chronic circadian desynchronizationn of feeding-fasting rhythm generates alterations in daily glycemia, LDL, cholesterolemia and microbiota composition in mice

LAURA TREBUCQ; MELISA LAMBERTI; ROSANA ROTA; CRISTINA BORIO; BILEN MARCOS; DIEGO GOLOMBEK; SANTIAGO PLANO; JUAN JOSE CHIESA

Frontiers in nutrition

Frontiers

Lugar: Lausanne; Año: 2023

The circadian system synchronizes behavior and physiology to the 24-h light–dark (LD) cycle. Timing of food intake and fasting periods provide strong signalsfor peripheral circadian clocks regulating nutrient assimilation, glucose, and lipidmetabolism. Mice under 12 h light:12 h dark (LD) cycles exhibit behavioral activityand feeding during the dark period, while fasting occurs at rest during light.Disruption of energy metabolism, leading to an increase in body mass, was reportedin experimental models of circadian desynchronization. In this work, the effectsof chronic advances of the LD cycles (chronic jet-lag protocol, CJL) were studiedon the daily homeostasis of energy metabolism and weight gain. Mice under CJLshow behavioral desynchronization and feeding activity distributed similarly atthe light and dark hours and, although feeding a similar daily amount of food ascompared to controls, show an increase in weight gain. In addition, ad libitumglycemia rhythm was abolished in CJL-subjected mice, showing similar bloodglucose values at light and dark. CJL also generated glucose intolerance at darkin an intraperitoneal glucose tolerance test (IPGTT), with increased insulin releaseat both light and dark periods. Low-density lipoprotein (LDL) cholesterolemiawas increased under this condition, but no changes in HDL cholesterolemia wereobserved. Firmicutes/Bacteroidetes ratio was analyzed as a marker of circadiandisruption of microbiota composition, showing opposite phases at the lightand dark when comparing LD vs. CJL. In conclusion, chronic misalignment offeeding/fasting rhythm leads to metabolic disturbances generating nocturnalhyperglycemia, glucose intolerance and hyperinsulinemia in a IPGTT, increasedLDL cholesterolemia, and increased weight gain, underscoring the importanceof the timing of food consumption with respect to the circadian system formetabolic health.