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Diurnal expression of Dgat2 induced by time‐restricted feeding maintains cardiac health in the Drosophila model of circadian disruption
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Diurnal expression of Dgat2 induced by time‐restricted feeding maintains cardiac health in the Drosophila model of circadian disruption
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Journal Article
Diurnal expression of Dgat2 induced by time‐restricted feeding maintains cardiac health in the Drosophila model of circadian disruption
2024
Overview
Circadian disruption is associated with an increased risk of cardiometabolic disorders and cardiac diseases. Time‐restricted feeding/eating (TRF/TRE), restricting food intake within a consistent window of the day, has shown improvements in heart function from flies and mice to humans. However, whether and how TRF still conveys cardiac benefits in the context of circadian disruption remains unclear. Here, we demonstrate that TRF sustains cardiac performance, myofibrillar organization, and regulates cardiac lipid accumulation in Drosophila when the circadian rhythm is disrupted by constant light. TRF induces oscillations in the expression of genes associated with triglyceride metabolism. In particular, TRF induces diurnal expression of diacylglycerol O‐acyltransferase 2 (Dgat2), peaking during the feeding period. Heart‐specific manipulation of Dgat2 modulates cardiac function and lipid droplet accumulation. Strikingly, heart‐specific overexpression of human Dgat2 at ZT 0–10 significantly improves cardiac performance in flies exposed to constant light. We have demonstrated that TRF effectively attenuates cardiac decline induced by circadian disruption. Moreover, our data suggests that diurnal expression of Dgat2 induced by TRF is beneficial for heart health under circadian disruption. Overall, our findings have underscored the relevance of TRF in preserving heart health under circadian disruptions and provided potential targets, such as Dgat2, and strategies for therapeutic interventions in mitigating cardiac aging, metabolic disorders, and cardiac diseases in humans. TRF mitigates aging and circadian rhythm disruption cardiac dysfunction including maintaining myofibrillar organization and lipid metabolism. TRF induces the expression rhythmicity of genes linked with triglyceride metabolism and induces diurnal expression of Dgat2 with peak expression during the feeding phase under circadian rhythm disruption. Diurnal expression Overexpression of hDgat2 improves cardiac function under circadian disruption.
Publisher
John Wiley & Sons, Inc
Subject
/ Animals
/ Circadian Rhythm - physiology
/ Dgat2
/ Diacylglycerol O-acyltransferase
/ Diacylglycerol O-Acyltransferase - genetics
/ Diacylglycerol O-Acyltransferase - metabolism
/ Diurnal
/ Drosophila melanogaster - metabolism
/ Drosophila Proteins - genetics
/ Drosophila Proteins - metabolism
/ Females
/ Food
/ Humans
/ Insects
/ Light
/ Lipids
