Intermittent fasting does not affect whole-body glucose, lipid, or protein metabolism.
BACKGROUND
Intermittent fasting (IF) was shown to increase whole-body insulin sensitivity, but it is uncertain whether IF selectively influences intermediary metabolism. Such selectivity might be advantageous when adapting to periods of food abundance and food shortage.


OBJECTIVE
The objective was to assess effects of IF on intermediary metabolism and energy expenditure.


METHODS
Glucose, glycerol, and valine fluxes were measured after 2 wk of IF and a standard diet (SD) in 8 lean healthy volunteers in a crossover design, in the basal state and during a 2-step hyperinsulinemic euglycemic clamp, with assessment of energy expenditure and phosphorylation of muscle protein kinase B (AKT), glycogen synthase kinase (GSK), and mammalian target of rapamycine (mTOR). We hypothesized that IF selectively increases peripheral glucose uptake and lowers proteolysis, thereby protecting protein stores.


RESULTS
No differences in body weight were observed between the IF and SD groups. Peripheral glucose uptake and hepatic insulin sensitivity during the clamp did not significantly differ between the IF and SD groups. Likewise, lipolysis and proteolysis were not different between the IF and SD groups. IF decreased resting energy expenditure. IF had no effect on the phosphorylation of AKT but significantly increased the phosphorylation of glycogen synthase kinase. Phosphorylation of mTOR was significantly lower after IF than after the SD.


CONCLUSIONS
IF does not affect whole-body glucose, lipid, or protein metabolism in healthy lean men despite changes in muscle phosphorylation of GSK and mTOR. The decrease in resting energy expenditure after IF indicates the possibility of an increase in weight during IF when caloric intake is not adjusted. This study was registered at www.trialregister.nl as NTR1841.
Soeters
Maarten R
MR
Department of Endocrinology and Metabolism, University of Amsterdam, Amsterdam, Netherlands. m.r.soeters@amc.uva.nl
Lammers
Nicolette M
NM
Dubbelhuis
Peter F
PF
Ackermans
Mariëtte
M
Jonkers-Schuitema
Cora F
CF
Fliers
Eric
E
Sauerwein
Hans P
HP
Aerts
Johannes M
JM
Serlie
Mireille J
MJ
D000293:Adolescent; D000328:Adult; D001835:Body Weight; D004032:Diet; D002149:Energy Intake; D004734:Energy Metabolism; D005215:Fasting / Q000502:physiology*; D005947:Glucose / Q000378:metabolism*; D015309:Glucose Clamp Technique; D038341:Glycogen Synthase Kinases / Q000378:metabolism; D006801:Humans; D050356:Lipid Metabolism; D008297:Male; D018482:Muscle, Skeletal / Q000201:enzymology; D018579:Patient Selection; D011494:Protein Kinases / Q000378:metabolism; D011506:Proteins / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D058570:TOR Serine-Threonine Kinases; D013997:Time Factors; D055815:Young Adult
D011506:Proteins; D011494:Protein Kinases; C546842:MTOR protein, human; D038341:Glycogen Synthase Kinases; D051057:Proto-Oncogene Proteins c-akt; D058570:TOR Serine-Threonine Kinases; D005947:Glucose