{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,18]],"date-time":"2026-09-18T13:17:04Z","timestamp":1789737424416,"version":"4.0.1"},"reference-count":70,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2025,4,25]],"date-time":"2025-04-25T00:00:00Z","timestamp":1745539200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Obesity is a multifactorial condition linked to severe health complications, including cardiovascular diseases and endothelial dysfunction. Both obesity and high-fat diets (HFDs) are strongly associated with neuroinflammation, particularly in the hypothalamus. The autonomic nervous system (ANS), which controls involuntary physiological processes, is critical for maintaining cardiovascular health, and its dysfunction is implicated in endothelial disorders. With its homeostatic control centers located in the hypothalamus and brainstem, a crucial question arises: could obesity- and HFD-induced neuroinflammation disrupt central ANS structures, leading to ANS dysfunction and subsequent endothelial disorders? This review examined whether neuroinflammation caused by obesity and HFD contributes to endothelial dysfunction through the dysregulation of the ANS. Our analysis revealed that hypothalamic inflammation linked to obesity and an HFD is associated with sympathetic hyperactivity and endothelial disorders. Identified molecular mechanisms include the influence of inflammatory cytokines, activation of the NF-\u03baB\/IKK-\u03b2 pathway, microglial activation mediated by angiotensin II, circulating mitochondria triggering cGAS activation, and the stimulation of the TLR4 pathway. Our findings suggest that hypothalamic inflammation may play a central role in the interplay between obesity\/an HFD, ANS dysfunction, and endothelial disorders.<\/jats:p>","DOI":"10.3390\/ijms26094047","type":"journal-article","created":{"date-parts":[[2025,4,25]],"date-time":"2025-04-25T04:08:24Z","timestamp":1745554104000},"page":"4047","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":24,"title":["Obesity- and High-Fat-Diet-Induced Neuroinflammation: Implications for Autonomic Nervous System Dysfunction and Endothelial Disorders"],"prefix":"10.3390","volume":"26","author":[{"given":"Galateia","family":"Stathori","sequence":"first","affiliation":[{"name":"Center for the Prevention and Management of Overweight and Obesity, Division of Endocrinology, Metabolism and Diabetes, First Department of Pediatrics, Medical School, National and Kapodistrian University of Athens, \u2018Aghia Sophia\u2019 Children\u2019s Hospital, 11527 Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nikolaos F.","family":"Vlahos","sequence":"additional","affiliation":[{"name":"Second Department of Obstetrics and Gynecology, Medical School, National and Kapodistrian University of Athens, \u2018Aretaieion\u2019 University Hospital, 11528 Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Evangelia","family":"Charmandari","sequence":"additional","affiliation":[{"name":"Center for the Prevention and Management of Overweight and Obesity, Division of Endocrinology, Metabolism and Diabetes, First Department of Pediatrics, Medical School, National and Kapodistrian University of Athens, \u2018Aghia Sophia\u2019 Children\u2019s Hospital, 11527 Athens, Greece"},{"name":"Division of Endocrinology and Metabolism, Center of Clinical, Experimental Surgery and Translational Research, Biomedical Research Foundation of the Academy of Athens, 11527 Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Georgios","family":"Valsamakis","sequence":"additional","affiliation":[{"name":"Second Department of Obstetrics and Gynecology, Medical School, National and Kapodistrian University of Athens, \u2018Aretaieion\u2019 University Hospital, 11528 Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,4,25]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"972","DOI":"10.1016\/S0140-6736(24)01210-8","article-title":"Obesity in adults","volume":"404","author":"Lingvay","year":"2024","journal-title":"Lancet"},{"key":"ref_2","first-page":"e22711","article-title":"Obesity: A Chronic Low-Grade Inflammation and Its Markers","volume":"14","author":"Khanna","year":"2022","journal-title":"Cureus"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"2407","DOI":"10.2337\/db17-0067","article-title":"Hypothalamic Inflammation in Human Obesity Is Mediated by Environmental and Genetic Factors","volume":"66","author":"Kreutzer","year":"2017","journal-title":"Diabetes"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"78","DOI":"10.5688\/aj710478","article-title":"Physiology of the autonomic nervous system","volume":"71","author":"McCorry","year":"2007","journal-title":"Am. 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