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GDF15 is a cell stress cytokine with a widespread expression and pleiotropic effects, which both seem to be in contrast to the reported highly specialized localization of its receptor. This discrepancy prompts us to re-evaluate the expression pattern of GFRAL in the brain and peripheral tissues of mice. In this detailed immunohistochemical study, we provide evidence for a more widespread distribution of this receptor. Apart from the AP\/NTS region, GFRAL-immunoreactivity was found in the prefrontal cortex, hippocampus, nucleus arcuatus and peripheral tissues including liver, small intestine, fat, kidney and muscle tissues. This widespread receptor expression, not taken into consideration so far, may explain the multiple effects of GDF-15 that are not yet assigned to GFRAL. Furthermore, our results could be relevant for the development of novel pharmacological therapies for physical and mental disorders related to body image and food intake, such as eating disorders, cachexia and obesity.<\/jats:p>","DOI":"10.3390\/nu16050734","type":"journal-article","created":{"date-parts":[[2024,3,4]],"date-time":"2024-03-04T08:03:47Z","timestamp":1709539427000},"page":"734","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":41,"title":["GFRAL Is Widely Distributed in the Brain and Peripheral Tissues of Mice"],"prefix":"10.3390","volume":"16","author":[{"given":"Karoline","family":"Fichtner","sequence":"first","affiliation":[{"name":"Rudolf Boehm Institute of Pharmacology and Toxicology, Faculty of Medicine, University of Leipzig, D-04103 Leipzig, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hermann","family":"Kalwa","sequence":"additional","affiliation":[{"name":"Rudolf Boehm Institute of Pharmacology and Toxicology, Faculty of Medicine, University of Leipzig, D-04103 Leipzig, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miao-Miao","family":"Lin","sequence":"additional","affiliation":[{"name":"Rudolf Boehm Institute of Pharmacology and Toxicology, Faculty of Medicine, University of Leipzig, D-04103 Leipzig, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2984-2960","authenticated-orcid":false,"given":"Yuanyuan","family":"Gong","sequence":"additional","affiliation":[{"name":"Rudolf Boehm Institute of Pharmacology and Toxicology, Faculty of Medicine, University of Leipzig, D-04103 Leipzig, Germany"},{"name":"School of Acupuncture and Tuina, Chengdu University of Traditional Chinese Medicine, Chengdu 610075, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5623-4728","authenticated-orcid":false,"given":"Anne","family":"M\u00fcglitz","sequence":"additional","affiliation":[{"name":"Rudolf Boehm Institute of Pharmacology and Toxicology, Faculty of Medicine, University of Leipzig, D-04103 Leipzig, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Kluge","sequence":"additional","affiliation":[{"name":"Department of Psychiatry and Psychotherapy, University of Leipzig, D-04103 Leipzig, Germany"},{"name":"Department of Psychiatry, Rudolf-Virchow-Klinikum Glauchau, D-08371 Glauchau, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2317-2302","authenticated-orcid":false,"given":"Ute","family":"Kr\u00fcgel","sequence":"additional","affiliation":[{"name":"Rudolf Boehm Institute of Pharmacology and Toxicology, Faculty of Medicine, University of Leipzig, D-04103 Leipzig, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,3,4]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"255","DOI":"10.1038\/nature24042","article-title":"Non-homeostatic body weight regulation through a brainstem-restricted receptor for GDF15","volume":"550","author":"Hsu","year":"2017","journal-title":"Nature"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1150","DOI":"10.1038\/nm.4392","article-title":"GFRAL is the receptor for GDF15 and the ligand promotes weight loss in mice and nonhuman primates","volume":"23","author":"Mullican","year":"2017","journal-title":"Nat. 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