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Altered circadian rhythm and metabolic gene profile in rats subjected to advanced light phase shifts.

ABSTRACT: The circadian clock regulates metabolic homeostasis and its disruption predisposes to obesity and other metabolic diseases. However, the effect of phase shifts on metabolism is not completely understood. We examined whether alterations in the circadian rhythm caused by phase shifts induce metabolic changes in crucial genes that would predispose to obesity. Three-month-old rats were maintained on a standard diet under lighting conditions with chronic phase shifts consisting of advances, delays or advances plus delays. Serum leptin, insulin and glucose levels decreased only in rats subjected to advances. The expression of the clock gene Bmal 1 increased in the hypothalamus, white adipose tissue (WAT), brown adipose tissue (BAT) and liver of the advanced group compared to control rats. The advanced group showed an increase in hypothalamic AgRP and NPY mRNA, and their lipid metabolism gene profile was altered in liver, WAT and BAT. WAT showed an increase in inflammation and ER stress and brown adipocytes suffered a brown-to-white transformation and decreased UCP-1 expression. Our results indicate that chronic phase advances lead to significant changes in neuropeptides, lipid metabolism, inflammation and ER stress gene profile in metabolically relevant tissues such as the hypothalamus, liver, WAT and BAT. This highlights a link between alteration of the circadian rhythm and metabolism at the transcriptional level.

SUBMITTER: Herrero L

PROVIDER: S-EPMC4383616 | biostudies-literature | 2015

REPOSITORIES: biostudies-literature

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Altered circadian rhythm and metabolic gene profile in rats subjected to advanced light phase shifts.

Herrero Laura L Valcarcel Lorea L da Silva Crhistiane Andressa CA Albert Nerea N Diez-Noguera Antoni A Cambras Trinitat T Serra Dolors D

PloS one 20150402 4

The circadian clock regulates metabolic homeostasis and its disruption predisposes to obesity and other metabolic diseases. However, the effect of phase shifts on metabolism is not completely understood. We examined whether alterations in the circadian rhythm caused by phase shifts induce metabolic changes in crucial genes that would predispose to obesity. Three-month-old rats were maintained on a standard diet under lighting conditions with chronic phase shifts consisting of advances, delays or ...[more]

PMID: 25837425

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Project description:The circadian rhythm, called Process C, regulates a wide range of biological processes in humans including sleep, metabolism, body temperature, and hormone secretion. Light is the dominant synchronizer of the circadian rhythm-it has been used to regulate the circadian phase to cope with jet-lag, shift work, and sleep disorder. The homeostatic oscillation of the sleep drive is called Process S. Process C and Process S together determine the sleep-wake cycle in what is known as the two-process model. This paper addresses the regulation of both Process C and Process S by scheduling light exposure and sleep based on numerical simulations of circadian rhythm and sleep mathematical models. This is a significant step beyond the existing literature that only considers the entrainment of Process C. Regulation of the two-process model poses several unique features and challenges: 1. Process S is non-smooth, i.e., the homeostatic dynamics are different in the sleep and wake regimes; 2. Light only indirectly affects Process S through Process C; 3. Light does not affect Process C during sleep. We consider two scenarios: optimizing light intensity as the control input with spontaneous (i.e., unscheduled) sleep/wake times and jointly optimizing the light intensity and the sleep/wake times, which allows limited delayed sleep and early waking as part of the decision variables. We solve the time-optimal entrainment problem for the two-process model for both scenarios using an extension of the gradient descent algorithm to non-smooth systems. To illustrate the efficacy of our time-optimal entrainment strategies, we consider two common use cases: transmeridian travelers and shift workers. For transmeridian travelers, joint optimization of the two-process model avoids the unrealistic long wake duration when only Process C is considered. The entrainment time also decreases when both the light input and the sleep schedule are optimized compared to when only the light input is optimized. For shift workers, we show that the entrainment time is significantly shortened by optimizing the night shift working light.

Project description:The circadian rhythm of gut microbiota is an important biological rhythm that plays a crucial role in host health. However, few studies have determined the associations between the circadian rhythm and gut microbiota in laying hens. The present experiment investigated the circadian rhythm of fecal microbiota in laying hens. Feces samples were collected from 10 laying hens at nine different time points (06:00-12:00-18:00-00:00-06:00-12:00-18:00-00:00-06:00) to demonstrate the circadian rhythm of fecal microbiota. The results showed that the α and β diversity of the fecal microbiota fluctuated significantly at different time points. Beta nearest taxon index analysis suggested that assembly strategies of the abundant and rare amplicon sequence variant (ASV) sub-communities were different. Abundant ASVs preferred dispersal limitation (weak selection), and rare ASVs were randomly formed due to the "non-dominant" fractions. Highly robust fluctuations of fecal microbiota at the phylum level were found. For example, Firmicutes and Proteobacteria fluctuated inversely to each other, but the total ratio remained in a dynamic balance over 48 h. We identified that temporal dynamic changes had a significant effect on the relative abundance of the important bacteria in the feces microbial community using the random forest algorithm. Eight bacteria, Ruminococcus gnavus, Faecalibacterium, Ruminococcaceae, Enterococcus cecorum, Lachnospiraceae, Clostridium, Clostridiales, and Megamonas, showed significant changes over time. One unexpected finding was the fact that these eight bacteria belong to Firmicutes. The pathways showed significant fluctuation, including xenobiotic biodegradation and metabolism, carbohydrate metabolism, and amino acid metabolism, which were consistent with the metabolic functions of amino acids and carbohydrates from the feed. This study showed that the defecation time may be an important factor in the diversity, proportion, and functions of the feces microbial community. However, there was no circadian rhythm of microbial community assembly confirmed by JTK_Cycle analysis. These results might suggest there was no obvious circadian rhythm of fecal microbiota in laying hens under common light.

Dataset Information

Altered circadian rhythm and metabolic gene profile in rats subjected to advanced light phase shifts.

Publications

Altered circadian rhythm and metabolic gene profile in rats subjected to advanced light phase shifts.

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