{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T05:02:31Z","timestamp":1791435751976,"version":"4.3.3"},"reference-count":139,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2021,3,25]],"date-time":"2021-03-25T00:00:00Z","timestamp":1616630400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001866","name":"Fonds National de la Recherche Luxembourg","doi-asserted-by":"publisher","award":["INTER\/ANR\/16\/11568350 \u2018MADAM\u2019"],"award-info":[{"award-number":["INTER\/ANR\/16\/11568350 \u2018MADAM\u2019"]}],"id":[{"id":"10.13039\/501100001866","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001866","name":"Fonds National de la Recherche Luxembourg","doi-asserted-by":"publisher","award":["FNR-CORE C16\/BM\/11342695 \u2018MetCOEPs\u2019"],"award-info":[{"award-number":["FNR-CORE C16\/BM\/11342695 \u2018MetCOEPs\u2019"]}],"id":[{"id":"10.13039\/501100001866","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001866","name":"Fonds National de la Recherche Luxembourg","doi-asserted-by":"publisher","award":["C12\/BM\/3985792 \u2018EpiPath\u2019"],"award-info":[{"award-number":["C12\/BM\/3985792 \u2018EpiPath\u2019"]}],"id":[{"id":"10.13039\/501100001866","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001866","name":"Fonds National de la Recherche Luxembourg","doi-asserted-by":"publisher","award":["C19\/SC\/13650569, \u201cALAC\u201d"],"award-info":[{"award-number":["C19\/SC\/13650569, \u201cALAC\u201d"]}],"id":[{"id":"10.13039\/501100001866","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000921","name":"European Cooperation in Science and Technology","doi-asserted-by":"publisher","award":["CA18211"],"award-info":[{"award-number":["CA18211"]}],"id":[{"id":"10.13039\/501100000921","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>The physiological response to a psychological stressor broadly impacts energy metabolism. Inversely, changes in energy availability affect the physiological response to the stressor in terms of hypothalamus, pituitary adrenal axis (HPA), and sympathetic nervous system activation. Glucocorticoids, the endpoint of the HPA axis, are critical checkpoints in endocrine control of energy homeostasis and have been linked to metabolic diseases including obesity, insulin resistance, and type 2 diabetes. Glucocorticoids, through the glucocorticoid receptor, activate transcription of genes associated with glucose and lipid regulatory pathways and thereby control both physiological and pathophysiological systemic energy homeostasis. Here, we summarize the current knowledge of glucocorticoid functions in energy metabolism and systemic metabolic dysfunction, particularly focusing on glucose and lipid metabolism. There are elements in the external environment that induce lifelong changes in the HPA axis stress response and glucocorticoid levels, and the most prominent are early life adversity, or exposure to traumatic stress. We hypothesise that when the HPA axis is so disturbed after early life adversity, it will fundamentally alter hepatic gluconeogenesis, inducing hyperglycaemia, and hence crystalise the significant lifelong risk of developing either the metabolic syndrome, or type 2 diabetes. This gives a \u201cJekyll and Hyde\u201d role to gluconeogenesis, providing the necessary energy in situations of acute stress, but driving towards pathophysiological consequences when the HPA axis has been altered.<\/jats:p>","DOI":"10.3390\/ijms22073344","type":"journal-article","created":{"date-parts":[[2021,3,25]],"date-time":"2021-03-25T02:54:03Z","timestamp":1616640843000},"page":"3344","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":44,"title":["The \u2018Jekyll and Hyde\u2019 of Gluconeogenesis: Early Life Adversity, Later Life Stress, and Metabolic Disturbances"],"prefix":"10.3390","volume":"22","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9297-4616","authenticated-orcid":false,"given":"Snehaa V.","family":"Seal","sequence":"first","affiliation":[{"name":"Immune Endocrine and Epigenetics Research Group, Department of Infection and Immunity, Luxembourg Institute of Health (LIH), L-4354 Esch-sur-Alzette, Luxembourg"},{"name":"Faculty of Science, Technology and Medicine, University of Luxembourg, L-4365 Esch-sur-Alzette, Luxembourg"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2760-1071","authenticated-orcid":false,"given":"Jonathan D.","family":"Turner","sequence":"additional","affiliation":[{"name":"Immune Endocrine and Epigenetics Research Group, Department of Infection and Immunity, Luxembourg Institute of Health (LIH), L-4354 Esch-sur-Alzette, Luxembourg"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,3,25]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"290","DOI":"10.1038\/nrn3918","article-title":"Stress and the social brain: Behavioural effects and neurobiological mechanisms","volume":"16","author":"Sandi","year":"2015","journal-title":"Nat. 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