title: Dietary whey protein stimulates mitochondrial activity and decreases oxidative stress in mouse female brain.
abstract: In humans and experimental animals, protein-enriched diets are beneficial for weight management, muscle development, managing early stage insulin resistance and overall health. Previous studies have shown that in mice consuming a high fat diet, whey protein isolate (WPI) reduced hepatosteatosis and insulin resistance due in part to an increase in basal metabolic rate. In the current study, we examined the ability of WPI to increase energy metabolism in mouse brain. Female C57BL/6J mice were fed a normal AIN-93M diet for 12 weeks, with (WPI group) or without (Control group) 100g WPI/L drinking water. In WPI mice compared to controls, the oxidative stress biomarkers malondialdehyde and 4-hydroxyalkenals were 40% lower in brain homogenates, and the production of hydrogen peroxide and superoxide were 25-35% less in brain mitochondria. Brain mitochondria from WPI mice remained coupled, and exhibited higher rates of respiration with proportionately greater levels of cytochromes a+a3 and c+c1. These results suggested that WPI treatment increased the number or improved the function of brain mitochondria. qRT-PCR revealed that the gene encoding a master regulator of mitochondrial activity and biogenesis, Pgc-1alpha (peroxisome proliferator-activated receptor-gamma coactivator-1alpha) was elevated 2.2-fold, as were the PGC-1alpha downstream genes, Tfam (mitochondrial transcription factor A), Gabpa/Nrf-2a (GA-binding protein alpha/nuclear respiratory factor-2a), and Cox-6a1 (cytochrome oxidase-6a1). Each of these genes had twice the levels of transcript in brain tissue from WPI mice, relative to controls. There was no change in the expression of the housekeeping gene B2mg (beta-2 microglobulin). We conclude that dietary whey protein decreases oxidative stress and increases mitochondrial activity in mouse brain. Dietary supplementation with WPI may be a useful clinical intervention to treat conditions associated with oxidative stress or diminished mitochondrial activity in the brain.
authors.affiliation: Department of Environmental Health and Center for Environmental Genetics, University of Cincinnati Medical Center, P.O. Box 670056, Cincinnati, OH 45267, USA. shertzhg@ucmail.uc.edu
authors.forename: Howard G
authors.initials: HG
authors.lastname: Shertzer
authors.forename: Mansi
authors.initials: M
authors.lastname: Krishan
authors.forename: Mary Beth
authors.initials: MB
authors.lastname: Genter
mesh_terms: D000284:Administration, Oral; D000818:Animals; D001921:Brain / Q000187:drug effects / Q000502:physiology*; D004044:Dietary Proteins / Q000378:metabolism*; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D008894:Milk Proteins / Q000008:administration & dosage*; D008928:Mitochondria / Q000187:drug effects / Q000502:physiology*; D018384:Oxidative Stress / Q000187:drug effects / Q000502:physiology*; D017382:Reactive Oxygen Species / Q000378:metabolism*; D000067816:Whey Proteins
chemical_list: D004044:Dietary Proteins; D008894:Milk Proteins; D017382:Reactive Oxygen Species; D000067816:Whey Proteins
keywords: B2MG; Brain; CNS; COX-6A1; ERR; G/M; GA-binding protein alpha (mouse)/nuclear respiratory factor-2a (human); GABPA/NRF-2A; Gene expression; MFN2; Mitochondria; Mouse; Oxidative stress; PGC-1a; PPAR; ROS; Succ; TFAM; WPI; Whey protein; beta-2 microglobulin; central nervous system; cytochrome oxidase-6a1; estrogen-related receptor; glutamate+malate; mitochondrial transcription factor A; mitofusin-2; peroxisome proliferator-activated receptor; peroxisome proliferator-activated receptor-gamma coactivator-1alpha; qRT-PCR; quantitative real-time polymerase chain reaction; reactive oxygen species; succinate; whey protein isolate