title: Enhanced phase II detoxification contributes to beneficial effects of dietary restriction as revealed by multi-platform metabolomics studies.
abstract: Dietary restriction (DR) has many beneficial effects, but the detailed metabolic mechanism remains largely unresolved. As diet is essentially related to metabolism, we investigated the metabolite profiles of urines from control and DR animals using NMR and LC/MS metabolomic approaches. Multivariate analysis presented distinctive metabolic profiles and marker signals from glucuronide and glycine conjugation pathways in the DR group. Broad profiling of the urine phase II metabolites with neutral loss scanning showed that levels of glucuronide and glycine conjugation metabolites were generally higher in the DR group. The up-regulation of phase II detoxification in the DR group was confirmed by mRNA and protein expression levels of uridinediphospho-glucuronosyltransferase and glycine-N-acyltransferase in actual liver tissues. Histopathology and serum biochemistry showed that DR was correlated with the beneficial effects of low levels of serum alanine transaminase and glycogen granules in liver. In addition, the Nuclear factor (erythroid-derived 2)-like 2 signaling pathway was shown to be up-regulated, providing a mechanistic clue regarding the enhanced phase II detoxification in liver tissue. Taken together, our metabolomic and biochemical studies provide a possible metabolic perspective for understanding the complex mechanism underlying the beneficial effects of DR.
authors.affiliation: College of Pharmacy, Natural Product Research Institute, Seoul National University, Sillim-dong, Gwanak-gu, Seoul, Korea.
authors.forename: He
authors.initials: H
authors.lastname: Wen
authors.forename: Hye-Ji
authors.initials: HJ
authors.lastname: Yang
authors.forename: Yong Jin
authors.initials: YJ
authors.lastname: An
authors.forename: Joon Mee
authors.initials: JM
authors.lastname: Kim
authors.forename: Dae Hyun
authors.initials: DH
authors.lastname: Lee
authors.forename: Xing
authors.initials: X
authors.lastname: Jin
authors.forename: Sung-Woo
authors.initials: SW
authors.lastname: Park
authors.forename: Kyung-Jin
authors.initials: KJ
authors.lastname: Min
authors.forename: Sunghyouk
authors.initials: S
authors.lastname: Park
mesh_terms: D000217:Acyltransferases / Q000235:genetics / Q000378:metabolism; D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D015153:Blotting, Western; D031204:Caloric Restriction; D002851:Chromatography, High Pressure Liquid; D020719:Glucuronides / Q000378:metabolism; D014453:Glucuronosyltransferase / Q000235:genetics / Q000378:metabolism; D005998:Glycine / Q000378:metabolism; D006003:Glycogen / Q000378:metabolism; D008099:Liver / Q000378:metabolism; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D013058:Mass Spectrometry; D050217:Metabolic Detoxication, Phase II / Q000235:genetics / Q000502:physiology*; D055442:Metabolome / Q000235:genetics / Q000502:physiology*; D055432:Metabolomics / Q000379:methods*; D015778:Minor Histocompatibility Antigens; D015999:Multivariate Analysis; D051381:Rats; D017207:Rats, Sprague-Dawley; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015854:Up-Regulation; D000099148:UGT1A1 Enzyme
chemical_list: D000217:Acyltransferases; D000410:Alanine Transaminase; D020719:Glucuronides; D014453:Glucuronosyltransferase; D005998:Glycine; D006003:Glycogen; D015778:Minor Histocompatibility Antigens; C499946:Ugt1a1 protein, rat; D000099148:UGT1A1 Enzyme; C020680:glycine acyltransferase; C583026:glucuronosyltransferase 2B, rat