Untargeted Plasma Metabolomics Unravels a Metabolic Signature for Tissue Sensitivity to Glucocorticoids in Healthy Subjects: Its Implications in Dietary Planning for a Healthy Lifestyle
In clinical practice, differences in glucocorticoid sensitivity among healthy subjects may influence the outcome and any adverse effects of glucocorticoid therapy. Thus, a fast and accurate methodology that could enable the classification of individuals based on their tissue glucocorticoid sensitivi...
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MDPI AG
2021-06-01
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| Series: | Nutrients |
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| Online Access: | https://www.mdpi.com/2072-6643/13/6/2120 |
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| author | Nicolas C. Nicolaides Maria-Konstantina Ioannidi Eleni Koniari Ifigeneia Papageorgiou Anastasia Bartzeliotou Amalia Sertedaki Maria I. Klapa Evangelia Charmandari |
| author_facet | Nicolas C. Nicolaides Maria-Konstantina Ioannidi Eleni Koniari Ifigeneia Papageorgiou Anastasia Bartzeliotou Amalia Sertedaki Maria I. Klapa Evangelia Charmandari |
| author_sort | Nicolas C. Nicolaides |
| collection | DOAJ |
| description | In clinical practice, differences in glucocorticoid sensitivity among healthy subjects may influence the outcome and any adverse effects of glucocorticoid therapy. Thus, a fast and accurate methodology that could enable the classification of individuals based on their tissue glucocorticoid sensitivity would be of value. We investigated the usefulness of untargeted plasma metabolomics in identifying a panel of metabolites to distinguish glucocorticoid-resistant from glucocorticoid-sensitive healthy subjects who do not carry mutations in the human glucocorticoid receptor (<i>NR3C1</i>) gene. Applying a published methodology designed for the study of glucocorticoid sensitivity in healthy adults, 101 healthy subjects were ranked according to their tissue glucocorticoid sensitivity based on 8:00 a.m. serum cortisol concentrations following a very low-dose dexamethasone suppression test. Ten percent of the cohort, i.e., 11 participants, on each side of the ranking, with no <i>NR3C1</i> mutations or polymorphisms, were selected, respectively, as the most glucocorticoid-sensitive and most glucocorticoid-resistant of the cohort to be analyzed and compared with untargeted blood plasma metabolomics using gas chromatography–mass spectrometry (GC–MS). The acquired metabolic profiles were evaluated using multivariate statistical analysis methods. Nineteen metabolites were identified with significantly lower abundance in the most sensitive compared to the most resistant group of the cohort, including fatty acids, sugar alcohols, and serine/threonine metabolism intermediates. These results, combined with a higher glucose, sorbitol, and lactate abundance, suggest a higher Cori cycle, polyol pathway, and inter-tissue one-carbon metabolism rate and a lower fat mobilization rate at the fasting state in the most sensitive compared to the most resistant group. In fact, this was the first study correlating tissue glucocorticoid sensitivity with serine/threonine metabolism. Overall, the observed metabolic signature in this cohort implies a worse cardiometabolic profile in the most glucocorticoid-sensitive compared to the most glucocorticoid-resistant healthy subjects. These findings offer a metabolic signature that distinguishes most glucocorticoid-sensitive from most glucocorticoid-resistant healthy subjects to be further validated in larger cohorts. Moreover, they support the correlation of tissue glucocorticoid sensitivity with insulin resistance and metabolic syndrome-associated pathways, further emphasizing the need for nutritionists and doctors to consider the tissue glucocorticoid sensitivity in dietary and exercise planning, particularly when these subjects are to be treated with glucocorticoids. |
| first_indexed | 2024-03-10T10:14:06Z |
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| institution | Directory Open Access Journal |
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| language | English |
| last_indexed | 2024-03-10T10:14:06Z |
| publishDate | 2021-06-01 |
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| series | Nutrients |
| spelling | doaj.art-db59e0d713f04d908b4e1b88983f4bf02023-11-22T00:59:17ZengMDPI AGNutrients2072-66432021-06-01136212010.3390/nu13062120Untargeted Plasma Metabolomics Unravels a Metabolic Signature for Tissue Sensitivity to Glucocorticoids in Healthy Subjects: Its Implications in Dietary Planning for a Healthy LifestyleNicolas C. Nicolaides0Maria-Konstantina Ioannidi1Eleni Koniari2Ifigeneia Papageorgiou3Anastasia Bartzeliotou4Amalia Sertedaki5Maria I. Klapa6Evangelia Charmandari7Division of Endocrinology, Metabolism and Diabetes, First Department of Pediatrics, Νational and Kapodistrian University of Athens Medical School, ‘Aghia Sophia’ Children’s Hospital, 11527 Athens, GreeceMetabolic Engineering and Systems Biology Laboratory, Institute of Chemical Engineering Sciences, Foundation for Research and Technology-Hellas (FORTH/ICE-HT), 26504 Patras, GreeceDivision of Endocrinology, Metabolism and Diabetes, First Department of Pediatrics, Νational and Kapodistrian University of Athens Medical School, ‘Aghia Sophia’ Children’s Hospital, 11527 Athens, GreeceDivision of Endocrinology, Metabolism and Diabetes, First Department of Pediatrics, Νational and Kapodistrian University of Athens Medical School, ‘Aghia Sophia’ Children’s Hospital, 11527 Athens, GreeceDepartment of Clinical Biochemistry, Νational and Kapodistrian University of Athens Medical School, ‘Aghia Sophia’ Children’s Hospital, 11527 Athens, GreeceDivision of Endocrinology, Metabolism and Diabetes, First Department of Pediatrics, Νational and Kapodistrian University of Athens Medical School, ‘Aghia Sophia’ Children’s Hospital, 11527 Athens, GreeceMetabolic Engineering and Systems Biology Laboratory, Institute of Chemical Engineering Sciences, Foundation for Research and Technology-Hellas (FORTH/ICE-HT), 26504 Patras, GreeceDivision of Endocrinology, Metabolism and Diabetes, First Department of Pediatrics, Νational and Kapodistrian University of Athens Medical School, ‘Aghia Sophia’ Children’s Hospital, 11527 Athens, GreeceIn clinical practice, differences in glucocorticoid sensitivity among healthy subjects may influence the outcome and any adverse effects of glucocorticoid therapy. Thus, a fast and accurate methodology that could enable the classification of individuals based on their tissue glucocorticoid sensitivity would be of value. We investigated the usefulness of untargeted plasma metabolomics in identifying a panel of metabolites to distinguish glucocorticoid-resistant from glucocorticoid-sensitive healthy subjects who do not carry mutations in the human glucocorticoid receptor (<i>NR3C1</i>) gene. Applying a published methodology designed for the study of glucocorticoid sensitivity in healthy adults, 101 healthy subjects were ranked according to their tissue glucocorticoid sensitivity based on 8:00 a.m. serum cortisol concentrations following a very low-dose dexamethasone suppression test. Ten percent of the cohort, i.e., 11 participants, on each side of the ranking, with no <i>NR3C1</i> mutations or polymorphisms, were selected, respectively, as the most glucocorticoid-sensitive and most glucocorticoid-resistant of the cohort to be analyzed and compared with untargeted blood plasma metabolomics using gas chromatography–mass spectrometry (GC–MS). The acquired metabolic profiles were evaluated using multivariate statistical analysis methods. Nineteen metabolites were identified with significantly lower abundance in the most sensitive compared to the most resistant group of the cohort, including fatty acids, sugar alcohols, and serine/threonine metabolism intermediates. These results, combined with a higher glucose, sorbitol, and lactate abundance, suggest a higher Cori cycle, polyol pathway, and inter-tissue one-carbon metabolism rate and a lower fat mobilization rate at the fasting state in the most sensitive compared to the most resistant group. In fact, this was the first study correlating tissue glucocorticoid sensitivity with serine/threonine metabolism. Overall, the observed metabolic signature in this cohort implies a worse cardiometabolic profile in the most glucocorticoid-sensitive compared to the most glucocorticoid-resistant healthy subjects. These findings offer a metabolic signature that distinguishes most glucocorticoid-sensitive from most glucocorticoid-resistant healthy subjects to be further validated in larger cohorts. Moreover, they support the correlation of tissue glucocorticoid sensitivity with insulin resistance and metabolic syndrome-associated pathways, further emphasizing the need for nutritionists and doctors to consider the tissue glucocorticoid sensitivity in dietary and exercise planning, particularly when these subjects are to be treated with glucocorticoids.https://www.mdpi.com/2072-6643/13/6/2120tissue glucocorticoid sensitivity in healthy adultsdietary planningglucocorticoid receptoruntargeted GC–MS metabolomicsblood plasma metabolic signatureprecision medicine |
| spellingShingle | Nicolas C. Nicolaides Maria-Konstantina Ioannidi Eleni Koniari Ifigeneia Papageorgiou Anastasia Bartzeliotou Amalia Sertedaki Maria I. Klapa Evangelia Charmandari Untargeted Plasma Metabolomics Unravels a Metabolic Signature for Tissue Sensitivity to Glucocorticoids in Healthy Subjects: Its Implications in Dietary Planning for a Healthy Lifestyle Nutrients tissue glucocorticoid sensitivity in healthy adults dietary planning glucocorticoid receptor untargeted GC–MS metabolomics blood plasma metabolic signature precision medicine |
| title | Untargeted Plasma Metabolomics Unravels a Metabolic Signature for Tissue Sensitivity to Glucocorticoids in Healthy Subjects: Its Implications in Dietary Planning for a Healthy Lifestyle |
| title_full | Untargeted Plasma Metabolomics Unravels a Metabolic Signature for Tissue Sensitivity to Glucocorticoids in Healthy Subjects: Its Implications in Dietary Planning for a Healthy Lifestyle |
| title_fullStr | Untargeted Plasma Metabolomics Unravels a Metabolic Signature for Tissue Sensitivity to Glucocorticoids in Healthy Subjects: Its Implications in Dietary Planning for a Healthy Lifestyle |
| title_full_unstemmed | Untargeted Plasma Metabolomics Unravels a Metabolic Signature for Tissue Sensitivity to Glucocorticoids in Healthy Subjects: Its Implications in Dietary Planning for a Healthy Lifestyle |
| title_short | Untargeted Plasma Metabolomics Unravels a Metabolic Signature for Tissue Sensitivity to Glucocorticoids in Healthy Subjects: Its Implications in Dietary Planning for a Healthy Lifestyle |
| title_sort | untargeted plasma metabolomics unravels a metabolic signature for tissue sensitivity to glucocorticoids in healthy subjects its implications in dietary planning for a healthy lifestyle |
| topic | tissue glucocorticoid sensitivity in healthy adults dietary planning glucocorticoid receptor untargeted GC–MS metabolomics blood plasma metabolic signature precision medicine |
| url | https://www.mdpi.com/2072-6643/13/6/2120 |
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