{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,13]],"date-time":"2026-03-13T07:33:01Z","timestamp":1773387181252,"version":"3.50.1"},"reference-count":95,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2021,5,21]],"date-time":"2021-05-21T00:00:00Z","timestamp":1621555200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["1R01AG059088"],"award-info":[{"award-number":["1R01AG059088"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>The triad of obesity, metabolic syndrome (MetS), Type 2 diabetes mellitus (T2DM) and advancing age are currently global societal problems that are expected to grow over the coming decades. This triad is associated with multiple end-organ complications of diabetic vasculopathy (maco-microvessel disease), neuropathy, retinopathy, nephropathy, cardiomyopathy, cognopathy encephalopathy and\/or late-onset Alzheimer\u2019s disease. Further, obesity, MetS, T2DM and their complications are associated with economical and individual family burdens. This review with original data focuses on the white adipose tissue-derived adipokine\/hormone leptin and how its deficient signaling is associated with brain remodeling in hyperphagic, obese, or hyperglycemic female mice. Specifically, the ultrastructural remodeling of the capillary neurovascular unit, brain endothelial cells (BECs) and their endothelial glycocalyx (ecGCx), the blood-brain barrier (BBB), the ventricular ependymal cells, choroid plexus, blood-cerebrospinal fluid barrier (BCSFB), and tanycytes are examined in female mice with impaired leptin signaling from either dysfunction of the leptin receptor (DIO and db\/db models) or the novel leptin deficiency (BTBR ob\/ob model).<\/jats:p>","DOI":"10.3390\/ijms22115427","type":"journal-article","created":{"date-parts":[[2021,5,21]],"date-time":"2021-05-21T13:15:15Z","timestamp":1621602915000},"page":"5427","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":40,"title":["Deficient Leptin Cellular Signaling Plays a Key Role in Brain Ultrastructural Remodeling in Obesity and Type 2 Diabetes Mellitus"],"prefix":"10.3390","volume":"22","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5178-4245","authenticated-orcid":false,"given":"Melvin R.","family":"Hayden","sequence":"first","affiliation":[{"name":"Departments of Internal Medicine, Endocrinology Diabetes and Metabolism, Diabetes and Cardiovascular Disease Center, University of Missouri-Columbia School of Medicine, One Hospital Drive, Columbia, MO 65212, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"William A.","family":"Banks","sequence":"additional","affiliation":[{"name":"Geriatrics Research, Education and Clinical Center, Veterans Affairs Puget Sound Health Care System, 1660 S. Columbian Way, 810C\/Bldg 1, Seattle, WA 98108, USA"},{"name":"Department of Medicine, Division of Gerontology and Geriatric Medicine, University of Washington, Seattle, WA 98108, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2021,5,21]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"S15","DOI":"10.1016\/S0002-8223(98)00704-4","article-title":"Obesity as a chronic disease: Modern medical and lifestyle management","volume":"98","author":"Rippe","year":"1998","journal-title":"J. Am. Diet. Assoc."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"R387","DOI":"10.1152\/ajpregu.00235.2016","article-title":"Cellular mechanisms underlying obesity-induced arterial stiffness","volume":"314","author":"Aroor","year":"2018","journal-title":"Am. J. Physiol. Regul. Integr. Comp. Physiol."},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Hayden, M.R. (2019). 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