| dc.description | Abstract: Introduction: The circadian system synchronizes behavior and physiology to the
24-h light– dark (LD) cycle. Timing of food intake and fasting periods provide
strong signals for peripheral circadian clocks regulating nutrient assimilation,
glucose, and lipid metabolism. Mice under 12h light:12h dark (LD) cycles exhibit
behavioral activity and feeding during the dark period, while fasting occurs at rest
during light. Disruption of energy metabolism, leading to an increase in body mass,
was reported in experimental models of circadian desynchronization. In this work,
the effects of chronic advances of the LD cycles (chronic jet-lag protocol, CJL)
were studied on the daily homeostasis of energy metabolism and weight gain.
Methods: Male C57 mice were subjected to a CJL or LD schedule, measuring
IPGTT, insulinemia, microbiome composition and lipidemia.
Results: Mice under CJL show behavioral desynchronization and feeding activity
distributed similarly at the light and dark hours and, although feeding a similar daily
amount of food as compared to controls, show an increase in weight gain. In addition,
ad libitum glycemia rhythm was abolished in CJL-subjected mice, showing similar blood
glucose values at light and dark. CJL also generated glucose intolerance at dark in an
intraperitoneal glucose tolerance test (IPGTT), with increased insulin release at both light
and dark periods. Low-density lipoprotein (LDL) cholesterolemia was increased under
this condition, but no changes in HDL cholesterolemia were observed. Firmicutes/
Bacteroidetes ratio was analyzed as a marker of circadian disruption of microbiota
composition, showing opposite phases at the light and dark when comparing LD vs. CJL.
Discussion: Chronic misalignment of feeding/fasting rhythm leads to metabolic
disturbances generating nocturnal hyperglycemia, glucose intolerance and
hyperinsulinemia in a IPGTT, increased LDL cholesterolemia, and increased
weight gain, underscoring the importance of the timing of food consumption
with respect to the circadian system for metabolic health. | |
