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Still, various knowledge gaps persist, including on underlying pathophysiological mechanisms. The aim of the current review is to provide the latest insights on the connection between stress and obesity. We discuss three biological stress systems\u2014the autonomic nervous system, the hypothalamus\u2013pituitary\u2013adrenal (HPA) axis and the immune system\u2014and their link with obesity, with a particular focus on the HPA axis. The role of cortisol and its regulatory variations (including glucocorticoid rhythmicity and altered sensitivity) in adipose tissue biology and obesity development is discussed. Moreover, we highlight the physiological, affective, cognitive and behavioural dimensions of the stress response offering a deeper understanding of how stress contributes to obesity development and vice versa. Finally, stress as a treatment target for obesity is discussed. We conclude that the link between stress and obesity is complex and multifaceted, influenced by physiological, affective, cognitive and behavioural stress response mechanisms, which especially when chronically present, play a key role in the development of obesity and associated cardiometabolic diseases. This necessitates integrated approaches tailored to individual needs, including lifestyle modifications, behavioural interventions, psychosocial support and possible additional pharmacological interventions.<\/jats:p>","DOI":"10.1111\/cob.12725","type":"journal-article","created":{"date-parts":[[2024,12,3]],"date-time":"2024-12-03T05:15:10Z","timestamp":1733202910000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":72,"title":["Glucocorticoids and <scp>HPA<\/scp> axis regulation in the stress\u2013obesity connection: A comprehensive overview of biological, physiological and behavioural dimensions"],"prefix":"10.1111","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5666-4824","authenticated-orcid":false,"given":"Robin","family":"Lengton","sequence":"first","affiliation":[{"name":"Department of Internal Medicine, Division of Endocrinology, Erasmus MC University Medical Center Rotterdam  Rotterdam The Netherlands"},{"name":"Obesity Center CGG, Erasmus MC University Medical Center Rotterdam  Rotterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-3458-162X","authenticated-orcid":false,"given":"Myrte","family":"Schoenmakers","sequence":"additional","affiliation":[{"name":"Department of Biological Psychology Vrije Universiteit  Amsterdam The Netherlands"},{"name":"Amsterdam Public Health research institute Amsterdam UMC  Amsterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7779-9672","authenticated-orcid":false,"given":"Brenda W. 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