Every-Other-Day Feeding Decreases Glycolytic and Mitochondrial Energy-Producing Potentials in the Brain and Liver of Young Mice

Abstract

Intermittent fasting is used to reduce body mass in obese adult humans and animals. However, information on the impact of one type of intermittent fasting (IF) called every-other-day feeding (EODF) on young animals is scarce. In this study, 1-month-old mice of both sexes were subjected to a 4-week regimen of EODF using age-matched counterparts fed ad libitum as controls. At the end of EODF exposure, experimental male and female mice weighed 14 and 13% less than the control counterparts. The EODF regimen resulted in lower liver levels of glycogen, glucose, and lactate, but did not affect lactate level in mouse cerebral cortex of both sexes. Activities of key glycolytic enzymes (hexokinase, phosphofructokinase, and pyruvate kinase) in liver of experimental mice were lower than those in controls. In the cerebral cortex, only hexokinase and pyruvate kinase activities were lower than in controls, but phosphofructokinase activity was not affected in IF females and was higher in IF males as compared with ad libitum fed males. Mitochondria isolated from liver of IF mice had lower respiratory control ratios, but those from the cortex had the same values as control animals. The concentration of β-hydroxybutyrate and the activity of β-hydroxybutyrate dehydrogenase were lower in the IF mouse liver, but not changed or enhanced in the IF cerebral cortex. Thus, animal responses to IF do not depend significantly on sex and are directed to decrease energy metabolism to save resources, and the effects are more pronounced in the liver than in the brain.

Oxidative Stress and Energy Metabolism in the Brain: Midlife as a Turning Point

“…Despite an intensive oxidative metabolism, no highly efficient brain-specific ROS defense systems were described so far. Surprisingly, however, the levels of ROS-mediated lipid/protein oxidation products in the brain are comparable to those found in other organs [ 25 , 68 ].…”

Intermittent and periodic fasting, longevity and disease

“…IF lasting between 12 and 24 hours can also have effects on IGF-1, IGFBP-1, glucose and ketone bodies, but most of the changes are smaller than those obtained by the longer PF or the chronic CR. For example, in mice, 4 weeks of every-other-day IF did not elevate ketone bodies but instead caused a reduction in β-hydroxybutyrate levels and β-hydroxybutyrate dehydrogenase activity in the mouse liver but not in the cerebral cortex, where levels remained unchanged or enhanced, supporting the importance of further investigating the mechanisms of ketone-body production, release and delivery 102 . However, circulating IGF-1, insulin and glucose were decreased after resistance-trained men (aged 29-33 and weighing 85-92 kg)…”

Feeding to satiation induces mild oxidative/carbonyl stress in the brain of young mice

“…We used young mice (4 weeks old) that were subjected for four weeks to regimens of either ad libitum (AL) feeding (control) or intermittent fasting applied as EODF (experimental). Animal body mass characteristics and data about food consumption during the experiment were provided in our previous study (Sorochynska et al, 2019[ 45 ]). Briefly, at the final stage on the experiment on average, AL males consumed 27 % more calories than their EODF counterparts (12.2 kcal/day AL and vs 8.9 kcal/day EODF), whereas AL females consumed 25 % more calories than their EODF counterparts (10.5 kcal/day AL and vs 7.8 kcal/day EODF) which well corresponds to literature data for AL groups (List et al, 2013[ 17 ]; Yang et al, 2014[ 53 ]).…”

“…Briefly, at the final stage on the experiment on average, AL males consumed 27 % more calories than their EODF counterparts (12.2 kcal/day AL and vs 8.9 kcal/day EODF), whereas AL females consumed 25 % more calories than their EODF counterparts (10.5 kcal/day AL and vs 7.8 kcal/day EODF) which well corresponds to literature data for AL groups (List et al, 2013[ 17 ]; Yang et al, 2014[ 53 ]). EODF mice were significantly lighter than controls by 14 and 13 % for males and females, respectively (Sorochynska et al, 2019[ 45 ]; Supplementary Figure 1). These data collectively clearly testify that EODF animals of both sexes were dietary restricted to virtually the same extent.…”

“…The advantage of such EODF protocol includes: ( i ) the ability to keep animals within their social group in order to avoid stress which animals are subjected at individual housing and ( ii ) free and ad libitum access to food on the feeding day, so that each mouse may consume forage without competing or fighting. Earlier we reported that at this design experimental mice of both sexes were dietary restricted (Sorochynska et al, 2019[ 45 ]).…”