{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,27]],"date-time":"2026-02-27T16:52:45Z","timestamp":1772211165666,"version":"3.50.1"},"reference-count":44,"publisher":"Public Library of Science (PLoS)","issue":"11","license":[{"start":{"date-parts":[[2021,11,2]],"date-time":"2021-11-02T00:00:00Z","timestamp":1635811200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100005909","name":"University of California Institute for Mexico and the United States","doi-asserted-by":"publisher","award":["440553"],"award-info":[{"award-number":["440553"]}],"id":[{"id":"10.13039\/100005909","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100006545","name":"National Institute on Minority Health and Health Disparities","doi-asserted-by":"publisher","award":["9T37-MD001480"],"award-info":[{"award-number":["9T37-MD001480"]}],"id":[{"id":"10.13039\/100006545","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"abstract":"<jats:p>\n                    Caloric restriction (CR) is one of the most important behavioral interventions to reduce excessive abdominal adiposity, which is a risk factor for the development of insulin resistance. Previous metabolomics studies have characterized substrate metabolism during healthy conditions; however, the effects of CR and subsequent mass recovery on shifts in substrate metabolism during insulin resistance (IR) have not been widely investigated. To assess the effects of acute CR and the subsequent mass recovery on shifts in substrate metabolism, a cohort of 15-week old Long Evans Tokushima Otsuka (LETO) and Otsuka Long Evans Tokushima Fatty (OLETF) rats were calorie restricted (CR: 50% \u00d7 10 days) with or without partial body mass recovery (PR; 73% x 7 days), along with their respective\n                    <jats:italic>ad libitum<\/jats:italic>\n                    controls. End-of-study plasma samples were analyzed for primary carbon metabolites by gas chromatography (GC) time-of-flight (TOF) mass spectrometry (MS) data acquisition. Data analysis included PCA, Pearson correlation vs previously reported variables (adipose and body masses, and insulin resistance index, IRI), and metabolomics maps (MetaMapp) generated for the most significant group comparisons. All treatments elicited a significant group differentiation in at least one principal component. CR improved TCA cycle in OLETF, and increased lipolysis and proteolysis. These changes were reversed after PR except for gluconeogenesis. Plasma lipid concentrations were inversely correlated to IRI in LETO, but not OLETF. These shifts in substrate metabolism suggest that the CR-induced decreases in adipose may not be sufficient to more permanently alter substrate metabolism to improve IR status during metabolic syndrome.\n                  <\/jats:p>","DOI":"10.1371\/journal.pone.0252360","type":"journal-article","created":{"date-parts":[[2021,11,2]],"date-time":"2021-11-02T13:47:20Z","timestamp":1635860840000},"page":"e0252360","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":0,"title":["Mass recovery following caloric restriction reverses lipolysis and proteolysis, but not gluconeogenesis, in insulin resistant OLETF rats"],"prefix":"10.1371","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2446-8674","authenticated-orcid":true,"given":"Manuel A.","family":"Cornejo","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4798-9111","authenticated-orcid":true,"given":"Jaapna","family":"Dhillon","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Akira","family":"Nishiyama","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Daisuke","family":"Nakano","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rudy M.","family":"Ortiz","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"340","published-online":{"date-parts":[[2021,11,2]]},"reference":[{"issue":"5","key":"pone.0252360.ref001","doi-asserted-by":"crossref","first-page":"937","DOI":"10.1016\/S0735-1097(02)02051-X","article-title":"Relationship between obesity, insulin resistance, and coronary heart disease risk","volume":"40","author":"F Abbasi","year":"2002","journal-title":"J Am Coll Cardiol"},{"issue":"4","key":"pone.0252360.ref002","doi-asserted-by":"crossref","first-page":"757","DOI":"10.1007\/s00125-009-1637-8","article-title":"Insulin resistance is associated with a metabolic profile of altered protein metabolism in Chinese and Asian-Indian men","volume":"53","author":"ES Tai","year":"2010","journal-title":"Diabetologia"},{"issue":"1","key":"pone.0252360.ref003","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1016\/j.cmet.2007.10.013","article-title":"Mitochondrial Overload and Incomplete Fatty Acid Oxidation Contribute to Skeletal Muscle Insulin Resistance","volume":"7","author":"TR Koves","year":"2008","journal-title":"Cell Metab"},{"issue":"3","key":"pone.0252360.ref004","doi-asserted-by":"crossref","first-page":"161","DOI":"10.1002\/ddr.20359","article-title":"Targeting the pentose phosphate pathway in syndrome X-related cardiovascular complications","volume":"71","author":"SA Gupte","year":"2010","journal-title":"Drug Dev Res"},{"key":"pone.0252360.ref005","doi-asserted-by":"crossref","first-page":"958","DOI":"10.1152\/ajpendo.00052.2016","article-title":"Plasma amino acid and metabolite signatures tracking diabetes progression in the UCD-T2DM rat model","volume":"310","author":"BD Piccolo","year":"2016","journal-title":"Am J Physiol\u2014Endocrinol Metab"},{"issue":"3","key":"pone.0252360.ref006","doi-asserted-by":"crossref","first-page":"722","DOI":"10.1172\/JCI108519","article-title":"Composition of weight lost during short term weight reduction. 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