{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,26]],"date-time":"2026-10-26T22:21:59Z","timestamp":1793053319493,"version":"4.5.0"},"reference-count":85,"publisher":"Oxford University Press (OUP)","issue":"3","license":[{"start":{"date-parts":[[2023,3,2]],"date-time":"2023-03-02T00:00:00Z","timestamp":1677715200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"DOI":"10.13039\/501100003042","name":"Else Kr\u00f6ner-Fresenius-Stiftung","doi-asserted-by":"crossref","award":["2018_Kolleg.01"],"award-info":[{"award-number":["2018_Kolleg.01"]}],"id":[{"id":"10.13039\/501100003042","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2023,3,2]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Obesity and its comorbidities are long-standing, challenging global health problems. Lack of exercise, overnutrition, and especially the consumption of fat-rich foods are some of the most important factors leading to an increase in prevalence in modern society. The pathophysiology of obesity as a metabolic inflammatory disease has moved into focus since new therapeutic approaches are required. The hypothalamus, a brain area responsible for energy homeostasis, has recently received special attention in this regard. Hypothalamic inflammation was identified to be associated with diet-induced obesity and new evidence suggests that it may be, beyond that, a pathological mechanism of the disease. This inflammation impairs the local signaling of insulin and leptin leading to dysfunction of the regulation of energy balance and thus, weight gain. After a high-fat diet consumption, activation of inflammatory mediators such as the nuclear factor \u03baB or c-Jun N-terminal kinase pathway can be observed, accompanied by elevated secretion of pro-inflammatory interleukins and cytokines. Brain resident glia cells, especially microglia and astrocytes, initiate this release in response to the flux of fatty acids. The gliosis occurs rapidly before the actual weight gain. Dysregulated hypothalamic circuits change the interaction between neuronal and non-neuronal cells, contributing to the establishment of inflammatory processes. Several studies have reported reactive gliosis in obese humans. Although there is evidence for a causative role of hypothalamic inflammation in the obesity development, data on underlying molecular pathways in humans are limited. This review discusses the current state of knowledge on the relationship between hypothalamic inflammation and obesity in humans.<\/jats:p>","DOI":"10.1093\/ejendo\/lvad030","type":"journal-article","created":{"date-parts":[[2023,3,7]],"date-time":"2023-03-07T23:58:05Z","timestamp":1678233485000},"page":"R37-R45","source":"Crossref","is-referenced-by-count":42,"title":["Is human obesity an inflammatory disease of the hypothalamus?"],"prefix":"10.1093","volume":"188","author":[{"given":"Lena","family":"Sonnefeld","sequence":"first","affiliation":[{"name":"Institute of Diabetes and Clinical Metabolic Research, University Medical Centre Schleswig-Holstein , Kiel 24105 , Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nathalie","family":"Rohmann","sequence":"additional","affiliation":[{"name":"Institute of Diabetes and Clinical Metabolic Research, University Medical Centre Schleswig-Holstein , Kiel 24105 , Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Corinna","family":"Geisler","sequence":"additional","affiliation":[{"name":"Institute of Diabetes and Clinical Metabolic Research, University Medical Centre Schleswig-Holstein , Kiel 24105 , Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3763-4368","authenticated-orcid":false,"given":"Matthias","family":"Laudes","sequence":"additional","affiliation":[{"name":"Institute of Diabetes and Clinical Metabolic Research, University Medical Centre Schleswig-Holstein , Kiel 24105 , Germany"},{"name":"Division of Endocrinology, Diabetes and Clinical Nutrition, Department of Medicine 1, University Medical Centre Schleswig-Holstein , Kiel 24105 , Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2023,3,8]]},"reference":[{"key":"2023032510162565900_","volume-title":"WHO European Regional Obesity Report 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