Mass recovery following caloric restriction reverses lipolysis and proteolysis, but not gluconeogenesis, in insulin resistant OLETF rats

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 effe...

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Autores principales: Manuel A. Cornejo, Jaapna Dhillon, Akira Nishiyama, Daisuke Nakano, Rudy M. Ortiz
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Publicado: Public Library of Science (PLoS) 2021
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spelling oai:doaj.org-article:a2a7470e4a93457a9612256838478c692021-11-11T06:44:21ZMass recovery following caloric restriction reverses lipolysis and proteolysis, but not gluconeogenesis, in insulin resistant OLETF rats1932-6203https://doaj.org/article/a2a7470e4a93457a9612256838478c692021-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC8562784/?tool=EBIhttps://doaj.org/toc/1932-6203Caloric 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% × 10 days) with or without partial body mass recovery (PR; 73% x 7 days), along with their respective ad libitum 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.Manuel A. CornejoJaapna DhillonAkira NishiyamaDaisuke NakanoRudy M. OrtizPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 16, Iss 11 (2021)
institution DOAJ
collection DOAJ
language EN
topic Medicine
R
Science
Q
spellingShingle Medicine
R
Science
Q
Manuel A. Cornejo
Jaapna Dhillon
Akira Nishiyama
Daisuke Nakano
Rudy M. Ortiz
Mass recovery following caloric restriction reverses lipolysis and proteolysis, but not gluconeogenesis, in insulin resistant OLETF rats
description 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% × 10 days) with or without partial body mass recovery (PR; 73% x 7 days), along with their respective ad libitum 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.
format article
author Manuel A. Cornejo
Jaapna Dhillon
Akira Nishiyama
Daisuke Nakano
Rudy M. Ortiz
author_facet Manuel A. Cornejo
Jaapna Dhillon
Akira Nishiyama
Daisuke Nakano
Rudy M. Ortiz
author_sort Manuel A. Cornejo
title Mass recovery following caloric restriction reverses lipolysis and proteolysis, but not gluconeogenesis, in insulin resistant OLETF rats
title_short Mass recovery following caloric restriction reverses lipolysis and proteolysis, but not gluconeogenesis, in insulin resistant OLETF rats
title_full Mass recovery following caloric restriction reverses lipolysis and proteolysis, but not gluconeogenesis, in insulin resistant OLETF rats
title_fullStr Mass recovery following caloric restriction reverses lipolysis and proteolysis, but not gluconeogenesis, in insulin resistant OLETF rats
title_full_unstemmed Mass recovery following caloric restriction reverses lipolysis and proteolysis, but not gluconeogenesis, in insulin resistant OLETF rats
title_sort mass recovery following caloric restriction reverses lipolysis and proteolysis, but not gluconeogenesis, in insulin resistant oletf rats
publisher Public Library of Science (PLoS)
publishDate 2021
url https://doaj.org/article/a2a7470e4a93457a9612256838478c69
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AT jaapnadhillon massrecoveryfollowingcaloricrestrictionreverseslipolysisandproteolysisbutnotgluconeogenesisininsulinresistantoletfrats
AT akiranishiyama massrecoveryfollowingcaloricrestrictionreverseslipolysisandproteolysisbutnotgluconeogenesisininsulinresistantoletfrats
AT daisukenakano massrecoveryfollowingcaloricrestrictionreverseslipolysisandproteolysisbutnotgluconeogenesisininsulinresistantoletfrats
AT rudymortiz massrecoveryfollowingcaloricrestrictionreverseslipolysisandproteolysisbutnotgluconeogenesisininsulinresistantoletfrats
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