title: A high-fat diet differentially regulates glutathione phenotypes in the obesity-prone mouse strains DBA/2J, C57BL/6J, and AKR/J.
abstract: The ubiquitous tripeptide glutathione (GSH) is a critical component of the endogenous antioxidant defense system. Tissue GSH concentrations and redox status (GSH/GSSG) are genetically controlled, but it is unclear whether interactions between genetic background and diet affect GSH homeostasis. The current study tested the hypothesis that a high-fat diet regulates GSH homeostasis in a manner dependent on genetic background. At 4 months of age, female mice representing 3 obesity-prone inbred strains-C57BL/6J (B6), DBA/2J (D2), and AKR/J (AKR)-were randomly assigned to consume a control (10% energy from fat) or high-fat (62% energy from fat) diet for 10 weeks (n=5/diet per strain). Tissue GSH levels, GSSG levels, and GSH/GSSG were quantified, and hepatic expression of GSH-related enzymes was evaluated by quantitative reverse transcription polymerase chain reaction. The high-fat diet caused a decrease in hepatic GSH/GSSG in D2 mice. In contrast, B6 mice exhibited a decrease in GSSG levels in the liver and kidney, as well as a resultant increase in renal GSH/GSSG. AKR mice also exhibited increased renal GSH/GSSG on a high-fat diet. Finally, the high-fat diet induced a unique gene expression response in D2 mice compared with B6 and AKR. The D2 response was characterized by up-regulation of glutamate-cysteine ligase modifier subunit and down-regulation of glutathione reductase, whereas the B6 and AKR responses were characterized by up-regulation of glutathione peroxidase 1. Two-way analysis of variance analyses confirmed several diet-strain interactions within the GSH system, and linear regression models highlighted relationships between body mass and GSH outcomes as well. Overall, our data indicate that dietary fat regulates the GSH system in a strain-dependent manner.
authors.affiliation: Department of Foods and Nutrition, University of Georgia, 305 Sanford Dr, Athens, GA 30602, USA. Electronic address: kmn@uga.edu.
authors.forename: Katie M
authors.initials: KM
authors.lastname: Norris
authors.affiliation: Department of Foods and Nutrition, University of Georgia, 305 Sanford Dr, Athens, GA 30602, USA. Electronic address: whitokie@uga.edu.
authors.forename: Whitney
authors.initials: W
authors.lastname: Okie
authors.affiliation: Department of Poultry Science, University of Georgia, 110 Cedar St, Athens, GA 30602, USA. Electronic address: wkkim@uga.edu.
authors.forename: Woo Kyun
authors.initials: WK
authors.lastname: Kim
authors.affiliation: Department of Poultry Science, University of Georgia, 110 Cedar St, Athens, GA 30602, USA. Electronic address: adhikarr@uga.edu.
authors.forename: Roshan
authors.initials: R
authors.lastname: Adhikari
authors.affiliation: Department of Foods and Nutrition, University of Georgia, 305 Sanford Dr, Athens, GA 30602, USA. Electronic address: sarahyoo92@gmail.com.
authors.forename: Sarah
authors.initials: S
authors.lastname: Yoo
authors.affiliation: Department of Foods and Nutrition, University of Georgia, 305 Sanford Dr, Athens, GA 30602, USA. Electronic address: skk94@uga.edu.
authors.forename: Stephanie
authors.initials: S
authors.lastname: King
authors.affiliation: Department of Foods and Nutrition, University of Georgia, 305 Sanford Dr, Athens, GA 30602, USA. Electronic address: rpazdro@uga.edu.
authors.forename: Robert
authors.initials: R
authors.lastname: Pazdro
mesh_terms: D000818:Animals; D001835:Body Weight; D059305:Diet, High-Fat / Q000009:adverse effects*; D004041:Dietary Fats / Q000008:administration & dosage / Q000009:adverse effects*; D015536:Down-Regulation; D005260:Female; D059647:Gene-Environment Interaction; D005721:Glutamate-Cysteine Ligase / Q000378:metabolism; D005978:Glutathione / Q000378:metabolism*; D019803:Glutathione Disulfide / Q000378:metabolism; D005979:Glutathione Peroxidase / Q000378:metabolism; D005980:Glutathione Reductase / Q000378:metabolism; D006706:Homeostasis; D007668:Kidney / Q000378:metabolism; D008099:Liver / Q000378:metabolism; D008806:Mice, Inbred AKR; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D008820:Mice, Obese; D009765:Obesity / Q000209:etiology / Q000235:genetics* / Q000378:metabolism; D010641:Phenotype; D011897:Random Allocation; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015854:Up-Regulation; D000094765:Glutathione Peroxidase GPX1
chemical_list: D004041:Dietary Fats; D005979:Glutathione Peroxidase; D005980:Glutathione Reductase; C560749:GCLM protein, mouse; D005721:Glutamate-Cysteine Ligase; D005978:Glutathione; D019803:Glutathione Disulfide; D000094765:Glutathione Peroxidase GPX1; C000722068:Gpx1 protein, mouse
keywords: Antioxidant; GSH/GSSG; Genetics; Glutathione; High-fat diet; Obesity