Reprogramming of the Circadian Clock by Nutritional Challenge

Eckel‐Mahan, Kristin; Patel, Vishal R.; Mateo, Sara de; Orozco-Solís, Ricardo; Ceglia, Nicholas; Sahar, Saurabh; Dilag-Penilla, Sherry A.; Dyar, Kenneth A.; Baldi, Pierre; Sassone–Corsi, Paolo

doi:10.1016/j.cell.2013.11.034

Cited by 569 publications

(613 citation statements)

References 75 publications

Supporting

Mentioning

555

Contrasting

Unclassified

Order By: Relevance

“…The gain of rhythmicity in these micro-RNAs could impact the cyclic expression of a whole host of proteins, perhaps leading to a novel, compensatory clock that is activated when the canonical clock breaks down. A recent study by Eckel-Mahan et al (58) had a similar finding in the liver of mice fed a high-fat diet. Mice on regular chow showed normal cycling of canonical circadian genes in the liver and the rhythms in these genes were severely disrupted with a high-fat diet.…”

Section: Discussionsupporting

confidence: 61%

Effects of aging on circadian patterns of gene expression in the human prefrontal cortex

Chen

Logan

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

216

212

View full text Add to dashboard Cite

With aging, significant changes in circadian rhythms occur, including a shift in phase toward a “morning” chronotype and a loss of rhythmicity in circulating hormones. However, the effects of aging on molecular rhythms in the human brain have remained elusive. Here, we used a previously described time-of-death analysis to identify transcripts throughout the genome that have a significant circadian rhythm in expression in the human prefrontal cortex [Brodmann’s area 11 (BA11) and BA47]. Expression levels were determined by microarray analysis in 146 individuals. Rhythmicity in expression was found in ∼10% of detected transcripts (P < 0.05). Using a metaanalysis across the two brain areas, we identified a core set of 235 genes (q < 0.05) with significant circadian rhythms of expression. These 235 genes showed 92% concordance in the phase of expression between the two areas. In addition to the canonical core circadian genes, a number of other genes were found to exhibit rhythmic expression in the brain. Notably, we identified more than 1,000 genes (1,186 in BA11; 1,591 in BA47) that exhibited age-dependent rhythmicity or alterations in rhythmicity patterns with aging. Interestingly, a set of transcripts gained rhythmicity in older individuals, which may represent a compensatory mechanism due to a loss of canonical clock function. Thus, we confirm that rhythmic gene expression can be reliably measured in human brain and identified for the first time (to our knowledge) significant changes in molecular rhythms with aging that may contribute to altered cognition, sleep, and mood in later life.

show abstract

Section: Discussionsupporting

confidence: 61%

Effects of aging on circadian patterns of gene expression in the human prefrontal cortex

Chen

Logan

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

216

212

View full text Add to dashboard Cite

show abstract

“…This pattern of clock-controlled gene dysregulation by a HFD has been reported in the liver (31). The mechanism involved disruption of Bmal1 association with the chromatin in situ without any significant changes in Bmal1 RNA and/or protein levels (31).…”

Section: Discussionmentioning

confidence: 99%

“…The core players of this molecular transcriptional feedback system, which orchestrates the cyclic expression of clock-controlled genes, are Clock (circadian locomotor output cycles kaput), Bmal1 (brain and muscle ARNT-like 1), Period proteins Per1-3, two Cry (Cryptochrome) proteins, and Rev-erb␣ (28 -30). This sophisticated and elegant transcriptional clock machinery ensures coordinated and orchestrated molecular and physiological responses by affecting target gene expression with changes in the environment, for example, through changes in diet (31).…”

mentioning

confidence: 99%

Evidence for a Circadian Effect on the Reduction of Human Growth Hormone Gene Expression in Response to Excess Caloric Intake

Vakili¹,

Jin

Cattini

2016

Journal of Biological Chemistry

View full text Add to dashboard Cite

Rhythmicity of biological functions is fundamental for optimal adaptations to environmental cues. Growth hormone (GH) is a major metabolic homeostatic factor that is secreted with a circadian pattern, but whether it is synthesized rhythmically is unknown. We used transgenic mice containing the human (h) GH gene (hGH1) locus to investigate the rhythmicity of hGH synthesis and secretion and to show that RNA and secreted protein levels oscillate over a 24-h cycle. Analysis of hGH1 promoter sequences revealed an enhancer motif (E-box) element that binds the circadian transcriptional machinery (Bmal1 and Clock). Furthermore, Bmal1/Clock were able to transactivate the hGH1 promoter, and mutation of this E-box element adversely affected basal activity after gene transfer. The ability of Bmal1 to bind the hGH1 promoter region containing the E-box element was confirmed in the hGH1 transgenic mouse pituitary in situ. Occupancy was reduced in mice fed a high fat diet during the light (inactive) stage of the daily cycle in mice and corresponded to a decrease in hGH1 RNA levels. The decreases in occupancy and RNA levels were not seen, however, during the dark (active) stage. A chromatin loop required for efficient postnatal hGH1 expression was negatively affected by the high fat diet in the light but not dark stage similar to the pattern observed with Bmal1 association with the promoter region. This is the first evidence that hGH synthesis follows a diurnal rhythm and of dynamic associations of the circadian machinery with a component of a chromosomal structure of the hGH1 locus that is essential for efficient expression.

show abstract

“…Consistent with studies in human subjects (108) , TAG species were especially rhythmic, but their peak accumulation was shifted in clock gene-deficient animals (112) . Exposure to a high-fat diet also has a profound influence on diurnal variation in the liver metabolome (82,113) . Although a similar percentage of metabolites exhibit diurnal oscillations in animals fed a high-fat diet v. normal chow (about 30 %), there are dietdependent differences in the phase and amplitude of many metabolite rhythms (113) .…”

Section: Using Lipidomics To Characterise Metabolic Pathwaysmentioning

confidence: 99%

“…Exposure to a high-fat diet also has a profound influence on diurnal variation in the liver metabolome (82,113) . Although a similar percentage of metabolites exhibit diurnal oscillations in animals fed a high-fat diet v. normal chow (about 30 %), there are dietdependent differences in the phase and amplitude of many metabolite rhythms (113) . Interestingly, a high-fat diet induces diurnal oscillations for a substantial number of transcripts, and this is largely dependent on PPARγ-mediated gene transcription.…”

Section: Using Lipidomics To Characterise Metabolic Pathwaysmentioning

confidence: 99%

Circadian regulation of lipid metabolism

Gooley

2016

Proc. Nutr. Soc.

128

View full text Add to dashboard Cite

The circadian system temporally coordinates daily rhythms in feeding behaviour and energy metabolism. The objective of the present paper is to review the mechanisms that underlie circadian regulation of lipid metabolic pathways. Circadian rhythms in behaviour and physiology are generated by master clock neurons in the suprachiasmatic nucleus (SCN). The SCN and its efferent targets in the hypothalamus integrate light and feeding signals to entrain behavioural rhythms as well as clock cells located in peripheral tissues, including the liver, adipose tissue and muscle. Circadian rhythms in gene expression are regulated at the cellular level by a molecular clock comprising a core set of clock genes/proteins. In peripheral tissues, hundreds of genes involved in lipid biosynthesis and fatty acid oxidation are rhythmically activated and repressed by clock proteins, hence providing a direct mechanism for circadian regulation of lipids. Disruption of clock gene function results in abnormal metabolic phenotypes and impaired lipid absorption, demonstrating that the circadian system is essential for normal energy metabolism. The composition and timing of meals influence diurnal regulation of metabolic pathways, with food intake during the usual rest phase associated with dysregulation of lipid metabolism. Recent studies using metabolomics and lipidomics platforms have shown that hundreds of lipid species are circadian-regulated in human plasma, including but not limited to fatty acids, TAG, glycerophospholipids, sterol lipids and sphingolipids. In future work, these lipid profiling approaches can be used to understand better the interaction between diet, mealtimes and circadian rhythms on lipid metabolism and risk for obesity and metabolic diseases.

show abstract

Reprogramming of the Circadian Clock by Nutritional Challenge

Cited by 569 publications

References 75 publications

Effects of aging on circadian patterns of gene expression in the human prefrontal cortex

Effects of aging on circadian patterns of gene expression in the human prefrontal cortex

Evidence for a Circadian Effect on the Reduction of Human Growth Hormone Gene Expression in Response to Excess Caloric Intake

Circadian regulation of lipid metabolism

Contact Info

Product

Resources

About