Quantitative analysis of light-phase restricted feeding reveals metabolic dyssynchrony in mice.
BACKGROUND
Considerable evidence suggests that the time of day at which calories are consumed markedly impacts body weight gain and adiposity. However, a precise quantification of energy balance parameters during controlled animal studies enforcing time-of-day-restricted feeding is currently lacking in the absence of direct human interaction.


OBJECTIVE
The purpose of the present study was therefore to quantify the effects of restricted feeding during the light (sleep)-phase in a fully-automated, computer-controlled comprehensive laboratory animal monitoring system (CLAMS) designed to modulate food access in a time-of-day-dependent manner. Energy balance, gene expression (within metabolically relevant tissues), humoral factors and body weight were assessed.


RESULTS
We report that relative to mice fed only during the dark (active)-phase, light (sleep)-phase fed mice: (1) consume a large meal upon initiation of food availability; (2) consume greater total calories per day; (3) exhibit a higher respiratory exchange ratio (indicative of decreased reliance on lipid/fatty acid oxidation); (4) exhibit tissue-specific alterations in the phases and amplitudes of circadian clock and metabolic genes in metabolically active tissues (greatest phase differences observed in the liver and diminution of amplitudes in epididymal fat, gastrocnemius muscle and heart); (5) exhibit diminished amplitude in humoral factor diurnal variations (for example, corticosterone); and (6) exhibit greater weight gain within 9 days of restricted feeding.


CONCLUSIONS
Collectively, these data suggest that weight gain following light (sleep)-phase restricted feeding is associated with significant alterations in energy balance, as well as dyssynchrony between metabolically active organs.
Department of Epidemiology, University of Alabama at Birmingham, Birmingham, AL 35294, USA.
M S
MS
Bray
W F
WF
Ratcliffe
M H
MH
Grenett
R A
RA
Brewer
K L
KL
Gamble
M E
ME
Young
D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D001786:Blood Glucose / Q000378:metabolism; D001835:Body Weight; D056926:CLOCK Proteins / Q000378:metabolism*; D057906:Circadian Clocks; D002940:Circadian Rhythm / Q000502:physiology*; D003345:Corticosterone / Q000378:metabolism; D002149:Energy Intake; D004734:Energy Metabolism / Q000502:physiology*; D005247:Feeding Behavior / Q000502:physiology*; D015870:Gene Expression; D008027:Light; D008297:Male; D051379:Mice; D009043:Motor Activity; D014280:Triglycerides / Q000378:metabolism
D015415:Biomarkers; D001786:Blood Glucose; D014280:Triglycerides; D056926:CLOCK Proteins; D003345:Corticosterone