Comparison of expression patterns of six canonical clock genes of follicular phase and luteal phase in Small-tailed Han sheep

Abstract. The circadian rhythm is a biological rhythm that is closely related to the rhythmic expression of a series of clock genes. Results from several studies have indicated that clock genes are associated with the estrous cycle in female animals. Until now, the relationship between estrus cycle transition and clock gene expression in reproductive-axis-related tissues has remained unknown in Small-tailed Han (STH) sheep. This study was conducted to analyze the expression patterns of six canonical clock genes (Clock, BMAL1, Per1, Per2, Cry1, and Cry2) in the follicle phase and luteal phase of STH sheep. We found that all six genes were expressed in the brain, cerebellum, hypothalamus, pituitary, ovary, uterus, and oviduct in follicle and luteal phases. The results indicated that Clock expression was significantly higher in the cerebellum, hypothalamus, and uterus of the luteal phase than that of the follicle phase, whereas BMAL1 expression was significantly higher in the hypothalamus of the luteal phase than that of the follicle phase. Per1 expression was significantly higher in the brain, cerebellum, hypothalamus, and pituitary of the luteal phase than that of the follicle phase, and Per2 expression was significantly higher in the hypothalamus, pituitary, and uterus of the luteal phase than that of the follicle phase. Cry1 expression was significantly higher in the brain, cerebellum, and hypothalamus of the luteal phase than that of the follicle phase, whereas Cry2 expression was significantly higher in the pituitary of the luteal phase than that of the follicle phase. The clock gene expression in all tissues was different between follicle and luteal phases, but all clock gene mRNA levels were found to exhibit higher expression among seven tissues in the luteal phase. Our results suggest that estrous cycles may be associated with clock gene expression in the STH sheep. This is the first study to systematically analyze the expression patterns of clock genes of different estrous cycle in ewes, which could form a basis for further studies to develop the relationship between clock genes and the estrous cycle.

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Diurnal Corticosterone Presence and Phase Modulate Clock Gene Expression in the Male Rat Prefrontal Cortex

Endocrinology ◽

10.1210/en.2015-1884 ◽

2016 ◽

Vol 157 (4) ◽

pp. 1522-1534 ◽

Cited By ~ 17

Author(s):

Elizabeth R. Woodruff ◽

Lauren E. Chun ◽

Laura R. Hinds ◽

Robert L. Spencer

Keyword(s):

Gene Expression ◽

Prefrontal Cortex ◽

Clock Gene ◽

Expression Patterns ◽

Time Of Day ◽

Male Rat ◽

Mrna Levels ◽

Diurnal Pattern ◽

Peripheral Tissues ◽

Clock Gene Expression

Abstract Mood disorders are associated with dysregulation of prefrontal cortex (PFC) function, circadian rhythms, and diurnal glucocorticoid (corticosterone [CORT]) circulation. Entrainment of clock gene expression in some peripheral tissues depends on CORT. In this study, we characterized over the course of the day the mRNA expression pattern of the core clock genes Per1, Per2, and Bmal1 in the male rat PFC and suprachiasmatic nucleus (SCN) under different diurnal CORT conditions. In experiment 1, rats were left adrenal-intact (sham) or were adrenalectomized (ADX) followed by 10 daily antiphasic (opposite time of day of the endogenous CORT peak) ip injections of either vehicle or 2.5 mg/kg CORT. In experiment 2, all rats received ADX surgery followed by 13 daily injections of vehicle or CORT either antiphasic or in-phase with the endogenous CORT peak. In sham rats clock gene mRNA levels displayed a diurnal pattern of expression in the PFC and the SCN, but the phase differed between the 2 structures. ADX substantially altered clock gene expression patterns in the PFC. This alteration was normalized by in-phase CORT treatment, whereas antiphasic CORT treatment appears to have eliminated a diurnal pattern (Per1 and Bmal1) or dampened/inverted its phase (Per2). There was very little effect of CORT condition on clock gene expression in the SCN. These experiments suggest that an important component of glucocorticoid circadian physiology entails CORT regulation of the molecular clock in the PFC. Consequently, they also point to a possible mechanism that contributes to PFC disrupted function in disorders associated with abnormal CORT circulation.

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Diversified regulation of circadian clock gene expression following whole genome duplication

10.1101/2020.03.22.002162 ◽

2020 ◽

Author(s):

Alexander C. West ◽

Marianne Iversen ◽

Even H. Jørgensen ◽

Simen R. Sandve ◽

David G. Hazlerigg ◽

...

Keyword(s):

Gene Expression ◽

Whole Genome Duplication ◽

Clock Gene ◽

Genome Duplication ◽

Clock Genes ◽

Expression Patterns ◽

Whole Genome ◽

Functional Diversification ◽

Clock Gene Expression ◽

Multiple Copies

AbstractAcross taxa, circadian control of physiology and behavior arises from cell-autonomous oscillations in gene expression, governed by a networks of so-called ‘clock genes’, collectively forming transcription-translation feedback loops. In modern vertebrates, these networks contain multiple copies of clock gene family members, which arose through whole genome duplication (WGD) events during evolutionary history. It remains unclear to what extent multiple copies of clock gene family members are functionally redundant or have allowed for functional diversification. We addressed this problem through an analysis of clock gene expression in the Atlantic salmon, a representative of the salmonids, a group which has undergone at least 4 rounds of WGD since the base of the vertebrate lineage, giving an unusually large complement of clock genes. By comparing expression patterns across multiple tissues, and during development, we present evidence for gene- and tissue-specific divergence in expression patterns, consistent with functional diversification of clock gene duplicates. In contrast to mammals, we found no evidence for coupling between cortisol and circadian gene expression, but cortisol mediated non-circadian regulated expression of a subset of clock genes in the salmon gill was evident. This regulation is linked to changes in gill function necessary for the transition from fresh- to sea-water in anadromous fish. Overall, this analysis emphasises the potential for a richly diversified clock gene network to serve a mixture of circadian and non-circadian functions in vertebrate groups with complex genomes.Author SummaryThe generation of daily (circadian) rhythms in behaviour and physiology depends on the activities of networks of so-called clock genes. In vertebrates, these have become highly complex due to a process known as whole genome duplication, which has occurred repeatedly during evolutionary history, giving rise to additional copies of key elements of the clock gene network. It remains unclear whether this results in functional redundancy, or whether it has permitted new roles for clock genes to emerge. Here, based on studies in the Atlantic salmon, a species with an unusually large complement of clock genes, we present evidence in favour of the latter scenario. We observe marked tissue-specific, and developmentally-dependent differences in the expression patterns of duplicated copies of key clock genes, and we identify a subset of clock genes whose expression is associated with the physiological preparation to migrate to sea, but is independent of circadian regulation. Associated with this, cortisol secretion is uncoupled from circadian organisation, contrasting with the situation in mammals. Our results indicate that whole genome duplication has permitted clock genes to diversify into non-circadian functions, and raise interesting questions about the ubiquity of mammal-like coupling between circadian and endocrine function.

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A genetic CLOCK variant associated with cluster headache causing increased mRNA levels

Cephalalgia ◽

10.1177/0333102417698709 ◽

2017 ◽

Vol 38 (3) ◽

pp. 496-502 ◽

Cited By ~ 19

Author(s):

Carmen Fourier ◽

Caroline Ran ◽

Margret Zinnegger ◽

Anne-Sofie Johansson ◽

Christina Sjöstrand ◽

...

Keyword(s):

Gene Expression ◽

Circadian Rhythm ◽

Cluster Headache ◽

Clock Gene ◽

Control Sample ◽

Mrna Levels ◽

Nucleotide Polymorphisms ◽

Primary Fibroblast ◽

Clock Gene Expression ◽

Diurnal Preference

Background Cluster headache is characterized by recurrent unilateral headache attacks of severe intensity. One of the main features in a majority of patients is a striking rhythmicity of attacks. The CLOCK ( Circadian Locomotor Output Cycles Kaput) gene encodes a transcription factor that serves as a basic driving force for circadian rhythm in humans and is therefore particularly interesting as a candidate gene for cluster headache. Methods We performed an association study on a large Swedish cluster headache case-control sample (449 patients and 677 controls) screening for three single nucleotide polymorphisms (SNPs) in the CLOCK gene implicated in diurnal preference (rs1801260) or sleep duration (rs11932595 and rs12649507), respectively. We further wanted to investigate the effect of identified associated SNPs on CLOCK gene expression. Results We found a significant association with rs12649507 and cluster headache ( p = 0.0069) and this data was strengthened when stratifying for reported diurnal rhythmicity of attacks ( p = 0.0009). We investigated the effect of rs12649507 on CLOCK gene expression in human primary fibroblast cultures and identified a significant increase in CLOCK mRNA expression ( p = 0.0232). Conclusions Our results strengthen the hypothesis of the involvement of circadian rhythm in cluster headache.

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GDF-9 and BMP-15 mRNA Levels in Canine Cumulus Cells Related to Cumulus Expansion and the Maturation Process

Animals ◽

10.3390/ani10030462 ◽

2020 ◽

Vol 10 (3) ◽

pp. 462 ◽

Cited By ~ 3

Author(s):

George Ramirez ◽

Jaime Palomino ◽

Karla Aspee ◽

Monica De los Reyes

Keyword(s):

Gene Expression ◽

Estrous Cycle ◽

Expression Patterns ◽

Cumulus Cells ◽

Mrna Levels ◽

Cumulus Expansion ◽

Polymerase Chain ◽

Specific Regulation ◽

Reproductive Phases

The competence to undergo expansion is a characteristic of cumulus cells (CCs). The aim was to investigate the expression of GDF-9 and BMP-15 mRNA in canine cumulus cells in relation to cumulus expansion and meiotic development over the estrous cycle. CCs were recovered from nonmatured and in vitro-matured (IVM) dog cumulus oocyte complexes (COCs), which were obtained from antral follicles at different phases of the estrous cycle. Quantitative real-time polymerase chain reaction (q-PCR) was used to evaluate the relative abundance of GDF-9 and BMP-15 transcripts from the CCs with or without signs of expansion. The results were evaluated by ANOVA and logistic regression. The maturity of the oocyte and the expansion process affected the mRNA levels in CCs. There were differences (p < 0.05) in GDF-9 and BMP-15 gene expression in CCs isolated from nonmatured COCs when comparing the reproductive phases. Lower mRNA levels (p < 0.05) were observed in anestrus and proestrus in comparison to those in estrus and diestrus. In contrast, when comparing GDF-9 mRNA levels in IVM COCs, no differences were found among the phases of the estrous cycle in expanded and nonexpanded CCs (p < 0.05). However, the highest (p < 0.05) BMP-15 gene expression in CCs that did not undergo expansion was exhibited in anestrus and the lowest (p < 0.05) expression was observed in estrus in expanded CCs. Although the stage of the estrous cycle did not affect the second metaphase (MII )rates, the expanded CCs obtained at estrus coexisted with higher percentages of MII (p < 0.05). In conclusion, the differential expression patterns of GDF-9 and BMP-15 mRNA transcripts might be related to cumulus expansion and maturation processes, suggesting specific regulation and temporal changes in their expression.

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Clock gene expression is altered in veterans with sleep apnea

Physiological Genomics ◽

10.1152/physiolgenomics.00091.2018 ◽

2019 ◽

Vol 51 (3) ◽

pp. 77-82 ◽

Cited By ~ 6

Author(s):

Muna T. Canales ◽

Meaghan Holzworth ◽

Shahab Bozorgmehri ◽

Areef Ishani ◽

I. David Weiner ◽

...

Keyword(s):

Gene Expression ◽

Sleep Apnea ◽

Clock Gene ◽

Clock Genes ◽

Apnea Hypopnea Index ◽

Blood Collection ◽

Cross Sectional ◽

Sleep Complaints ◽

Clock Gene Expression ◽

Metabolic Outcomes

Clock gene dysregulation has been shown to underlie various sleep disorders and may lead to negative cardio-metabolic outcomes. However, the association between sleep apnea (SA) and core clock gene expression is unclear. We performed a cross-sectional analysis of 49 Veterans enrolled in a study of SA outcomes in veterans with chronic kidney disease, not selected for SA or sleep complaints. All participants underwent full polysomnography and next morning whole blood collection for clock gene expression. We defined SA as an apnea-hypopnea index ≥15 events/h; nocturnal hypoxemia(NH) was defined as ≥10% of total sleep time spent at <90% oxygen saturation. We used quantitative real-time PCR to compare the relative gene expression of clock genes between those with and without SA or NH. Clock genes studied were Bmal1, Ck1δ, Ck1ε, Clock, Cry1, Cry2, NPAS2, Per1, Per2, Per3, Rev-Erb-α, RORα, and Timeless. Our cohort was 90% male, mean age was 71 yr (SD 11), mean body mass index was 30 kg/m2 (SD 5); 41% had SA, and 27% had NH. Compared with those without SA, Per3 expression was reduced by 35% in SA ( P = 0.027). Compared with those without NH, NPAS2, Per1, and Rev-Erb-α expression was reduced in NH (50.4%, P = 0.027; 28.7%, P = 0.014; 31%, P = 0.040, respectively). There was no statistical difference in expression of the remaining clock genes by SA or NH status. Our findings suggest that SA or related NH and clock gene expression may be interrelated. Future study of 24 h clock gene expression in SA is needed to establish the role of clock gene regulation on the pathway between SA and cardio-metabolic outcomes.

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Clock Gene Expression in the Submandibular Glands

Journal of Dental Research ◽

10.1177/154405910508401219 ◽

2005 ◽

Vol 84 (12) ◽

pp. 1193-1197 ◽

Cited By ~ 20

Author(s):

M. Furukawa ◽

T. Kawamoto ◽

M. Noshiro ◽

K.K. Honda ◽

M. Sakai ◽

...

Keyword(s):

Salivary Gland ◽

Salivary Glands ◽

Clock Gene ◽

Clock Genes ◽

Expression Profiles ◽

Mrna Levels ◽

Peripheral Tissues ◽

Submandibular Glands ◽

Circadian Expression ◽

Clock Gene Expression

Clock genes, which mediate molecular circadian rhythms, are expressed in a circadian fashion in the suprachiasmatic nucleus and in various peripheral tissues. To establish a molecular basis for circadian regulation in the salivary glands, we examined expression profiles of clock-related genes and salivary gland-characteristic genes. Clock-related genes—including Per1, Per2, Cry1, Bmal1, Dec1, Dec2, Dbp, and Reverbα—showed robust circadian expression rhythms in the submandibular glands in 12:12-hour light-dark conditions. In addition, a robust circadian rhythm was observed in amylase 1 mRNA levels, whereas the expression of other salivary-gland-characteristic genes examined was not rhythmic. The Clock mutation resulted in increased or decreased mRNA levels of Per2, Bmal1, Dec1, Dec2, and Dbp, and in Cry1− /− background, Cry2 disruption also increased or decreased mRNA levels of these clock-related genes and the amylase 1 gene. These findings indicate that the Clock- and Cry-dependent molecular clock system is active in the salivary glands.

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P144 Clock gene expression levels inversely correlate with disease activity in ulcerative colitis and Crohn’s disease

Journal of Crohn s and Colitis ◽

10.1093/ecco-jcc/jjab076.271 ◽

2021 ◽

Vol 15 (Supplement_1) ◽

pp. S228-S228

Author(s):

Y Weintraub ◽

S Cohen ◽

N Chapnik ◽

A Anafy ◽

A Yerushalmy-Feler ◽

...

Keyword(s):

Gene Expression ◽

Ulcerative Colitis ◽

Crohn’S Disease ◽

Disease Activity ◽

Clock Gene ◽

Clock Genes ◽

Clinical Status ◽

Expression Levels ◽

Clock Gene Expression ◽

Gene Expression Levels

Abstract Background Pathophysiological mechanisms active in inflammatory bowel disease (IBD), such as mucosal barrier repair, innate and adaptive immune responses, intestinal motility and gut microbiome, all exhibit diurnal variations. Chronic disruption of the molecular clock augment inflammatory response. We have shown that newly diagnosed, naïve to treatment, young IBD patients showed reduced clock gene expression in both inflamed and non-inflamed intestinal tissues and in peripheral White Blood Cells (WBC). This reduction correlated with disease activity. Our aim in this study was to determine whether certain clock genes correlate with disease activity scores or inflammatory markers in Crohn’s disease (CD) vs. ulcerative colitis (UC). Methods 17 patients with CD and 13 with UC, 8–22 years old, were recruited. Patients were evaluated upon diagnosis and during medical treatment. Disease activity scores, C-reactive protein (CRP) and fecal calprotectin (Fcal) levels were measured and WBC were analysed for clock gene (CLOCK, BMAL1, CRY1, CRY2, PER1 and PER2) expression. Clock gene expression levels were correlated to disease activity scores (clinically active vs. remission), CRP levels (<5 mg/l vs. >5 mg/l) and Fcal levels (< 250 μg/mg vs. >250 μg/mg) in CD (21 samples) and UC (20 samples). Results In UC, BMAL (p<0.008), CLOCK (p<0.02), CRY1 (p<0.002), CRY2 (p<0.0009), PER1 (p<0.003) and PER2 (p<0.003) showed decreased expression when Fcal levels were > 250 μg/mg. When compared with the clinical status and CRP levels, only BMAL1 showed reduced expression (p<0.003 and p<0.001, respectively). In CD, clinical status correlated with clock gene expression: CLOCK (p<0.035), PER1 (p<0.001) and CRY1 (p<0.028) were reduced in active disease. CRP and Fcal did not correlate with clock gene expression. Conclusion Altered levels of certain clock genes were demonstrated in young CD and UC patients in exacerbation vs. remission. In UC, Fcal levels inversely correlated with all major circadian genes and partially with clinical status and CRP levels. In CD patients clock gene expression inversely correlated with clinical status.

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Differential Expression of Circadian Clock Genes in the Bovine Neuroendocrine Adrenal System

Journal of the Endocrine Society ◽

10.1210/jendso/bvab048.134 ◽

2021 ◽

Vol 5 (Supplement_1) ◽

pp. A66-A67

Author(s):

Audrey L Earnhardt ◽

David G Riley ◽

Noushin Ghaffari ◽

Penny K Riggs ◽

Charles R Long ◽

...

Keyword(s):

Gene Expression ◽

Circadian Clock ◽

Clock Gene ◽

Target Genes ◽

Clock Genes ◽

Expression Profiles ◽

Primary Objective ◽

Clock Gene Expression ◽

Adrenal System ◽

Circadian Clock Genes

Abstract The primary objective of this investigation was to determine whether circadian clock genes were differentially expressed within or among bovine hypothalamic paraventricular nucleus (PVN), anterior pituitary gland (AP), adrenocortical (AC) and adrenomedullary (AM) tissues. The PVN, AP, AC, and AM were isolated from 5-yr-old Brahman cows (n = 8) harvested humanely at an abattoir between 0800-1100 h. Expression of target genes in each sample was evaluated via RNA-sequencing analyses. Gene counts were normalized using the trimmed mean of M values (TMM) method in the edgeR Package from Bioconductor, R. The normalized gene counts of genes important for circadian rhythm were statistically analyzed using the GLM Procedure of SAS. The genes analyzed were circadian locomotor output cycles protein kaput (CLOCK), cryptochrome circadian regulator 1 and 2 (CRY1 and CRY2), aryl hydrocarbon receptor nuclear translocator like (ARNTL), period circadian regulator 1 and 2 (PER1 and PER2), neuronal PAS domain protein 2 (NPAS2), and nuclear receptor subfamily 1 group D member 1 (NR1D1). Overall, relative expression profiles of clock genes differed (P < 0.01) within each tissue with PER1 having greater expression in all tissues (P < 0.01). Within the PVN expression of CLOCK, CRY1, ARNTL, and PER2 was less than that of CRY2, NPAS2, and NR1D1 (P < 0.01). In the AP, with the exception of PER1, no other clock gene differed in degree of expression. In the AC, expression of CLOCK and NPAS2 was greater than CRY1, ARNTL, PER2, and NR1D1 (P < 0.05), whereas CRY2 expression exceeded only CRY1 (P < 0.05). Within the AM, CLOCK and CRY2 expression was greater than CRY1 and ARNTL (P < 0.05). Overall, clock gene expression among tissues differed (P < 0.01) for each individual clock gene. The AC and AM had similar clock gene expression, except expression of CRY2 and PER2 was greater in AM (P < 0.05). The AC and AM had greater expression of CLOCK than the PVN and AP (P < 0.01), with PVN having greater expression than AP (P < 0.01). The AP had greater expression of NPAS2, followed by PVN, with the least expression in the AC and AM (P < 0.01). Both PVN and AP had greater CRY1 and NR1D1 expression than AC or AM (P < 0.01). The AP had greater PER1 expression than PVN, AC, and AM (P < 0.01), whereas PVN, AC, and AM had greater ARNTL expression than AP (P < 0.05). Both AP and AM had greater expression of PER2 than PVN or AC (P < 0.01). The PVN had greater expression of CRY2 than the AP, AC, and AM (P < 0.01). These results indicated that within each tissue the various clock genes were expressed in different quantities. Also, the clock genes were expressed differentially among the tissues of the bovine neuroendocrine adrenal system. Temporal relationships of these genes with the primary endocrine products of these tissues should be investigated to define the roles of peripheral clock genes in regulation of metabolism and health.

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Rhythms during the polar night: evidence of clock-gene oscillations in the Arctic scallop Chlamys islandica

Proceedings of The Royal Society B Biological Sciences ◽

10.1098/rspb.2020.1001 ◽

2020 ◽

Vol 287 (1933) ◽

pp. 20201001

Author(s):

Mickael Perrigault ◽

Hector Andrade ◽

Laure Bellec ◽

Carl Ballantine ◽

Lionel Camus ◽

...

Keyword(s):

Gene Expression ◽

Clock Gene ◽

Clock Genes ◽

Biological Rhythms ◽

The Arctic ◽

Polar Night ◽

Clock Gene Expression ◽

Chlamys Islandica ◽

Autumnal Equinox ◽

Cyclic Variations

Arctic regions are highly impacted by climate change and are characterized by drastic seasonal changes in light intensity and duration with extended periods of permanent light or darkness. Organisms use cyclic variations in light to synchronize daily and seasonal biological rhythms to anticipate cyclic variations in the environment, to control phenology and to maintain fitness. In this study, we investigated the diel biological rhythms of the Arctic scallop, Chlamys islandica , during the autumnal equinox and polar night. Putative circadian clock genes and putative light perception genes were identified in the Arctic scallop. Clock gene expression oscillated in the three tissues studied (gills, muscle, mantle edge). The oscillation of some genes in some tissues shifted from daily to tidal periodicity between the equinox and polar night periods and was associated with valve behaviour. These results are the first evidence of the persistence of clock gene expression oscillations during the polar night and might suggest that functional clockwork could entrain rhythmic behaviours in polar environments.

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Influence of obesity, weight loss, and free fatty acids on skeletal muscle clock gene expression

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.00289.2019 ◽

2020 ◽

Vol 318 (1) ◽

pp. E1-E10 ◽

Cited By ~ 3

Author(s):

Laura Sardon Puig ◽

Nicolas J. Pillon ◽

Erik Näslund ◽

Anna Krook ◽

Juleen R. Zierath

Keyword(s):

Gene Expression ◽

Skeletal Muscle ◽

Weight Loss ◽

Circadian Clock ◽

Clock Gene ◽

Clock Genes ◽

Expression Profiles ◽

Normal Weight ◽

Nonesterified Fatty Acid ◽

Clock Gene Expression

The molecular circadian clock plays a role in metabolic homeostasis. We tested the hypothesis obesity and systemic factors associated with insulin resistance affect skeletal muscle clock gene expression. We determined clock gene expression in skeletal muscle of obese women ( n = 5) and men ( n = 18) before and 6 mo after Roux-en-Y gastric bypass (RYGB) surgery and normal-weight controls (women n = 6, men n = 8). Skeletal muscle clock gene expression was affected by obesity and weight loss. CRY1 mRNA ( P = 0.05) was increased and DBP mRNA ( P < 0.05) was decreased in obese vs. normal weight women and restored to control levels after RYGB-induced weight loss. CLOCK, CRY1, CRY2, and DBP mRNA ( P < 0.05) was decreased in obese men compared with normal weight men. Expression of all other clock genes was unaltered by obesity or weight loss in both cohorts. We correlated clock gene expression with clinical characteristics of the participants. Among the genes studied, DBP and PER3 expression was inversely correlated with plasma lipids in both cohorts. Circadian time-course studies revealed that core clock genes oscillate over time ( P < 0.05), with BMAL1, CIART, CRY2, DBP, PER1, and PER3 expression profiles altered by palmitate treatment. In conclusion, skeletal muscle clock gene expression and function is altered by obesity, coincident with changes in plasma lipid levels. Palmitate exposure disrupts clock gene expression in myotubes, indicating that dyslipidemia directly alters the circadian program. Strategies to reduce lipid overload and prevent elevations in nonesterified fatty acid and cholesterol levels may sustain circadian clock signals in skeletal muscle.

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