Impact of Obesity on Day-Night Differences in Cardiac Metabolism
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ABSTRACT:
PROVIDER: PRJNA720636 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR14183540_1.fastq.gz | Fastqsanger.gz | |||
| SRR14183540_2.fastq.gz | Fastqsanger.gz | |||
| SRR14183541_1.fastq.gz | Fastqsanger.gz | |||
| SRR14183541_2.fastq.gz | Fastqsanger.gz | |||
| SRR14183542_1.fastq.gz | Fastqsanger.gz |
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Project description:An intrinsic property of the heart is an ability to rapidly and coordinately adjust flux through metabolic pathways in response to physiologic stimuli (termed metabolic flexibility). Cardiac metabolism also fluctuates across the 24-hr day, in association with diurnal sleep-wake and fasting-feeding cycles. Although loss of metabolic flexibility has been proposed to play a causal role in the pathogenesis of cardiac disease, it is currently unknown whether day-night variations in cardiac metabolism are altered during disease states. Here, we tested the hypothesis that diet-induced obesity disrupts cardiac “diurnal metabolic flexibility”, which is normalized by time-of-day-restricted feeding. Chronic high fat feeding (20-wk) induced obesity in mice, abolished diurnal rhythms in whole body metabolic flexibility, and increased markers of adverse cardiac remodeling (hypertrophy, fibrosis, and steatosis). RNAseq analysis revealed that 24-hr rhythms in the cardiac transcriptome were dramatically altered during obesity; only 22% of rhythmic transcripts in control hearts were unaffected by obesity. However, day-night differences in cardiac substrate oxidation were essentially identical in control and high fat fed mice. In contrast, day-night differences in both cardiac triglyceride synthesis and lipidome were abolished during obesity. Next, a subset of obese mice (induced by 18-wks ad libitum high fat feeding) were allowed access to the high fat diet only during the 12-hr dark (active) phase, for a 2-wk period. Dark phase restricted feeding partially restored whole body metabolic flexibility, as well as day-night differences in cardiac triglyceride synthesis and lipidome. Moreover, this intervention partially reversed adverse cardiac remodeling in obese mice. Collectively, these studies reveal diurnal metabolic inflexibility of the heart during obesity specifically for non-oxidative lipid metabolism (but not for substrate oxidation), and that restricting food intake to the active period partially reverses obesity-induced cardiac lipid metabolism abnormalities and adverse remodeling of the heart.
2021-04-09 | GSE171710 | GEO
Project description:An intrinsic property of the heart is an ability to rapidly and coordinately adjust flux through metabolic pathways in response to physiologic stimuli (termed metabolic flexibility). Cardiac metabolism also fluctuates across the 24-hours day, in association with diurnal sleep-wake and fasting-feeding cycles. Although loss of metabolic flexibility has been proposed to play a causal role in the pathogenesis of cardiac disease, it is currently unknown whether day-night variations in cardiac metabolism are altered during disease states. Here, we tested the hypothesis that diet-induced obesity disrupts cardiac "diurnal metabolic flexibility", which is normalized by time-of-day-restricted feeding. Chronic high fat feeding (20-wk)-induced obesity in mice, abolished diurnal rhythms in whole body metabolic flexibility, and increased markers of adverse cardiac remodeling (hypertrophy, fibrosis, and steatosis). RNAseq analysis revealed that 24-hours rhythms in the cardiac transcriptome were dramatically altered during obesity; only 22% of rhythmic transcripts in control hearts were unaffected by obesity. However, day-night differences in cardiac substrate oxidation were essentially identical in control and high fat fed mice. In contrast, day-night differences in both cardiac triglyceride synthesis and lipidome were abolished during obesity. Next, a subset of obese mice (induced by 18-wks ad libitum high fat feeding) were allowed access to the high fat diet only during the 12-hours dark (active) phase, for a 2-wk period. Dark phase restricted feeding partially restored whole body metabolic flexibility, as well as day-night differences in cardiac triglyceride synthesis and lipidome. Moreover, this intervention partially reversed adverse cardiac remodeling in obese mice. Collectively, these studies reveal diurnal metabolic inflexibility of the heart during obesity specifically for nonoxidative lipid metabolism (but not for substrate oxidation), and that restricting food intake to the active period partially reverses obesity-induced cardiac lipid metabolism abnormalities and adverse remodeling of the heart.
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Project description:Background: Global climate change, in particular the entailed predicted temperature increase, will noticeably affect plants vegetative and reproductive development. High temperatures alter the composition of the grapevine fruit, one of the most important fruits produced worldwide. This is leading to variable yield and quality, already observed in many growing regions in recent years. However, physiological processes underlying temperature response and tolerance of the grapevine fruit have hardly been investigated. Currently, all studies on fleshy fruits investigating their abiotic stress response on a molecular level were conducted during the day but possible night-specific variations were overlooked. The present study explores the grapevine fruit transcriptomic response at different developmental stages upon heat stress at day and night. Methodology/Principal Results: Short heat stresses (2 h) were applied at day and night to vines bearing clusters sequentially ordered according to the developmental stages along their vertical axis. The recently proposed microvine model was grown in climatic chambers in order to circumvent common constraints and biases introduced in field experiments with perennial vines. Post-véraison berry heterogeneity inside clusters was evaded upon constituting homogenous batches following organic acid and sugar measurements on individual berries. A whole genome transcriptomic approach was subsequently conducted using NimbelGen® 090918 12X microarrays (30K). Results revealed important differences in heat stress responsive pathways according to day or night treatment, in particular regarding genes within phenylpropanoid metabolism. Precise distinction of post-véraison stages led to a stage-specific detection of anthocyanin-related transcripts repressed by heat. Important modifications in cell wall-related processes as well as indications for a heat-induced delay of ripening and sugar accumulation were observed at véraison and reversed in later stages. Conclusion: This first day - night study on heat stress adaption of the grapevine berry shows that the transcriptome of fleshy fruits is differentially affected by abiotic stress at night. The present results emphasize the necessity to include different developmental stages and especially different time points in transcriptomic studies.
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