Disrupted daily light-dark cycle induces the expression of hepatic gluconeogenic regulatory genes and hyperglycemia with glucose intolerance in mice.

We elucidated associations between metabolic disorders and the environmental light-dark (LD) cycle that entrains the circadian clock located in the suprachiasmatic nucleus of mammals. Mice were fed with a high-fat/high-sucrose diet for eight weeks under a normal 12h light-12h dark cycle (LD 12:12) or an ultradian 3h light-3h dark cycle (LD 3:3) that might perturb the central clock. The circadian behavioral rhythms were gradually disturbed under LD 3:3. Hyperglycemia with glucose intolerance and increases in diabetic markers, glycated albumin and hemoglobin A1c, were significantly induced without affecting body weight gain and food consumption in LD 3:3. Expression levels of hepatic gluconeogenic regulatory genes such as Pck1, G6pc, Hnf4a, and Foxo1/3/4 genes were increased under LD 3:3. Hypercholesterolemia with hepatic cholesterol accumulation was also induced in LD 3:3. Ultradian LD 3:3 cycles did not affect the adipose inflammation that is considered a major player in obesity-associated metabolic disorders. Our findings provide a link between metabolic disorders and environmental photoperiodic cycles in genetically normal animals.