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.
Highlights
Under unlimited access to food, all animals including humans tend to consume excess of food that is poorly controlled due to a natural instinct to accumulate fuel reserves for use in times of food scarcity (La Fleur et al, 2014; Harris et al, 2018)
Phenylmethylsulfonyl fluoride (PMSF), KH2PO4, NaCl, ethylenediamine tetraacetic acid (EDTA), ATP, ADP, MgCl2, β-hydroxybutyrate, phosphoenolpyruvate, sodium L-lactate, sodium pyruvate, imidazole, hydrazine, aldolase, triosephosphate isomerase, glyceraldehyde 3-phosphate dehydrogenase, fructose 6-phosphate, glucose 6-phosphate, glucose, Glucose-6-phosphate dehydrogenase (G6PDH), КСl, mannitol, bovine serum albumin, glutamate, malate, rotenone, succinate, antimycin A, ascorbate, N,N,N′,N′-tetramethyl-pphenylenediamine (TMPD), and NaN3 were purchased from Sigma-Aldrich
Males of control and every-other-day feeding regimen (EODF) groups virtually doubled their masses, whereas females demonstrated ~1.5-fold increase (Figures 1A,B) and this well corresponds to data from The Jackson Laboratory
Summary
Under unlimited access to food, all animals including humans tend to consume excess of food that is poorly controlled due to a natural instinct to accumulate fuel reserves for use in times of food scarcity (La Fleur et al, 2014; Harris et al, 2018). Food intake reduced relative to an ad libitum (AL) diet is called dietary restriction (DR) and was found to extend mean and maximum life span and health span in a variety of organisms, ranging from bacteria to humans, and is beneficial in relieving diverse age-related pathologies (Mattson et al, 2017; Xie et al, 2017). Such restriction has been found to decrease body mass and normalize blood glucose, insulin, and leptin levels in obese animals and humans helping at metabolic diseases including metabolic syndrome. In addition to effects on peripheral tissues, DR improves the operation of the central nervous system and weakens the symptoms of age-related neurodegenerative disorders in rodent models (Mattson et al, 2017)
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