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Whether this translates to humans is however largely unknown. Using a novel multimodal approach with manual segmentation, we here show that a higher\u00a0body mass index (BMI) selectively predicted higher proton diffusivity within the hypothalamus, indicative of compromised microstructure in the underlying tissue, in a well-characterized population-based cohort (n<jats:sub>1<\/jats:sub>\u2009=\u2009338, 48% females, age 21\u201378 years, BMI 18\u201343\u2009kg\/m\u00b2). Results were independent from confounders and confirmed in another independent sample (n<jats:sub>2<\/jats:sub>\u2009=\u2009236). In addition, while hypothalamic volume was not associated with obesity, we identified a sexual dimorphism and larger hypothalamic volumes in the left compared to the right hemisphere. Using two large samples of the general population, we showed that a higher BMI specifically relates to altered microstructure in the hypothalamus, independent from confounders such as age, sex and obesity-associated co-morbidities. This points to persisting microstructural changes in a key regulatory area of energy homeostasis occurring with excessive weight. Our findings may help to better understand the pathomechanisms of obesity and other eating-related disorders.<\/jats:p>","DOI":"10.1038\/s41598-019-53578-4","type":"journal-article","created":{"date-parts":[[2019,11,22]],"date-time":"2019-11-22T11:02:26Z","timestamp":1574420546000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":66,"title":["Higher body mass index is linked to altered hypothalamic microstructure"],"prefix":"10.1038","volume":"9","author":[{"given":"K.","family":"Thomas","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"F.","family":"Beyer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"G.","family":"Lewe","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"R.","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S.","family":"Schindler","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"P.","family":"Sch\u00f6nknecht","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M.","family":"Stumvoll","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A.","family":"Villringer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A. 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