Circadian Clocks and Feeding Time Regulate the Oscillations and Levels of Hepatic Triglycerides

Adamovich, Yaarit; Rousso-Noori, Liat; Zwighaft, Ziv; Neufeld-Cohen, Adi; Golik, Marina; Kraut-Cohen, Judith; Wang, Miao; Han, Xianlin; Asher, Gad

doi:10.1016/j.cmet.2013.12.016

Cited by 334 publications

(322 citation statements)

References 43 publications

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“…In another study, lipidomics analyses revealed that about 17 % of lipids showed circadian oscillations in wild-type mice and in Per1 −/− /Per2 −/− mice fed ad libitum. 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) .…”

Section: Using Lipidomics To Characterise Metabolic Pathwayssupporting

confidence: 84%

Circadian regulation of lipid metabolism

Gooley

2016

Proc. Nutr. Soc.

135

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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.

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Section: Using Lipidomics To Characterise Metabolic Pathwayssupporting

confidence: 84%

Circadian regulation of lipid metabolism

Gooley

2016

Proc. Nutr. Soc.

135

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“…6 I-L) of WT and PER1/2 null mice under the above-described conditions. In agreement with previous reports on clock-disrupted mice (11,16,32,33), Per1/2 −/− mice exhibited attenuated diurnal feeding rhythms and consumed more food during the light phase compared with WT mice (∼45% vs. ∼29% during the day and ∼55% vs. ∼71% during the night in PER1/2 null and WT mice, respectively). Short duration (i.e., 3 d) of high-fat diet in contrast to 6 wk of high-fat diet (38) did not significantly alter the daily feeding habits of WT mice.…”

Section: Diurnal Oscillations In Mitochondrial Respiration In Responssupporting

confidence: 80%

“…Clock-deficient mice (e.g., Clock mutant and Cry1/2 and Per1/2 double-KO mice) exhibit greatly attenuated diurnal feeding rhythms, because they consume more food during the light phase compared with WT mice (11,16,32,33). To examine whether feeding rhythms might play a role in the diurnal accumulation of CPT1 and PDH and consequently, mitochondrial respiration, we applied a nighttimerestricted feeding regimen on PER1/2 null mice.…”

Section: Diurnal Oscillations In Mitochondrial Respiration In Responsmentioning

confidence: 99%

“…The core clock molecular circuitry relies on interlocked transcription-translation feedback loops that generate daily oscillations of gene expression in cultured cells and living animals (7). Many transcriptomes (8)(9)(10)(11)(12)) and more recently, several proteomics (13)(14)(15) and metabolomics studies (16)(17)(18)(19)(20)(21) highlighted the pervasive circadian control of metabolism.…”

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confidence: 99%

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Circadian control of oscillations in mitochondrial rate-limiting enzymes and nutrient utilization by PERIOD proteins

Neufeld-Cohen

Robles

Aviram

et al. 2016

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

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205

192

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Mitochondria are major suppliers of cellular energy through nutrients oxidation. Little is known about the mechanisms that enable mitochondria to cope with changes in nutrient supply and energy demand that naturally occur throughout the day. To address this question, we applied MS-based quantitative proteomics on isolated mitochondria from mice killed throughout the day and identified extensive oscillations in the mitochondrial proteome. Remarkably, the majority of cycling mitochondrial proteins peaked during the early light phase. We found that rate-limiting mitochondrial enzymes that process lipids and carbohydrates accumulate in a diurnal manner and are dependent on the clock proteins PER1/2. In this conjuncture, we uncovered daily oscillations in mitochondrial respiration that peak during different times of the day in response to different nutrients. Notably, the diurnal regulation of mitochondrial respiration was blunted in mice lacking PER1/2 or on a high-fat diet. We propose that PERIOD proteins optimize mitochondrial metabolism to daily changes in energy supply/demand and thereby, serve as a rheostat for mitochondrial nutrient utilization.M itochondria serve as major suppliers of cellular energy through nutrient oxidation. One of the major challenges that mitochondria face is the adaptation to changes in nutrient supply and energy demand. An inability of mitochondria to deal with altered nutrient environment is associated with metabolic diseases, such as diabetes and obesity (1, 2).Mitochondria oxidize carbohydrates and lipids to generate ATP by a process known as oxidative phosphorylation. Pyruvate and fatty acids are transported from the cytoplasm into the mitochondrial matrix, where they are catabolized into acetyl CoA. Pyruvate is converted to acetyl CoA through the action of the pyruvate dehydrogenase complex (PDC), whereas fatty acids are oxidized through a cycle of reactions that trim two carbons at a time, generating one molecule of acetyl CoA in each cycle [i.e., fatty acid oxidation (FAO)]. The acetyl groups are then fed into the Krebs cycle for additional degradation, and the process culminates with the transfer of acetyl-derived high-energy electrons along the respiratory chain.Mounting evidence suggests that circadian clocks orchestrate our daily physiology and metabolism (3-6). The mammalian circadian timing system consists of a central pacemaker in the brain that is entrained by daily light-dark cycles and synchronizes subsidiary oscillators in virtually all cells of the body, in part by driving rhythmic feeding behavior. The core clock molecular circuitry relies on interlocked transcription-translation feedback loops that generate daily oscillations of gene expression in cultured cells and living animals (7). Many transcriptomes (8-12) and more recently, several proteomics (13-15) and metabolomics studies (16-21) highlighted the pervasive circadian control of metabolism.Rest-activity and feeding-fasting cycles that naturally occur throughout the day impose pronounced changes in nutrient s...

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“…RNA extraction and transcript quantification by real-time PCR were carried out as previously described (Adamovich et al, 2014). Synthesis of cDNA was done using qScript TM cDNA SuperMix (Quanta Biosciences).…”

Section: Rna Preparation and Real-time Pcr Analysismentioning

confidence: 99%

Rhythmic Oxygen Levels Reset Circadian Clocks through HIF1α

et al. 2017

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General rightsThis document is made available in accordance with publisher policies. Please cite only the published version using the reference above. AbstractThe mammalian circadian system consists of a master clock in the brain that synchronizes subsidiary oscillators in peripheral tissues. The master clock maintains phase coherence in peripheral cells through systemic cues such as feeding-fasting and temperature cycles. Here we examined the role of oxygen as a resetting cue for circadian clocks. We continuously measured oxygen levels in living animals and detected daily rhythms in tissue oxygenation. Oxygen cycles, within the physiological range, were sufficient to synchronize cellular clocks in HIF1α-dependent manner. Furthermore, several clock genes responded to changes in oxygen levels through HIF1α. Finally, we found that a moderate reduction in oxygen levels for a short period accelerates the adaptation of wild type but not of HIF1α-deficient mice to the new time in a jet lag protocol. We conclude that oxygen, via HIF1α activation, is a resetting cue for circadian clocks and propose oxygen modulation as therapy for jet lag.

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Circadian Clocks and Feeding Time Regulate the Oscillations and Levels of Hepatic Triglycerides

Cited by 334 publications

References 43 publications

Circadian regulation of lipid metabolism

Circadian regulation of lipid metabolism

Circadian control of oscillations in mitochondrial rate-limiting enzymes and nutrient utilization by PERIOD proteins

Rhythmic Oxygen Levels Reset Circadian Clocks through HIF1α

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