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Mendelian randomization analyses tested whether six body fat measures affect brain volume, intelligence, cognitive performance, and 19 neuropsychiatric diseases, using cross-trait meta-analysis and colocalization. Higher fat composition related to smaller grey matter volume, lower intelligence and cognitive performance, and altered disease risks, while selected brain diseases influenced body fat. Results support a bidirectional fat-brain axis and emphasize disease-specific weight management.",{"@graph":69,"@context":122},[70,84,105],{"@type":71,"itemListElement":72},"BreadcrumbList",[73,77,79,82],{"item":74,"name":75,"@type":76,"position":8},"https://docshare.wps.com","Home","ListItem",{"item":78,"name":9,"@type":76,"position":14},"https://docshare.wps.com/document/",{"item":80,"name":35,"@type":76,"position":81},"https://docshare.wps.com/document/healthcare/",3,{"item":83,"name":65,"@type":76,"position":19},"https://docshare.wps.com/document/fat-brain-axis-indicated-by-mutual-impacts-between-body-fat-and-brain-phenotypes/406974/",{"url":83,"name":65,"@type":85,"image":86,"author":91,"headline":65,"publisher":94,"fileFormat":97,"inLanguage":63,"description":67,"dateModified":98,"datePublished":99,"encodingFormat":97,"isAccessibleForFree":100,"interactionStatistic":101},"DigitalDocument",{"url":87,"@type":88,"width":89,"height":90},"https://docshare.wps.com/thumbnails/fat-brain-axis-indicated-by-mutual-impacts-between-body-fat-and-brain-phenotypes/406974.png","ImageObject",300,407,{"name":92,"@type":93},"nayy☆","Person",{"url":74,"name":95,"@type":96},"DocShare","Organization","application/pdf","2026-10-31","2026-09-28",true,{"@type":102,"interactionType":103,"userInteractionCount":44},"InteractionCounter",{"@type":104},"ViewAction",{"@type":106,"mainEntity":107},"FAQPage",[108,114,118],{"name":109,"@type":110,"acceptedAnswer":111},"What relationship did the study examine between body fat and the brain?","Question",{"text":112,"@type":113},"The study investigated a bidirectional fat-brain axis, assessing whether body fat composition causally affects brain phenotypes and neuropsychiatric disease risks, and whether certain brain diseases causally affect body fat.","Answer",{"name":115,"@type":110,"acceptedAnswer":116},"How were causal effects tested in this research?",{"text":117,"@type":113},"Causality was evaluated using Mendelian randomization (MR) analyses, supported by cross-trait meta-analysis and colocalization for specific trait pairs, including BMI with Alzheimer’s disease and Parkinson’s disease.",{"name":119,"@type":110,"acceptedAnswer":120},"What were the main findings about body fat composition and brain outcomes?",{"text":121,"@type":113},"Higher body fat composition was associated with smaller grey matter volume, reduced intelligence and cognitive performance, and increased risks of 10 neuropsychiatric diseases while decreasing risks of others.","https://schema.org",{"og:url":83,"og:type":124,"og:title":65,"og:site_name":95,"og:description":67},"article",{"robots":126,"canonical":83},"index,follow",{"doc_id":128,"site_id":62},406974,1791124001,{"code":4,"msg":5,"data":131},{"doc_id":128,"user_id":132,"nickname":92,"user_avatar":133,"doc_module":4,"category_id":34,"category_name":35,"doc_title":65,"doc_description":67,"doc_content":134,"file_id":135,"file_url":136,"file_type":137,"file_size":138,"view_count":44,"is_deleted":4,"is_public":8,"is_downloadable":8,"audit_status":8,"page_count":139,"language":140,"language_code":63,"site_id":62,"html_lang":63,"table_of_contents":141,"faqs":142,"seo_title":143,"seo_description":67,"update_tm":144,"read_time":145,"preview_page_count":4},962090893153,"https://ap-avatar.wpscdn.com/davatar_9964176cb1d06d4a9deccf72a44ae3dc","Baranova etal. Journal of Translational Medicine (2025) 23:1436  \n[https://doi.org/10.1186/s12967-025-07453-8](https://doi.org/10.1186/s12967-025-07453-8)  \nJournal of Translational Medicine  \nRESEARCH Open Access  \nFat-brain axis indicated by mutual impacts between body fat and brain phenotypes  \nAncha Baranova 1,2†, Li Fu3†, Qian Zhao3†, Dongming Liu4†, Hongbao Cao 1, Vikas Chandhoke 1 and Fuquan Zhang3,5*  \nAbstract  \nBackground Adipose tissue and the central nervous system regulate each other, but the interactions between body fat composition and brain health remain unclear.  \nMethods To investigate this, we conducted Mendelian randomization (MR) analyses to explore the causality between body fat composition, brain volume, intelligence, cognitive performance (CP), and 19 neuropsychiatric diseases using six body fat measures. We performed cross-trait meta-analysis and colocalization analysis for body mass index (BMI) with Alzheimer’s disease (AD) and Parkinson’s disease (PD) .  \nResults Our findings show that higher body fat composition is associated with smaller grey matter volume, reduced intelligence and CP, increased risks of 10 neuropsychiatric diseases, and decreased risks of others. Additionally, certain brain diseases exert causal effects on body fat. We identified a novel AMDP1-containing genomic locus shared between BMI and PD. Adenosine signaling was highlighted as a cross-talking pathway with opposing effects on PD and BMI-related phenotypes.  \nConclusions These results highlight the bidirectional fat-brain axis and suggest the need for disease-specific weight management strategies.  \nTrial registration Not applicable.  \nKeywords Mendelian randomization, Mental disorder, BMI, Cognition, Body fat  \n†Ancha Baranova, Li Fu, Qian Zhao and Dongming Liu share First authorship.  \n*Correspondence: Fuquan Zhang [zfqeee@126.com](zfqeee@126.com)  \n1School of Systems Biology, George Mason University, Fairfax, VA 22030, USA  \n2Research Centre for Medical Genetics, Moscow 115478, Russia 3Department of Psychiatry, The Affiliated Brain Hospital of Nanjing Medical University, 264 Guangzhou Road, Nanjing 210029, China 4Department of Radiology, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, Jiangsu 210008, China  \n5Institute of Neuropsychiatry, The Affiliated Brain Hospital of Nanjing Medical University, Nanjing 210029, China  \nBackground  \nAn alarming increase in obesity rates has been reported in both children, adolescents, and adults worldwide [1, 2]. Accordingly, obesity has become recognized asa major global health challenge [2, 3]. Obesity-related measures include body mass index (BMI), body fat percentage (BFP), body fat mass (BFM), hip circumference (HC), waist circumference (WC), and waist-to-hip ratio (WHR) [4]. Abdominal obesity index is significantly related to disease risk, but the BMI is deemed the most straightforward measure of obesity [5, 6]. Elevated BMI stands as a primary contributor to the overall health burden and serves as a forecaster of disability-adjusted life-years (DALYs) [7, 8]. On the other hand, for the mortality due to some common diseases, including diabetes,  \n© The Author(s) 2025. Open Access This article is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License, which permits any non-commercial use, sharing, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if you modified the licensed material. You do not have permission under this licence to share adapted material derived from this article or parts of it. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your in","cbCaifpHD8c6G7CD","https://ap.wps.com/l/cbCaifpHD8c6G7CD","pdf",2059228,13,"English","# Abstract\n## Background\n## Methods\n## Results\n## Conclusions\n## Keywords\n## Background\n## Obesity and related health burden\n## Mental and neurological disease burden\n## Pathophysiological rationale (adipokines and neuropsychiatric links)","[{\"question\":\"What relationship did the study examine between body fat and the brain?\",\"answer\":\"The study investigated a bidirectional fat-brain axis, assessing whether body fat composition causally affects brain phenotypes and neuropsychiatric disease risks, and whether certain brain diseases causally affect body fat.\"},{\"question\":\"How were causal effects tested in this research?\",\"answer\":\"Causality was evaluated using Mendelian randomization (MR) analyses, supported by cross-trait meta-analysis and colocalization for specific trait pairs, including BMI with Alzheimer’s disease and Parkinson’s disease.\"},{\"question\":\"What were the main findings about body fat composition and brain outcomes?\",\"answer\":\"Higher body fat composition was associated with smaller grey matter volume, reduced intelligence and cognitive performance, and increased risks of 10 neuropsychiatric diseases while decreasing risks of others.\"}]","Fat-brain axis indicated by mutual impacts between body fat and brain phenotypes | PDF",1790569253,33]