polymeric microspheres with high affinity for phosphorylated biomolecules.
- Author
-
Shinde, Sudhirkumar, Selvalatchmanan, Jayashree, Incel, Anil, Akhoundian, Maedeh, Bendt, Anne K., and Torta, Federico
- Subjects
MESOPOROUS materials ,PHOSPHORYLATION ,CHEMICAL affinity - Abstract
Phosphate plays a central role in the environment and in biology. This has led to the demand for a specific phosphate receptor that can be used to sense, enrich or separate phosphate and phosphorylated molecules from complex mixtures. Here, we report an approach for the production of phospho-affinity porous beads with controllable size and pore structure leading to significantly improved chromatographic properties. The beads were prepared by polymerization of bis-imidazolium based host monomer and crosslinker inside the pores of macroporous silica beads that post-etching resulted in mesoporous polymer replicas. The silica precursor, silica–polymer composite and porous polymer replica were characterized by using SEM, IR spectroscopy, optical microscopy and thermogravimetric analysis. Bis-imidazolium functionalized materials were capable of binding and enriching the signaling lipid sphingosine-1-phosphate from plasma samples. Moreover, these engineered materials combined with artificial receptors can recognize phosphorylated amino acids/peptides and are applicable to selective recognition of a broad class of phosphorylated biomolecules. [ABSTRACT FROM AUTHOR]
- Published
- 2018
- Full Text
- View/download PDF
32. Lipidomics and genomics of Mycobacterium tuberculosis reveal lineage-specific trends in mycolic acid biosynthesis.
- Author
-
Portevin, Damien, Sukumar, Sudarkodi, Coscolla, Mireia, Shui, Guanghou, Li, Bowen, Guan, Xue Li, Bendt, Anne K., Young, Douglas, Gagneux, Sebastien, and Wenk, Markus R.
- Published
- 2014
- Full Text
- View/download PDF
33. Host/ Malassezia Interaction: A Quantitative, Non-Invasive Method Profiling Oxylipin Production Associates Human Skin Eicosanoids with Malassezia.
- Author
-
Ambaw, Yohannes Abere, Pagac, Martin P., Irudayaswamy, Antony S., Raida, Manfred, Bendt, Anne K., Torta, Federico T., Wenk, Markus R., and Dawson Jr., Thomas L.
- Subjects
EICOSANOIDS ,MALASSEZIA ,HOST plants ,OXYLIPINS - Abstract
Malassezia are common components of human skin, and as the dominant human skin eukaryotic microbe, they take part in complex microbe–host interactions. Other phylogenetically related fungi (including within Ustilagomycotina) communicate with their plant host through bioactive oxygenated polyunsaturated fatty acids, generally known as oxylipins, by regulating the plant immune system to increase their virulence. Oxylipins are similar in structure and function to human eicosanoids, which modulate the human immune system. This study reports the development of a highly sensitive mass-spectrometry-based method to capture and quantify bioactive oxygenated polyunsaturated fatty acids from the human skin surface and in vitro Malassezia cultures. It confirms that Malassezia are capable of synthesizing eicosanoid-like lipid mediators in vitro in a species dependent manner, many of which are found on human skin. This method enables sensitive identification and quantification of bioactive lipid mediators from human skin that may be derived from metabolic pathways shared between skin and its microbial residents. This enables better cross-disciplinary and detailed studies to dissect the interaction between Malassezia and human skin, and to identify potential intervention points to promote or abrogate inflammation and to improve human skin health. [ABSTRACT FROM AUTHOR]
- Published
- 2021
- Full Text
- View/download PDF
34. Proteome analysis of Corynebacterium glutamicum.
- Author
-
Hermann, Thomas, Pfefferle, Walter, Baumann, Christian, Busker, Eberhard, Schaffer, Steffen, Bott, Michael, Sahm, Hermann, Dusch, Nicole, Kalinowski, Jörn, Pühler, Alfred, Bendt, Anne K., Krämer, Reinhard, and Burkovski, Andreas
- Published
- 2001
- Full Text
- View/download PDF
35. Healthy Breastfeeding Infants Consume Different Quantities of Milk Fat Globule Membrane Lipids.
- Author
-
George, Alexandra D., Gay, Melvin C. L., Selvalatchmanan, Jayashree, Torta, Federico, Bendt, Anne K., Wenk, Markus R., Murray, Kevin, Wlodek, Mary E., and Geddes, Donna T.
- Abstract
The human milk fat globule membrane (MFGM) contains important lipids for growing infants. Anthropometric measurements, milk samples, and infant milk intake were collected in a cohort of eleven healthy mother–infant dyads during exclusive breastfeeding from birth to six months. One hundred and sixty-six MFGM lipids were analysed using liquid chromatography-mass spectrometry, and the infant intake was calculated. The concentrations and intake were compared and associations between infant intake and growth characteristics explored. The lipid concentrations and infant intake varied widely between mother–infant dyads and between months one and three. The infant intake for many species displayed positive correlations with infant growth, particularly phospholipid species. The high variation in lipid intake is likely an important factor in infant growth, with strong correlations identified between the intake of many MFGM lipids and infant head circumference and weight. This study highlights the need for intake measurements and inclusion in cohort studies to elucidate the role of the human milk lipidome in infant growth and development. [ABSTRACT FROM AUTHOR]
- Published
- 2021
- Full Text
- View/download PDF
36. Lipidomic Analysis of Archival Pathology Specimens Identifies Altered Lipid Signatures in Ovarian Clear Cell Carcinoma.
- Author
-
Mir, Sartaj Ahmad, Wong, Soon Boon Justin, Narasimhan, Kothandaraman, Esther, Chua W. L., Ji, Shanshan, Burla, Bo, Wenk, Markus R., Tan, David S. P., and Bendt, Anne K.
- Subjects
FATTY acid analysis ,MONOUNSATURATED fatty acids ,UNSATURATED fatty acids ,LIPIDS ,LIQUID chromatography-mass spectrometry ,PARAFFIN wax - Abstract
Cancer metabolism is associated with the enhanced lipogenesis required for rapid growth and proliferation. However, the magnitude of dysregulation of diverse lipid species still requires significant characterization, particularly in ovarian clear cell carcinoma (OCCC). Here, we have implemented a robust sample preparation workflow together with targeted LC-MS/MS to identify the lipidomic changes in formalin-fixed paraffin-embedded specimens from OCCC compared to tumor-free ovarian tissue. We quantitated 340 lipid species, representing 28 lipid classes. We observed differential regulation of diverse lipid species belonging to several glycerophospholipid classes and trihexosylceramide. A number of unsaturated lipid species were increased in OCCC, whereas saturated lipid species showed a decrease in OCCC compared to the controls. We also carried out total fatty acid analysis and observed an increase in the levels of several unsaturated fatty acids with a concomitant increase in the index of stearoyl-CoA desaturase (SCD) in OCCC. We confirmed the upregulation of SCD (the rate-limiting enzyme for the synthesis of monounsaturated fatty acids) by immunohistochemistry (IHC) assays. Hence, by carrying out a mass spectrometry analysis of archival tissue samples, we were able to provide insights into lipidomic alterations in OCCC. [ABSTRACT FROM AUTHOR]
- Published
- 2021
- Full Text
- View/download PDF
37. Variability of Lipids in Human Milk.
- Author
-
Selvalatchmanan, Jayashree, Rukmini, A.V., Ji, Shanshan, Triebl, Alexander, Gao, Liang, Bendt, Anne K., Wenk, Markus R., Gooley, Joshua J., Torta, Federico, and Prehn, Cornelia
- Subjects
BREAST milk ,LIPIDS ,INFANT growth ,BIOLOGICAL variation ,MASS spectrometry ,MILKFAT ,LIPID metabolism ,CASEINS - Abstract
Lipids in breastmilk play a critical role in infant growth and development. However, few studies have investigated sources of variability of both high- and low-abundant milk lipids. The objective of our study was to investigate individual and morning–evening differences in the human milk lipidome. In this study, a modified two-phase method (MTBE: Methanol 7:2) was validated for the extraction of lipids from human breastmilk. This method was then applied to samples from a group of 20 healthy women to measure inter- and intra-individual (morning versus evening) variability of the breastmilk lipidome. We report here the levels of 237 lipid species from 13 sub-classes using reversed-phase liquid chromatography mass spectrometry (RP-LCMS) and direct-infusion mass spectrometry (DI-MS). About 85% of lipid species showed stable inter-individual differences across time points. Half of lipid species showed higher concentrations in the evening compared with the morning, with phosphatidylethanolamines (PEs) and triacylglycerols (TAGs) exhibiting the largest changes. In morning and evening samples, the biological variation was greater for diacylglycerols (DAGs) and TAGs compared with phospholipids and sphingolipids, and the variation in DAGs and TAGs was greater in evening samples compared with morning samples. These results demonstrate that variation in the milk lipidome is strongly influenced by individual differences and time of day. [ABSTRACT FROM AUTHOR]
- Published
- 2021
- Full Text
- View/download PDF
38. Placental 13C-DHA metabolism and relationship with maternal BMI, glycemia and birthweight.
- Author
-
Watkins, Oliver C., Selvam, Preben, Appukuttan Pillai, Reshma, Cracknell-Hazra, Victoria K. B., Yong, Hannah E. J., Sharma, Neha, Cazenave-Gassiot, Amaury, Bendt, Anne K., Godfrey, Keith M., Lewis, Rohan M., Wenk, Markus R., and Chan, Shiao-Yng
- Subjects
- *
HYPERGLYCEMIA , *BIRTH weight , *LIPID metabolism , *METABOLISM , *DOCOSAHEXAENOIC acid , *FETAL development - Abstract
Background: Fetal docosahexaenoic acid (DHA) supply relies on preferential transplacental transfer, which is regulated by placental DHA lipid metabolism. Maternal hyperglycemia and obesity associate with higher birthweight and fetal DHA insufficiency but the role of placental DHA metabolism is unclear. Methods: Explants from 17 term placenta were incubated with 13C-labeled DHA for 48 h, at 5 or 10 mmol/L glucose treatment, and the production of 17 individual newly synthesized 13C-DHA labeled lipids quantified by liquid chromatography mass spectrometry. Results: Maternal BMI positively associated with 13C-DHA-labeled diacylglycerols, triacylglycerols, lysophospholipids, phosphatidylcholine and phosphatidylethanolamine plasmalogens, while maternal fasting glycemia positively associated with five 13C-DHA triacylglycerols. In turn, 13C-DHA-labeled phospholipids and triacylglycerols positively associated with birthweight centile. In-vitro glucose treatment increased most 13C-DHA-lipids, but decreased 13C-DHA phosphatidylethanolamine plasmalogens. However, with increasing maternal BMI, the magnitude of the glucose treatment induced increase in 13C-DHA phosphatidylcholine and 13C-DHA lysophospholipids was curtailed, with further decline in 13C-DHA phosphatidylethanolamine plasmalogens. Conversely, with increasing birthweight centile glucose treatment induced increases in 13C-DHA triacylglycerols were exaggerated, while glucose treatment induced decreases in 13C-DHA phosphatidylethanolamine plasmalogens were diminished. Conclusions: Maternal BMI and glycemia increased the production of different placental DHA lipids implying impact on different metabolic pathways. Glucose-induced elevation in placental DHA metabolism is moderated with higher maternal BMI. In turn, findings of associations between many DHA lipids with birthweight suggest that BMI and glycemia promote fetal growth partly through changes in placental DHA metabolism. [ABSTRACT FROM AUTHOR]
- Published
- 2021
- Full Text
- View/download PDF
39. Triacylglycerol Utilization Is Required for Regrowth of In Vitro Hypoxic Nonreplicating Mycobacterium bovis Bacillus Calmette-Guerin.
- Author
-
Kai Leng Low, Rao, P. S. Srinivasa, Guanghou Shui, Bendt, Anne K., Pethe, Kevin, Dick, Thomas, and Wenk, Markus R.
- Subjects
- *
MYCOBACTERIUM bovis , *BACILLUS (Bacteria) , *BCG vaccines , *LIPIDS , *RESUSCITATION , *HYPOXEMIA , *ACTINOMYCETALES , *CHROMATOGRAPHIC analysis , *CRITICAL care medicine - Abstract
Mycobacteria store triacylglycerols (TGs) under various stress conditions, such as hypoxia, exposure to nitric oxide, and acidic environments. These stress conditions are known to induce nonreplicating persistence in mycobacteria. The importance of TG accumulation and utilization during regrowth is not clearly understood. Here we specifically determined the levels of accumulated TG and TG lipase activity in Mycobacterium bovis bacillus Calmette-Guerin (BCG) in various different physiological states (logarithmic growth, aerated stationary phase, hypoxia-induced dormancy, and regrowth from dormancy). We found extensive accumulation and degradation of TGs in the bacilli during entry into and exit from hypoxia-induced dormancy, respectively. These processes are accompanied by dynamic appearance and disappearance of intracellular TG lipid particles. The reduction in TG levels coincides with an increase in cellular TG lipase activity in the regrowing bacilli. Tetrahydrolipstatin, an inhibitor of TG lipases, reduces total lipase activity, prevents breakdown of TGs, and blocks the growth of mycobacteria upon resuscitation with air. Our results demonstrate that utilization of TGs is essential for the regrowth of mycobacteria during their exit from the hypoxic nonreplicating state. [ABSTRACT FROM AUTHOR]
- Published
- 2009
- Full Text
- View/download PDF
40. Association of acylcarnitines with maternal cardiometabolic risk factors is defined by chain length: the S-PRESTO study.
- Author
-
Chen L, Goh XP, Bendt AK, Tan KM, Leow MK, Tan KH, Chan JKY, Chan SY, Chong YS, Gluckman PD, Eriksson JG, Wenk MR, and Mir SA
- Abstract
Context: Due to the essential role of carnitine as an intermediary in amino acid, carbohydrate and lipid metabolism, a detailed characterization of circulating and urinary carnitine concentrations will aid in elucidating the molecular basis of impaired maternal metabolic flexibility and facilitating timely intervention for expectant mothers., Objective: To investigate the association of maternal plasma and urinary free carnitine and acylcarnitines with cardiometabolic risk factors., Methods: LC-MS/MS-based quantification of free carnitine and acylcarnitines (C2-C18) was performed on 765 plasma and 702 urine samples collected at preconception, 26-28 weeks' pregnancy, and three months postpartum in the Singapore PREconception Study of long-Term maternal and child Outcomes (S-PRESTO) cohort study., Results: Plasma concentrations of free carnitine and acylcarnitines decreased coupled with increased renal clearance in pregnancy compared to preconception and postpartum. Renal clearance of carnitine increased with an increase in pre-pregnancy body mass index (ppBMI) and gestational weight gain. Plasma short-chain acylcarnitines were positively associated with ppBMI, irrespective of the physiological state, while medium- and long-chain acylcarnitines were negatively associated with ppBMI at preconception and postpartum but showed a positive association in pregnancy. Similarly, plasma short-chain acylcarnitines were positively associated with HOMA-IR whereas medium- and long-chain acylcarnitines were negatively associated with HOMA-IR at preconception and in pregnancy. Mothers who developed gestational diabetes mellitus during pregnancy had ∼10% higher plasma propionylcarnitine concentration and ∼18% higher urine tiglylcarnitine concentration compared to mothers with normal glucose metabolism at preconception., Conclusions: This study provides the metabolic and physiological basis of maternal carnitine homeostasis, which can be used in assessment of maternal cardiometabolic health at preconception to improve pregnancy outcomes., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)
- Published
- 2024
- Full Text
- View/download PDF
41. Increasing maternal age associates with lower placental CPT1B mRNA expression and acylcarnitines, particularly in overweight women.
- Author
-
Yong HEJ, Watkins OC, Mah TKL, Cracknell-Hazra VKB, Pillai RA, Selvam P, Islam MO, Sharma N, Cazenave-Gassiot A, Bendt AK, Wenk MR, Godfrey KM, Lewis RM, and Chan SY
- Abstract
Older pregnant women have increased risks of complications including gestational diabetes and stillbirth. Carnitine palmitoyl transferase (CPT) expression declines with age in several tissues and is linked with poorer metabolic health. Mitochondrial CPTs catalyze acylcarnitine synthesis, which facilitates fatty acid oxidization as fuel. We hypothesized that the placenta, containing maternally-inherited mitochondria, shows an age-related CPT decline that lowers placental acylcarnitine synthesis, increasing vulnerability to pregnancy complications. We assessed CPT1A , CPT1B , CPT1C and CPT2 mRNA expression by qPCR in 77 placentas and quantified 10 medium and long-chain acylcarnitines by LC-MS/MS in a subset of 50 placentas. Older maternal age associated with lower expression of placental CPT1B , but not CPT1A , CPT1C or CPT2 . CPT1B expression positively associated with eight acylcarnitines and CPT1C with three acylcarnitines, CPT1A negatively associated with nine acylcarnitines, while CPT2 did not associate with any acylcarnitine. Older maternal age associated with reductions in five acylcarnitines, only in those with BMI≥ 25 kg/m
2 , and not after adjusting for CPT1B expression. Our findings suggest that CPT1B is the main transferase for placental long-chain acylcarnitine synthesis, and age-related CPT1B decline may underlie decreased placental metabolic flexibility, potentially contributing to pregnancy complications in older women, particularly if they are overweight., Competing Interests: S-YC and KG are part of an academic consortium that has received research funding from Société Des Produits Nestlé S.A. and BenevolentAI Bio Ltd for work unrelated to this manuscript. S-YC and KMG are co-inventors on patent filings by Nestlé S.A. which covers the use of inositol in human health applications, but which do not draw on the work in this manuscript. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Yong, Watkins, Mah, Cracknell-Hazra, Pillai, Selvam, Islam, Sharma, Cazenave-Gassiot, Bendt, Wenk, Godfrey, Lewis and Chan.)- Published
- 2023
- Full Text
- View/download PDF
42. Myo-inositol alters 13C-labeled fatty acid metabolism in human placental explants.
- Author
-
Watkins OC, Islam MO, Selvam P, Pillai RA, Cazenave-Gassiot A, Bendt AK, Karnani N, Godfrey KM, Lewis RM, Wenk MR, and Chan SY
- Abstract
We postulate that myo-inositol, a proposed intervention for gestational-diabetes, affects transplacental lipid supply to the fetus. We investigated the effect of myo-inositol on fatty-acid processing in human placental-explants from uncomplicated pregnancies. Explants were incubated with 13C-labeled palmitic-acid, 13C-oleic-acid and 13C-docosahexaenoic-acid across a range of myo-inositol concentrations for 24 h and 48 h. The incorporation of labeled-fatty-acids into individual lipids was quantified by liquid-chromatography-mass-spectrometry. At 24 h, myo-inositol increased the amount of 13C-palmitic-acid and 13C-oleic-acid labeled lipids (median fold-change relative to control=1). Significant effects were seen with 30 µM myo-inositol (physiological) for 13C-palmitic-acid-lysophosphatidylcholines (1.26) and 13C-palmitic-acid-phosphatidylethanolamines (1.17). At 48 h, myo-inositol addition increased 13C-oleic-acid-lipids but decreased 13C-palmitic-acid and 13C-docosahexaenoic-acid lipids. Significant effects were seen with 30 µM myo-inositol for 13C-oleic-acid-phosphatidylcholines (1.25), 13C-oleic-acid-phosphatidylethanolamines (1.37) and 13C-oleic-acid-triacylglycerols (1.32) and with 100 µM myo-inositol for 13C-docosahexaenoic-acid-triacylglycerols (0.78). Lipids labeled with the same 13C-fatty-acid showed similar responses when tested at the same time-point, suggesting myo-inositol alters upstream processes such as fatty-acid uptake or activation. Myo-inositol supplementation may alter placental lipid physiology with unknown clinical consequences.
- Published
- 2019
- Full Text
- View/download PDF
43. Metabolism of 13C-Labeled Fatty Acids in Term Human Placental Explants by Liquid Chromatography-Mass Spectrometry.
- Author
-
Watkins OC, Islam MO, Selvam P, Pillai RA, Cazenave-Gassiot A, Bendt AK, Karnani N, Godfrey KM, Lewis RM, Wenk MR, and Chan SY
- Subjects
- Adult, Body Mass Index, Carbon Isotopes, Chromatography, Liquid, Female, Humans, Mass Spectrometry, Pregnancy, Fatty Acids metabolism, Lipid Metabolism physiology, Placenta metabolism
- Abstract
Placental lipid transport and metabolism are poorly understood despite the importance for fetal development and lifelong health. We aimed to explore fatty acid (FA) processing in human villous placental explants from seven uncomplicated term singleton pregnancies delivered by elective cesarean section. Explants were treated with stable isotope-labeled palmitic acid (13C-PA), oleic acid (13C-OA), or docosahexaenoic acid (13C-DHA) for 3, 24, or 48 hours. Stable isotope-labeled lipids synthesized by placental explants from labeled FA were quantified, alongside endogenous unlabeled placental lipids, by liquid chromatography-mass spectrometry. Labeled phosphatidylcholines (PCs), triacylglycerols (TAGs), and phosphatidylethanolamines were detected in explants, whereas labeled lysophosphatidylcholines were found in both explants and conditioned media. 13C-PA was primarily directed into PC synthesis (74% of 13C-PA-labeled lipids), whereas 13C-OA was directed almost equally into PC and TAG synthesis (45% and 53%, respectively, of 13C-OA-labeled lipids). 13C-DHA was only detectable in TAGs. TAGs demonstrated the highest isotopic enrichment for all 13C-FAs with 13C-OA-TAGs comprising >50% of total OA-TAGs (unlabeled and labeled), consistent with TAGs being a labile and accessible reservoir for FA storage. Variations in lipid incorporation were correlated to maternal glycemia and body mass index, suggesting that this experimental model could be used to investigate the effect of maternal factors on placental lipid metabolism. We conclude that lipid metabolic partitioning of freshly imported FAs into labile and less labile lipid reservoirs in placenta is FA dependent. This process may partly mediate the physiological preferential transplacental transfer of particular FAs to the fetus, but may also be implicated in the fetoplacental pathophysiology of maternal metabolic dysfunction., (Copyright © 2019 Endocrine Society.)
- Published
- 2019
- Full Text
- View/download PDF
44. Novel phage display-derived mycolic acid-specific antibodies with potential for tuberculosis diagnosis.
- Author
-
Chan CE, Zhao BZ, Cazenave-Gassiot A, Pang SW, Bendt AK, Wenk MR, MacAry PA, and Hanson BJ
- Subjects
- Antibodies, Bacterial biosynthesis, Antibody Specificity, Biomarkers metabolism, Cell Surface Display Techniques, Enzyme-Linked Immunosorbent Assay, HEK293 Cells, Humans, Limit of Detection, Mycobacterium bovis metabolism, Mycobacterium smegmatis metabolism, Mycolic Acids isolation & purification, Mycolic Acids metabolism, Protein Binding, Tuberculosis, Pulmonary metabolism, Antibodies, Bacterial chemistry, Mycolic Acids immunology, Tuberculosis, Pulmonary diagnosis
- Abstract
Tuberculosis is a major cause of mortality and morbidity due to infectious disease. However, current clinical diagnostic methodologies such as PCR, sputum culture, or smear microscopy are not ideal. Antibody-based assays are a suitable alternative but require specific antibodies against a suitable biomarker. Mycolic acid, which has been found in patient sputum samples and comprises a large portion of the mycobacterial cell wall, is an ideal target. However, generating anti-lipid antibodies using traditional hybridoma methodologies is challenging and has limited the exploitation of this lipid as a diagnostic marker. We describe here the isolation and characterization of four anti-mycolic acid antibodies from a nonimmune antibody phage display library that can detect mycolic acids down to a limit of 4.5ng. All antibodies were specific for the methoxy subclass of mycolic acid with weak binding for α mycolic acid and did not show any binding to closely related lipids or other Mycobacterium tuberculosis (Mtb) derived lipids. We also determined the clinical utility of these antibodies based on their limit of detection for mycobacteria colony forming units (CFU). In combination with an optimized alkaline hydrolysis method for rapid lipid extraction, these antibodies can detect 10(5) CFU of Mycobacterium bovis BCG, a close relative of Mtb and therefore represent a novel approach for the development of diagnostic assays for lipid biomarkers.
- Published
- 2013
- Full Text
- View/download PDF
45. Structural and biological diversity of lipopolysaccharides from Burkholderia pseudomallei and Burkholderia thailandensis.
- Author
-
Novem V, Shui G, Wang D, Bendt AK, Sim SH, Liu Y, Thong TW, Sivalingam SP, Ooi EE, Wenk MR, and Tan G
- Subjects
- Animals, Burkholderia immunology, Burkholderia pseudomallei immunology, Burkholderia pseudomallei pathogenicity, Cell Line, Cytokines biosynthesis, Gas Chromatography-Mass Spectrometry, Humans, Immunity, Innate, Lipid A chemistry, Lipid A immunology, Lipopolysaccharides administration & dosage, Lipopolysaccharides immunology, Macrophages drug effects, Macrophages immunology, Mice, Molecular Structure, Species Specificity, Spectrometry, Mass, Electrospray Ionization, Tandem Mass Spectrometry, Toll-Like Receptor 4 agonists, Virulence immunology, Burkholderia chemistry, Burkholderia pseudomallei chemistry, Lipopolysaccharides chemistry
- Abstract
Burkholderia pseudomallei, the etiological agent of melioidosis, is a facultative intracellular pathogen. As B. pseudomallei is a gram-negative bacterium, its outer membrane contains lipopolysaccharide (LPS) molecules, which have been shown to have low-level immunological activities in vitro. In this study, the biological activities of B. pseudomallei LPS were compared to those of Burkholderia thailandensis LPS, and it was found that both murine and human macrophages produced levels of tumor necrosis factor alpha, interleukin-6 (IL-6), and IL-10 in response to B. pseudomallei LPS that were lower than those in response to B. thailandensis LPS in vitro. In order to elucidate the molecular mechanisms underlying the low-level immunological activities of B. pseudomallei LPS, its lipid A moiety was characterized using mass spectrometry. The major lipid A species identified in B. pseudomallei consists of a biphosphorylated disaccharide backbone, which is modified with 4-amino-4-deoxy-arabinose (Ara4N) at both phosphates and penta-acylated with fatty acids (FA) C(14:0)(3-OH), C(16:0)(3-OH), and either C(14:0) or C(14:0)(2-OH). In contrast, the major lipid A species identified in B. thailandensis was a mixture of tetra- and penta-acylated structures with differing amounts of Ara4N and FA C(14:0)(3-OH). Lipid A species acylated with FA C(14:0)(2-OH) were unique to B. pseudomallei and not found in B. thailandensis. Our data thus indicate that B. pseudomallei synthesizes lipid A species with long-chain FA C(14:0)(2-OH) and Ara4N-modified phosphate groups, allowing it to evade innate immune recognition.
- Published
- 2009
- Full Text
- View/download PDF
46. Sensitive profiling of chemically diverse bioactive lipids.
- Author
-
Shui G, Bendt AK, Pethe K, Dick T, and Wenk MR
- Subjects
- Chromatography, High Pressure Liquid methods, Mycobacterium bovis chemistry, Mycobacterium tuberculosis chemistry, Sensitivity and Specificity, Spectrometry, Mass, Electrospray Ionization methods, Lipids chemistry, Mycolic Acids chemistry
- Abstract
Here, we present an improved method for sensitive profiling of lipids in a single high-performance liquid chromatography-electrospray ionization-quadrupole time of flight mass spectrometry experiment. The approach consists of i) sensitive isocratic elution, which takes advantage of C18 column material that is resistant to increased pH values induced by piperidine, ii) chemometric alignment of mass spectra followed by differential analysis of ion intensities, and iii) semiquantitative analysis of extracted ion chromatograms of interest. A key advantage of this method is its wide applicability to extracts that harbor lipids of considerable chemical complexity. The method allows qualitative and semiquantitative analysis of fatty acyls, glycerophospholipids (such as glycerophosphatidylinositols, glycerophosphatidylserines, and glycerophosphatidylcholines in brain extracts), phosphatidylinositol mannosides, acylated glycerophospholipids, sphingolipids (including ceramides and gangliosides in brain extracts), and, for the first time with ESI, prenols and mycolic acids (MAs). MAs are targets in antimycobacterial therapy, and they play an important immunomodulatory role during host-pathogen interactions. We compared high-resolution mass spectra of MAs derived from Mycobacterium bovis Bacille Camette-Guérin during entry into nonreplicative conditions induced by oxygen deprivation (hypoxic dormancy). Although the overall composition is not drastically altered, there are pronounced differences in individual MAs. alpha-MAs accumulate during entry into dormancy, whereas a subpopulation of keto-MAs is almost entirely eliminated. This effect is reversed upon resuscitation of dormant mycobacteria. These results provide detailed chemical information with relevance to drug development and immunobiology of mycobacteria.
- Published
- 2007
- Full Text
- View/download PDF
47. Towards a phosphoproteome map of Corynebacterium glutamicum.
- Author
-
Bendt AK, Burkovski A, Schaffer S, Bott M, Farwick M, and Hermann T
- Subjects
- Electrophoresis, Gel, Two-Dimensional, Corynebacterium metabolism, Phosphoproteins metabolism, Proteome
- Abstract
In this study, the phosphoproteome of Corynebacterium glutamicum, an industrially important soil bacterium of the Corynebacterium/Mycobacterium/Nocardia (CMN) group of Gram-positive bacteria, was investigated by two different detection methods: first, by in vivo radio-labeling using [(33)P]-phosphoric acid with subsequent autoradiography and second, by immunostaining with phosphoamino acid-specific monoclonal antibodies. After two-dimensional gel electrophoresis (2-DE), around 60 [(33)P]-labeled protein spots were visualized and around 90 antibody-decorated protein spots detected; 31 of the protein spots were detected with both methods. By peptide mass fingerprinting, 41 different proteins were identified, namely 5-enolpyruvylshikimate 3-phosphate synthase, aconitase, acyl-CoA carboxylase, acyl-CoA synthetase, ATP (synthase alpha- and beta-chain), carbamoyl-phosphate synthase, citrate synthase, cysteine synthase, DnaK, the elongation factors G, P, Ts and Tu, enolase, fructose bisphosphate aldolase, fumarase, Gap dehydrogenase, glutamine synthetase I, glycine hydroxymethyltransferase, GroEL2, GTPase, heat-inducible transcriptional repressor DnaJ2, inorganic pyrophosphatase, isocitrate dehydrogenase, ketol-acid reductoisomerase, lactate dehydrogenase, leucine-tRNA ligase, lipoamide dehydrogenase, methionine synthase, O-acetylhomoserine sulfhydrylase, pyruvate carboxylase, pyruvate kinase, pyruvate oxidase, ribosomal protein S1, RNA polymerase (beta-subunit), succinyl-CoA:CoA transferase, transketolase and UDP-N-acetylmuramoyl-L-alanine ligase, besides a hypothetical 35k protein and a hypothetical glucose kinase. Both detection techniques were used to create a phosphoproteome map. Additionally, the influence of nitrogen deprivation on the phosphoproteome of C. glutamicum was investigated.
- Published
- 2003
- Full Text
- View/download PDF
Catalog
Discovery Service for Jio Institute Digital Library
For full access to our library's resources, please sign in.