Circadian Clock Desynchronization and Insulin Resistance

Abstract

The circadian rhythm regulates biological processes that occur within 24 h in living organisms. It plays a fundamental role in maintaining biological functions and responds to several inputs, including food intake, light/dark cycle, sleep/wake cycle, and physical activity. The circadian timing system comprises a central clock located in the suprachiasmatic nucleus (SCN) and tissue-specific clocks in peripheral tissues. Several studies show that the desynchronization of central and peripheral clocks is associated with an increased incidence of insulin resistance (IR) and related diseases. In this review, we discuss the current knowledge of molecular and cellular mechanisms underlying the impact of circadian clock dysregulation on insulin action. We focus our attention on two possible mediators of this interaction: the phosphatases belonging to the pleckstrin homology leucine-rich repeat protein phosphatase family (PHLPP) family and the deacetylase Sirtuin1. We believe that literature data, herein summarized, suggest that a thorough change of life habits, with the return to synchronized food intake, physical activity, and rest, would doubtless halt the vicious cycle linking IR to dysregulated circadian rhythms. However, since such a comprehensive change may be incompatible with the demand of modern society, clarifying the pathways involved may, nonetheless, contribute to the identification of therapeutic targets that may be exploited to cure or prevent IR-related diseases.

Circadian Rhythms Disrupted by Light at Night and Mistimed Food Intake Alter Hormonal Rhythms and Metabolism

“…Chronic exposure to ALAN increases body mass and impairs glucose processing while maintaining equivalent caloric intake and locomotor activity patterns [ 169 ]. Insulin is another circulating hormone that is affected by ALAN and disrupted circadian rhythms, independent of food intake; although the precise mechanisms through which desynchronization of central and peripheral clocks contributes to insulin resistance has yet to be determined, a recent review of the literature [ 171 ] proposes two possible mediators of this interaction: the phosphatases belonging to the pleckstrin homology leucine-rich repeat protein phosphatase family and the deacetylase Sirtuin1 [ 172 ]. ALAN decreases glucose tolerance and insulin sensitivity in rodent models [ 168 , 173 ] and in human studies [ 174 ].…”

Post-traumatic stress disorder, dyssomnias, and metabolic syndrome

“…Фрагментація сну і переривчаста гіпоксія можуть підвищувати збудливість СНС, що супроводжується метаболічними порушеннями [67]. Занадто короткий сон знижує чутливість до інсуліну в адипоцитах і впливає на фосфорилювання серину/треонінкінази (Akt/протеїнкінази В), що здійснюється в інсуліновому сигнальному шляху [68]. Нарешті, занадто велика тривалість сну пов'язана з кількома факторами ризику захворюваності на МС, такими як депресія та низька фізична активність [63].…”

The Interconnection between Hepatic Insulin Resistance and Metabolic Dysfunction-Associated Steatotic Liver Disease—The Transition from an Adipocentric to Liver-Centric Approach

“…Central clock genes that regulate the biological function of circadian rhythm are period genes (PER1, PER2, and PER3), cryptochrome genes (CRY 1 and CRY2), BMAL1, CLOCK, and genes encoding nuclear receptor REV-ERB and ROR [20]. Misalignment between central and peripheral clocks seems to be the major underlying explanation for the association between circadian misalignment and impaired insulin signaling [21]. A recent study by Jouffe et al [22] suggested that disruption of BMAL1 activity significantly impacts the pathogenesis of metabolic and liver diseases.…”