Clock genes regulate the feeding schedule-dependent diurnal rhythm changes in hexose transporter gene expressions through the binding of BMAL1 to the promoter/enhancer and transcribed regions

miRNA-10a is rhythmically expressed and regulates genes involved in lipid and glucose metabolism. However, the effects of miRNA-10a on obesity and glucose intolerance, as well as on the diurnal pattern of expression of circadian clock genes, remain unknown. We explored the effects of miRNA-10a-5p on insulin resistance and on the diurnal patterns of serum triglycerides and gut microbiota in high-fat diet- (HFD-) fed mice. The results showed that oral administration of miRNA-10a-5p significantly prevented body weight gain and improved glucose tolerance and insulin sensitivity in HFD-fed mice. Administration of miRNA-10a-5p also maintained the diurnal rhythm of Clock, Per2, and Cry1 expression, as well as serum glucose and triglyceride levels. Surprisingly, the diurnal oscillations of three genera of microbes, Oscillospira, Ruminococcus, and Lachnospiraceae, disrupted by HFD feeding, maintained by administration of miRNA-10a-5p. Moreover, a strong positive correlation was found between hepatic Clock expression and relative abundance of Lachnospiraceae, both in control mice (r=0.877) and in mice administered miRNA-10a-5p (r=0.853). Furthermore, we found that along with changes in Lachnospiraceae abundance, butyrate content in the feces maintained a diurnal rhythm after miRNA-10a-5p administration in HFD-fed mice. In conclusion, we suggest that miRNA-10a-5p may improve HFD-induced glucose intolerance and insulin resistance through the modulation of the diurnal rhythm of Lachnospiraceae and its metabolite butyrate. Therefore, miRNA-10a-5p may have preventative properties in subjects with metabolic disorders.

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Glucocorticoid receptor activation stimulates the sodium-chloride cotransporter and influences the diurnal rhythm of its phosphorylation

AJP Renal Physiology ◽

10.1152/ajprenal.00372.2019 ◽

2019 ◽

Vol 317 (6) ◽

pp. F1536-F1548 ◽

Cited By ~ 3

Author(s):

Jessica Ruth Ivy ◽

Natalie K. Jones ◽

Hannah M. Costello ◽

Morag K. Mansley ◽

Theresa S. Peltz ◽

...

Keyword(s):

Sodium Chloride ◽

Glucocorticoid Receptor ◽

Diurnal Rhythm ◽

Clock Genes ◽

Receptor Activation ◽

Plasma Corticosterone ◽

Sodium Balance ◽

Acute Administration ◽

Sodium Chloride Cotransporter ◽

Protein Pool

The sodium-chloride cotransporter (NCC) in the distal convoluted tubule contributes importantly to sodium balance and blood pressure (BP) regulation. NCC phosphorylation determines transport activity and has a diurnal rhythm influenced by glucocorticoids. Disturbing this rhythm induces “nondipping” BP, an abnormality that increases cardiovascular risk. The receptor through which glucocorticoids regulate NCC is not known. In this study, we found that acute administration of corticosterone to male C57BL6 mice doubled NCC phosphorylation without affecting total NCC abundance in both adrenalectomized and adrenal-intact mice. Corticosterone also increased the whole kidney expression of canonical clock genes: period circadian protein homolog 1 ( Per1), Per2, cryptochrome 1, and aryl hydrocarbon receptor nuclear translocator-like protein 1. In adrenal-intact mice, chronic blockade of glucocorticoid receptor (GR) with RU486 did not change total NCC but prevented corticosterone-induced NCC phosphorylation and activation of clock genes. Blockade of mineralocorticoid receptor (MR) with spironolactone reduced the total pool of NCC but did not affect stimulation by corticosterone. The diurnal rhythm of NCC phosphorylation, measured at 6-h intervals, was blunted by chronic GR blockade, and a similar dampening of diurnal variation was seen in GR heterozygous null mice. These effects on NCC phosphorylation did not reflect altered rhythmicity of plasma corticosterone or serum and glucocorticoid-induced kinase 1 activity. Both mineralocorticoids and glucocorticoids emerge as regulators of NCC, acting via distinct receptor pathways. MR activation provides maintenance of the NCC protein pool; GR activation dynamically regulates NCC phosphorylation and establishes the diurnal rhythm of NCC activity. This study has implications for circadian BP homeostasis, particularly in individuals with abnormal glucocorticoid signaling as is found in chronic stress and corticosteroid therapy.

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The HTR1 Gene Is a Dominant Negative Mutant Allele of MTH1 and Blocks Snf3- and Rgt2-Dependent Glucose Signaling in Yeast

Journal of Bacteriology ◽

10.1128/jb.182.2.540-542.2000 ◽

2000 ◽

Vol 182 (2) ◽

pp. 540-542 ◽

Cited By ~ 35

Author(s):

Frank Schulte ◽

Roman Wieczorke ◽

Cornelis P. Hollenberg ◽

Eckhard Boles

Keyword(s):

Gene Expression ◽

Mutant Allele ◽

Transcriptional Regulator ◽

Dominant Negative ◽

Dominant Negative Mutant ◽

Hexose Transporter ◽

Transporter Gene ◽

Glucose Signaling ◽

Mutant Forms ◽

Negative Mutant

ABSTRACT Saccharomyces cerevisiae HTR1 mutants are severely impaired in the uptake of glucose. We have cloned dominantHTR1 mutant alleles and show that they encode mutant forms of the Mth1 protein. Mth1 is shown to be involved in carbon source-dependent regulation of its own, invertase and hexose transporter gene expression. The mutant forms block the transduction of the Snf3- and Rgt2-mediated glucose signals upstream of the Rgt1 transcriptional regulator.

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Season-dependent differential effect of temperature on diurnal rhythm of expression of core clock genes in the pineal organ of an air-breathing catfish, Clarias gariepinus

Biological Rhythm Research ◽

10.1080/09291016.2018.1525139 ◽

2018 ◽

Vol 51 (1) ◽

pp. 120-138

Author(s):

Saurav Saha ◽

Kshetrimayum Manisana Singh ◽

Braj Bansh Prasad Gupta

Keyword(s):

Diurnal Rhythm ◽

Differential Effect ◽

Pineal Organ ◽

Clock Genes ◽

Clarias Gariepinus ◽

Effect Of Temperature ◽

Air Breathing

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Regulation of circadian gene expression in the kidney by light and food cues in rats

AJP Regulatory Integrative and Comparative Physiology ◽

10.1152/ajpregu.00578.2009 ◽

2010 ◽

Vol 298 (3) ◽

pp. R635-R641 ◽

Cited By ~ 23

Author(s):

Tao Wu ◽

Yinhua Ni ◽

Yue Dong ◽

Jiafeng Xu ◽

Xiaohong Song ◽

...

Keyword(s):

Gene Expression ◽

Circadian Rhythm ◽

Clock Genes ◽

Feeding Schedule ◽

Circadian Gene ◽

Food Cues ◽

Peripheral Clocks ◽

Synchronization Effect ◽

The Individual ◽

External Time

Although studies involving the circadian response to external time cues indicate that the peripheral clocks are dominated mainly by food cues, whether and how changes in the light and food cues affect the circadian rhythm of the renal clock is still largely unknown. In the present study, we found that the circadian phases of Bmal1, Clock, Cry1, Per1, and Per2 were altered differently by the stimuli of food and light cues in the kidney. After the individual reversal of the light-dark (LD) cycle for 7 days, Per1 displayed a 4-h phase delay, whereas the peak phases of Bmal1, Clock, Cry1 and Per2 almost remained the same as those in the control condition. With regard to the feeding-induced circadian resetting of the renal clock, we found that the resetting processes of clock genes could not be completed within 7 days, suggesting a weak synchronization effect of the food cue on the renal circadian clock. Moreover, the reentrainment of the clock genes was greatly enhanced after the reversal of both the feeding schedule and the LD cycle. Noticeably, the phases of Per1 and Clock were shifted most rapidly by 12 h within 3 days after the simultaneous reversal of the feeding schedule and the LD cycle, whereas their peak phases were only shifted by 4 h and 8 h, respectively, on the 7th day after the individual reversal of the feeding schedule. Thus Per1 and Clock may play important roles in the light-induced resetting of the circadian rhythms in the kidney.

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