{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,17]],"date-time":"2025-11-17T21:31:13Z","timestamp":1763415073753,"version":"build-2065373602"},"reference-count":59,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2021,6,21]],"date-time":"2021-06-21T00:00:00Z","timestamp":1624233600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"The clinical study has been co-financed by the European Regional Development Fund of the European Union and Greek national funds through the Operational Program Competitiveness, Entrepreneurship and Innovation, under the call RESEARCH \u2013 CREATE \u2013 INNOVATE","award":["(project code: T1EDK-01386, MIS: 5030543, Acronym: PEDOBESITY)"],"award-info":[{"award-number":["(project code: T1EDK-01386, MIS: 5030543, Acronym: PEDOBESITY)"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Nutrients"],"abstract":"<jats:p>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 (NR3C1) 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 NR3C1 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\u2013mass spectrometry (GC\u2013MS). 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.<\/jats:p>","DOI":"10.3390\/nu13062120","type":"journal-article","created":{"date-parts":[[2021,6,21]],"date-time":"2021-06-21T04:21:21Z","timestamp":1624249281000},"page":"2120","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"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"],"prefix":"10.3390","volume":"13","author":[{"given":"Nicolas C.","family":"Nicolaides","sequence":"first","affiliation":[{"name":"Division of Endocrinology, Metabolism and Diabetes, First Department of Pediatrics, \u039dational and Kapodistrian University of Athens Medical School, \u2018Aghia Sophia\u2019 Children\u2019s Hospital, 11527 Athens, Greece"},{"name":"Division of Endocrinology and Metabolism, Center for Clinical, Experimental Surgery and Translational Research, Biomedical Research Foundation of the Academy of Athens, 11528 Athens, Greece"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7914-8363","authenticated-orcid":false,"given":"Maria-Konstantina","family":"Ioannidi","sequence":"additional","affiliation":[{"name":"Metabolic Engineering and Systems Biology Laboratory, Institute of Chemical Engineering Sciences, Foundation for Research and Technology-Hellas (FORTH\/ICE-HT), 26504 Patras, Greece"},{"name":"Department of Biology, University of Patras, 26500 Patras, Greece"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Eleni","family":"Koniari","sequence":"additional","affiliation":[{"name":"Division of Endocrinology, Metabolism and Diabetes, First Department of Pediatrics, \u039dational and Kapodistrian University of Athens Medical School, \u2018Aghia Sophia\u2019 Children\u2019s Hospital, 11527 Athens, Greece"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ifigeneia","family":"Papageorgiou","sequence":"additional","affiliation":[{"name":"Division of Endocrinology, Metabolism and Diabetes, First Department of Pediatrics, \u039dational and Kapodistrian University of Athens Medical School, \u2018Aghia Sophia\u2019 Children\u2019s Hospital, 11527 Athens, Greece"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anastasia","family":"Bartzeliotou","sequence":"additional","affiliation":[{"name":"Department of Clinical Biochemistry, \u039dational and Kapodistrian University of Athens Medical School, \u2018Aghia Sophia\u2019 Children\u2019s Hospital, 11527 Athens, Greece"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Amalia","family":"Sertedaki","sequence":"additional","affiliation":[{"name":"Division of Endocrinology, Metabolism and Diabetes, First Department of Pediatrics, \u039dational and Kapodistrian University of Athens Medical School, \u2018Aghia Sophia\u2019 Children\u2019s Hospital, 11527 Athens, Greece"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2047-3185","authenticated-orcid":false,"given":"Maria I.","family":"Klapa","sequence":"additional","affiliation":[{"name":"Metabolic Engineering and Systems Biology Laboratory, Institute of Chemical Engineering Sciences, Foundation for Research and Technology-Hellas (FORTH\/ICE-HT), 26504 Patras, Greece"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0851-6998","authenticated-orcid":false,"given":"Evangelia","family":"Charmandari","sequence":"additional","affiliation":[{"name":"Division of Endocrinology, Metabolism and Diabetes, First Department of Pediatrics, \u039dational and Kapodistrian University of Athens Medical School, \u2018Aghia Sophia\u2019 Children\u2019s Hospital, 11527 Athens, Greece"},{"name":"Division of Endocrinology and Metabolism, Center for Clinical, Experimental Surgery and Translational Research, Biomedical Research Foundation of the Academy of Athens, 11528 Athens, Greece"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2021,6,21]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1111\/nyas.12464","article-title":"Circadian endocrine rhythms: The hypothalamic-pituitary-adrenal axis and its actions","volume":"1318","author":"Nicolaides","year":"2014","journal-title":"Ann. N. Y. Acad. Sci."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"70","DOI":"10.3389\/fendo.2017.00070","article-title":"Stress-related and circadian secretion and target tissue actions of glucocorticoids: Impact on health","volume":"8","author":"Nicolaides","year":"2017","journal-title":"Front. Endocrinol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.steroids.2009.09.002","article-title":"The human glucocorticoid receptor: Molecular basis of biologic function","volume":"75","author":"Nicolaides","year":"2010","journal-title":"Steroids"},{"key":"ref_4","first-page":"124","article-title":"Novel insights into the molecular mechanisms underlying generalized glucocorticoid resistance and hypersensitivity syndromes","volume":"16","author":"Nicolaides","year":"2017","journal-title":"Hormones"},{"key":"ref_5","first-page":"pe48","article-title":"Intracellular Glucocorticoid Signaling: A Formerly Simple System Turns Stochastic","volume":"2005","author":"Chrousos","year":"2005","journal-title":"Sci. Signal."},{"key":"ref_6","first-page":"3","article-title":"The Role of S-Palmitoylation of the Human Glucocorticoid Receptor (hGR) in Mediating the Nongenomic Glucocorticoid Actions","volume":"6","author":"Nicolaides","year":"2017","journal-title":"J. Mol. Biochem."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1711","DOI":"10.1056\/NEJMra050541","article-title":"Anti-inflammatory Action of Glucocorticoids\u2014New Mechanisms for Old Drugs","volume":"353","author":"Rhen","year":"2005","journal-title":"N. Engl. J. Med."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"670","DOI":"10.1038\/nrendo.2013.183","article-title":"Glucocorticoid sensitivity in health and disease","volume":"9","author":"Quax","year":"2013","journal-title":"Nat. Rev. Endocrinol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"545","DOI":"10.1016\/j.beem.2015.04.007","article-title":"Specificity and sensitivity of glucocorticoid signaling in health and disease","volume":"29","author":"Cain","year":"2015","journal-title":"Best Pract. Res. Clin. Endocrinol. Metab."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"331","DOI":"10.1016\/j.molcel.2005.03.025","article-title":"Translational regulatory mechanisms generate N-terminal glucocorticoid receptor isoforms with unique transcriptional target genes","volume":"18","author":"Lu","year":"2005","journal-title":"Mol. Cell"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1005","DOI":"10.1007\/s00432-017-2388-4","article-title":"The effects of microRNAs on glucocorticoid responsiveness","volume":"143","author":"Wang","year":"2017","journal-title":"J. Cancer Res. Clin. Oncol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"94","DOI":"10.2174\/1566524015666150114122354","article-title":"Long Noncoding RNA GAS5: A Novel Marker Involved in Glucocorticoid Response","volume":"15","author":"Silvestre","year":"2015","journal-title":"Curr. Mol. Med."},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Dunford, E.C., and Riddell, M.C. (2016). The Metabolic Implications of Glucocorticoids in a High-Fat Diet Setting and the Counter-Effects of Exercise. Metabolites, 6.","DOI":"10.3390\/metabo6040044"},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Van der Lugt, T., Weseler, A.R., Vrolijk, M.F., Opperhuizen, A., and Bast, A. (2020). Dietary advanced glycation endproducts decrease glucocorticoid sensitivity in vitro. Nutrients, 12.","DOI":"10.3390\/nu12020441"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"692","DOI":"10.1038\/nbt823","article-title":"High-throughput classification of yeast mutants for functional genomics using metabolic footprinting","volume":"21","author":"Allen","year":"2003","journal-title":"Nat. Biotechnol."},{"key":"ref_16","unstructured":"Giera, M., Spilker, M.E., and Siuzdak, G. Metabolomics: The Superglue of Omics. Fields and Applications: Metabolomics & Lipidomics. 2 December 2018. Available online: https:\/\/theanalyticalscientist.com\/fields-applications\/metabolomics-the-superglue-of-omics."},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Gkourogianni, A., Kosteria, I., Telonis, A.G., Margeli, A., Mantzou, E., Konsta, M., Loutradis, D., Mastorakos, G., Papassotiriou, I., and Klapa, M.I. (2014). Plasma metabolomic profiling suggests early indications for predisposition to latent insulin resistance in children conceived by ICSI. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0094001"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"183","DOI":"10.1146\/annurev-nutr-072610-145159","article-title":"Nutritional metabolomics: Progress in addressing complexity in diet and health","volume":"32","author":"Jones","year":"2012","journal-title":"Annu. Rev. Nutr."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"191","DOI":"10.1016\/j.jchromb.2008.04.049","article-title":"Standardizing GC-MS metabolomics","volume":"871","author":"Kanani","year":"2008","journal-title":"J. Chromatogr. B Anal. Technol. Biomed. Life Sci."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"402","DOI":"10.1096\/fj.06-7236com","article-title":"Use of gene expression profiling to identify a novel glucocorticoid sensitivity determining gene, BMPRII","volume":"21","author":"Donn","year":"2007","journal-title":"FASEB J."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"e13129","DOI":"10.1111\/eci.13129","article-title":"Transcriptomics in tissue glucocorticoid sensitivity","volume":"49","author":"Nicolaides","year":"2019","journal-title":"Eur. J. Clin. Investig."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1016\/j.ymben.2006.08.001","article-title":"Data correction strategy for metabolomics analysis using gas chromatography-mass spectrometry","volume":"9","author":"Kanani","year":"2007","journal-title":"Metab. Eng."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"133","DOI":"10.1007\/978-1-4939-7643-0_9","article-title":"Untargeted GC-MS metabolomics","volume":"1738","author":"Papadimitropoulos","year":"2018","journal-title":"Methods Mol. Biol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"286","DOI":"10.1016\/j.ifacol.2016.12.140","article-title":"Streamlining GC-MS metabolomic analysis using the M-IOLITE software suite","volume":"49","author":"Klapa","year":"2016","journal-title":"IFAC-Pap. Line"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"374","DOI":"10.2144\/03342mt01","article-title":"TM4: A free, open-source system for microarray data management and analysis","volume":"34","author":"Saeed","year":"2003","journal-title":"Biotechniques"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"134","DOI":"10.1016\/S0076-6879(06)11009-5","article-title":"TM4 microarray software suite","volume":"411","author":"Saeed","year":"2006","journal-title":"Methods Enzymol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"254","DOI":"10.1016\/j.cbi.2014.10.007","article-title":"Aldose reductase inhibition alleviates hyperglycemic effects on human retinal pigment epithelial cells","volume":"234","author":"Chang","year":"2015","journal-title":"Chem. Biol. Interact."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"154","DOI":"10.2337\/diab.37.2.154","article-title":"Increased rate of Cori cycle in obese subjects with NIDDM and effect of weight reduction","volume":"37","author":"Zawadzki","year":"1988","journal-title":"Diabetes"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"165","DOI":"10.1093\/ajcn\/nqy287","article-title":"Inflammatory response to dietary linoleic acid depends on FADS1 genotype","volume":"109","author":"Lankinen","year":"2019","journal-title":"Am. J. Clin. Nutr."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"275","DOI":"10.1016\/j.plipres.2009.05.001","article-title":"Lipolysis and lipid mobilization in human adipose tissue","volume":"48","author":"Lafontan","year":"2009","journal-title":"Prog. Lipid Res."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"17092","DOI":"10.1038\/s41598-017-17220-5","article-title":"Plasma metabolomic profile varies with glucocorticoid dose in patients with congenital adrenal hyperplasia","volume":"7","author":"Alwashih","year":"2017","journal-title":"Sci. Rep."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"e62236","DOI":"10.7554\/eLife.62236","article-title":"Identification of human glucocorticoid response markers using integrated multi-omic analysis from a randomized crossover trial","volume":"10","author":"Chantzichristos","year":"2021","journal-title":"Elife"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"90","DOI":"10.3389\/fcell.2018.00090","article-title":"Beyond the Warburg Effect: How Do Cancer Cells Regulate One-Carbon Metabolism?","volume":"6","author":"Rosenzweig","year":"2018","journal-title":"Front. Cell Dev. Biol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1016\/j.cmet.2016.08.009","article-title":"One-Carbon Metabolism in Health and Disease","volume":"25","author":"Ducker","year":"2017","journal-title":"Cell Metab."},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"Copped\u00e8, F. (2020). One-carbon epigenetics and redox biology of neurodegeneration. Free Radic. Biol. Med.","DOI":"10.1016\/j.freeradbiomed.2020.12.002"},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"Burgess, K., Bennett, C., Mosnier, H., Kwatra, N., Bethel, F., and Jadavji, N.M. (2020). The Antioxidant Role of One-Carbon Metabolism on Stroke. Antioxidants, 9.","DOI":"10.3390\/antiox9111141"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"158","DOI":"10.3892\/ijo.2020.5158","article-title":"Serine, glycine and one-carbon metabolism in cancer (Review)","volume":"58","author":"Pan","year":"2021","journal-title":"Int. J. Oncol."},{"key":"ref_38","first-page":"5","article-title":"Primary generalized glucocorticoid resistance and hypersensitivity: The end-organ involvement in the stress response","volume":"5","author":"Charmandari","year":"2012","journal-title":"Sci. Signal."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"145","DOI":"10.1159\/000330759","article-title":"Primary generalized glucocorticoid resistance and hypersensitivity","volume":"76","author":"Charmandari","year":"2011","journal-title":"Horm. Res. Paediatr."},{"key":"ref_40","first-page":"2270","article-title":"The N363S polymorphism of the glucocorticoid receptor: Potential contribution to central obesity in men and lack of association with other risk factors for coronary heart disease and diabetes mellitus","volume":"86","author":"Dobson","year":"2001","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"404","DOI":"10.1161\/01.HYP.0000055342.40301.DC","article-title":"Association of coronary artery disease with glucocorticoid receptor N363S variant","volume":"41","author":"Lin","year":"2003","journal-title":"Hypertension"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"333","DOI":"10.1210\/rp.59.1.333","article-title":"Polymorphisms in the glucocorticoid receptor gene and their associations with metabolic parameters and body composition","volume":"59","author":"Lamberts","year":"2004","journal-title":"Recent Prog. Horm. Res."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"2506","DOI":"10.1210\/en.2017-03254","article-title":"Single Nucleotide Variations of the Human GR Gene Manifested as Pathologic Mutations or Polymorphisms","volume":"159","author":"Kino","year":"2018","journal-title":"Endocrinology"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"179","DOI":"10.1111\/j.1749-6632.2009.05013.x","article-title":"Clinical features associated with glucocorticoid receptor polymorphisms. An overview","volume":"1179","author":"Manenschijn","year":"2009","journal-title":"Ann. N. Y. Acad. Sci."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"455","DOI":"10.1530\/EJE-15-0381","article-title":"BclI glucocorticoid receptor polymorphism in relation to cardiovascular variables: The Hoorn and CODAM studies","volume":"173","author":"Schaper","year":"2015","journal-title":"Eur. J. Endocrinol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"4963","DOI":"10.1210\/jc.2008-0892","article-title":"A novel point mutation in the amino terminal domain of the human glucocorticoid receptor (hGR) gene enhancing hGR-mediated gene expression","volume":"93","author":"Charmandari","year":"2008","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"729","DOI":"10.1210\/jcem-70-3-729","article-title":"A patient with hypocortisolism and Cushing\u2019s syndrome-like manifestations: Cortisol hyperreactive syndrome","volume":"70","author":"Iida","year":"1990","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_48","first-page":"844","article-title":"Glucocorticoid hypersensitivity syndrome\u2014A case report","volume":"61","author":"Krysiak","year":"2012","journal-title":"West Indian Med. J."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"1306","DOI":"10.1111\/eci.12554","article-title":"Transient generalized glucocorticoid hypersensitivity","volume":"45","author":"Nicolaides","year":"2015","journal-title":"Eur. J. Clin. Investig."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"85","DOI":"10.1159\/000486002","article-title":"Metabolic Syndrome in Cushing\u2019s Syndrome Patients","volume":"49","author":"Korbonits","year":"2018","journal-title":"Front. Horm. Res."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"139","DOI":"10.3803\/EnM.2018.33.2.139","article-title":"Recent Updates on the Diagnosis and Management of Cushing\u2019s Syndrome","volume":"33","author":"Nieman","year":"2018","journal-title":"Endocrinol. Metab."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"445","DOI":"10.1016\/j.tem.2005.10.009","article-title":"Genetic polymorphisms and multifactorial diseases: Facts and fallacies revealed by the glucocorticoid receptor gene","volume":"16","author":"Russcher","year":"2005","journal-title":"Trends Endocrinol. Metab."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"892","DOI":"10.1210\/jc.2003-031235","article-title":"Glucocorticoid sensitivity is determined by a specific glucocorticoid receptor haplotype","volume":"89","author":"Stevens","year":"2004","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"3128","DOI":"10.2337\/diabetes.51.10.3128","article-title":"A polymorphism in the glucocorticoid receptor gene, which decreases sensitivity to glucocorticoids in vivo, is associated with low insulin and cholesterol levels","volume":"51","author":"Koper","year":"2002","journal-title":"Diabetes"},{"key":"ref_55","first-page":"2076","article-title":"Five patients with biochemical and\/or clinical generalized glucocorticoid resistance without alterations in the glucocorticoid receptor gene","volume":"85","author":"Huizenga","year":"2000","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"423","DOI":"10.1016\/0361-9230(91)90136-8","article-title":"Glucocorticoids as modulators in the control of feeding","volume":"27","author":"Castonguay","year":"1991","journal-title":"Brain Res. Bull."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"3754","DOI":"10.1210\/en.2004-0305","article-title":"Chronic stress promotes palatable feeding, which reduces signs of stress: Feedforward and feedback effects of chronic stress","volume":"145","author":"Pecoraro","year":"2004","journal-title":"Endocrinology"},{"key":"ref_58","first-page":"R141","article-title":"Glucocorticoids and insulin: Reciprocal signals for energy balance","volume":"268","author":"Strack","year":"1995","journal-title":"Am. J. Physiol."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"1483","DOI":"10.1152\/japplphysiol.01236.2005","article-title":"Effect of voluntary exercise on peripheral tissue glucocorticoid receptor content and the expression and activity of 11beta-hsd1 in the syrian hamster","volume":"100","author":"Coutinho","year":"2006","journal-title":"J. Appl. Physiol."}],"container-title":["Nutrients"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6643\/13\/6\/2120\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T06:19:55Z","timestamp":1760163595000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6643\/13\/6\/2120"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,6,21]]},"references-count":59,"journal-issue":{"issue":"6","published-online":{"date-parts":[[2021,6]]}},"alternative-id":["nu13062120"],"URL":"https:\/\/doi.org\/10.3390\/nu13062120","relation":{},"ISSN":["2072-6643"],"issn-type":[{"type":"electronic","value":"2072-6643"}],"subject":[],"published":{"date-parts":[[2021,6,21]]}}}