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) 100 g 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.

Effects of protein type and composition on postprandial markers of skeletal muscle anabolism, adipose tissue lipolysis, and hypothalamic gene expression

“…To this end, Canto et al [ 47 ] have demonstrated that AMPK activation increases the expression of these two genes, and this would support the hypothesis that whey protein, in particular WPH, can stimulate oxidative metabolism and mitochondrial biogenesis with long-term supplementation. This hypothesis is not unfounded given recent evidence that prolonged whey protein feeding has been shown to increase mitochondrial content and respiration in the brain [ 48 ] and liver [ 49 ]. Therefore, more mechanistic studies should examine if WPH administration increases the post-feeding expression of mitochondrial-related genes via AMPK activation and/or other mechanisms.…”

Effects of the use of assisted reproduction and high-caloric diet consumption on body weight and cardiovascular health of juvenile mouse offspring

“…B2m has been previously shown to be stable in high-fat diet induced oxidative stress in adipose tissue (Bailey-Downs et al . 2013), and in response to oxidative stress in the brain (Shertzer et al . 2013) and lung (Shimada et al .…”

Milk Consumption and the Risk for Incident Major Depressive Disorder

“…Milk consumption increases circulating insulin-like growth factor-1 and there is a positive association between this factor and depression [4]. Moreover, milk proteins such as lactoferrin impact neuronal differentiation [5], while milk whey protein alters brain mitochondrial activity and oxidative stress markers [6]. As these pathways are implicated in depression, we aimed to examine the relationship between milk intake and the risk for de novo MDD.…”