Food in synchrony with melatonin and corticosterone relieves constant light disturbed metabolism
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Circadian disruption is associated with metabolic disturbances such as hepatic steatosis (HS), obesity and type 2 diabetes. We hypothesized that HS, resulting from constant light (LL) exposure is due to an inconsistency between signals related to food intake and endocrine-driven suprachiasmatic nucleus (SCN) outputs. Indeed, exposing rats to LL induced locomotor, food intake and hormone arrhythmicity together with the development of HS. We investigated whether providing temporal signals such as 12-h food availability or driving a corticosterone plus melatonin rhythm could restore rhythmicity and prevent the metabolic disturbances under LL conditions in male rats. Discrete metabolic improvements under these separate treatments stimulated us to investigate whether the combination of hormone treatment together with mealtime restriction (12-h food during four weeks) could prevent the metabolic alterations. LL exposed arrhythmic rats, received daily administration of corticosterone (2.5 μg/kg) and melatonin (2.5 mg/kg) in synchrony or out of synchrony with their 12-h meal. HS and other metabolic alterations were importantly ameliorated in LL-exposed rats receiving hormonal treatment in synchrony with 12-h restricted mealtime, while treatment out of phase with meal time did not. Interestingly, liver bile acids, a major indication for HS, were only normalized when animals received hormones in synchrony with food indicating that disrupted bile acid metabolism might be an important mechanism for the HS induction under LL conditions. We conclude that food-elicited signals, as well as hormonal signals, are necessary for liver synchronization and that HS arises when there is conflict between food intake and the normal pattern of melatonin and corticosterone. © 2017 Society for Endocrinology Printed in Great Britain.
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circadian disruption; Corticosterone; Food restriction; liver; Melatonin; Metabolic alterations bile acid; corticosterone; insulin; melatonin; triacylglycerol; corticosterone; melatonin; animal experiment; animal model; animal tissue; Article; bile acid metabolism; body weight; circadian rhythm; controlled study; diet restriction; fatty liver; feeding behavior; food availability; food deprivation; food intake; glucose homeostasis; glucose tolerance test; hormonal therapy; hyperglycemia; hyperinsulinemia; insulin level; intra-abdominal fat; light dark cycle; light exposure; lipid liver level; lipid metabolism; lipid storage; locomotion; male; metabolic disorder; nonhuman; obesity; priority journal; rat; subcutaneous fat; suprachiasmatic nucleus; adverse effects; animal; Chronobiology Disorders; complication; drug effects; fatty liver; Glucose Metabolism Disorders; light; metabolism; pathophysiology; Wistar rat; Adiposity; Animals; Chronobiology Disorders; Corticosterone; Fatty Liver; Feeding Methods; Glucose Metabolism Disorders; Light; Male; Melatonin; Rats, Wistar; Suprachiasmatic Nucleus
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