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Though the cerebellum is more commonly associated with motor control, it has strong links with the hypothalamus and is thought to be associated with nutritional regulation and adiposity. Using a global mass spectrometry-based metabolomics approach, we identified 756 metabolites that were significantly differentially expressed in the cerebellar region of the brain of C57BL\/6J mice, fed graded levels of CR (10, 20, 30, and 40 CR) compared to mice fed ad libitum for 12 hours a day. Pathway enrichment indicated changes in the pathways of adenosine and guanine (which are precursors of DNA production), aromatic amino acids (tyrosine, phenylalanine, and tryptophan) and the sulfur-containing amino acid methionine. We also saw increases in the tricarboxylic acid cycle (TCA) cycle, electron donor, and dopamine and histamine pathways. In particular, changes in l-histidine and homocarnosine correlated positively with the level of CR and food anticipatory activity and negatively with insulin and body temperature. Several metabolic and pathway changes acted against changes seen in age-associated neurodegenerative disorders, including increases in the TCA cycle and reduced l-proline. Carnitine metabolites contributed to discrimination between CR groups, which corroborates previous work in the liver and plasma. These results indicate the conservation of certain aspects of metabolism across tissues with CR. Moreover, this is the first study to indicate CR alters the cerebellar metabolome, and does so in a graded fashion, after only a short period of restriction.<\/jats:p>","DOI":"10.1093\/gerona\/glaa261","type":"journal-article","created":{"date-parts":[[2020,10,14]],"date-time":"2020-10-14T18:59:18Z","timestamp":1602701958000},"page":"601-610","source":"Crossref","is-referenced-by-count":8,"title":["The Effects of Graded Levels of Calorie Restriction: XVI. Metabolomic Changes in the Cerebellum Indicate Activation of Hypothalamocerebellar Connections Driven by Hunger Responses"],"prefix":"10.1093","volume":"76","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2293-9364","authenticated-orcid":false,"given":"Cara L","family":"Green","sequence":"first","affiliation":[{"name":"Institute of Biological and Environmental Sciences, University of Aberdeen, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sharon E","family":"Mitchell","sequence":"additional","affiliation":[{"name":"Institute of Biological and Environmental Sciences, University of Aberdeen, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9041-4607","authenticated-orcid":false,"given":"Davina","family":"Derous","sequence":"additional","affiliation":[{"name":"Institute of Biological and Environmental Sciences, University of Aberdeen, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Libia A","family":"Garc\u00eda-Flores","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Molecular Developmental Biology, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yingchun","family":"Wang","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Molecular Developmental Biology, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luonan","family":"Chen","sequence":"additional","affiliation":[{"name":"Key Laboratory of Systems Biology, Innovation Center for Cell Signaling Network, Institute of Biochemistry and Cell Biology, Shanghai Institute of Biological Sciences, Chinese Academy of Sciences, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing-Dong J","family":"Han","sequence":"additional","affiliation":[{"name":"Chinese Academy of Sciences Key Laboratory of Computational Biology, Chinese Academy of Sciences-Max Planck Partner Institute for Computational Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7088-4495","authenticated-orcid":false,"given":"Daniel E L","family":"Promislow","sequence":"additional","affiliation":[{"name":"Department of Pathology and Department of Biology, University of Washington at Seattle"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Lusseau","sequence":"additional","affiliation":[{"name":"Institute of Biological and Environmental Sciences, University of Aberdeen, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alex","family":"Douglas","sequence":"additional","affiliation":[{"name":"Institute of Biological and Environmental Sciences, University of Aberdeen, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John R","family":"Speakman","sequence":"additional","affiliation":[{"name":"Institute of Biological and Environmental Sciences, University of Aberdeen, UK"},{"name":"State Key Laboratory of Molecular Developmental Biology, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2020,10,14]]},"reference":[{"key":"2021033117163901800_CIT0001","doi-asserted-by":"crossref","first-page":"197","DOI":"10.1007\/s12311-014-0627-7","article-title":"Consensus paper: the role of the cerebellum in perceptual processes","volume":"14","author":"Baumann","year":"2015","journal-title":"Cerebellum"},{"key":"2021033117163901800_CIT0002","doi-asserted-by":"crossref","first-page":"1063","DOI":"10.1016\/0031-9384(93)90325-A","article-title":"An unexpected role of the cerebellum: involvement in nutritional organization","volume":"54","author":"Mahler","year":"1993","journal-title":"Physiol Behav"},{"key":"2021033117163901800_CIT0003","article-title":"The effects of graded levels of calorie restriction: V. 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