bims-ciryme 2022-12-18 papers

Cell Rep. 2022 Dec 13. pii: S2211-1247(22)01674-6. [Epub ahead of print]41(11): 111786

Divergent remodeling of the skeletal muscle metabolome over 24 h between young, healthy men and older, metabolically compromised men.

Jan-Frieder Harmsen, Michel van Weeghel, Rex Parsons, Georges E Janssens, Jakob Wefers, Dirk van Moorsel, Jan Hansen, Joris Hoeks, Matthijs K C Hesselink, Riekelt H Houtkooper, Patrick Schrauwen.

24 h whole-body substrate metabolism and the circadian clock within skeletal muscle are both compromised upon metabolic disease in humans. Here, we assessed the 24 h muscle metabolome by serial muscle sampling performed under 24 h real-life conditions in young, healthy (YH) men versus older, metabolically compromised (OMC) men. We find that metabolites associated with the initial steps of glycolysis and hexosamine biosynthesis are higher in OMC men around the clock, whereas metabolites associated with glutamine-alpha-ketoglutarate, ketone, and redox metabolism are lower in OMC men. The night period shows the largest number of differently expressed metabolites. Both groups demonstrate 24 h rhythmicity in half of the metabolome, but rhythmic metabolites only partially overlap. Specific metabolites are only rhythmic in YH men (adenosine), phase shifted in OMC men (cis-aconitate, flavin adenine dinucleotide [FAD], and uridine diphosphate [UDP]), or have a reduced 24 h amplitude in OMC men (hydroxybutyrate and hippuric acid). Our data highlight the plasticity of the skeletal muscle metabolome over 24 h and large divergence across the metabolic health spectrum.

Keywords: CP: Metabolism; FAD; PGK1; adenosine; circadian rhythm; glycolysis; hexosamine; hydroxybutyrate; insulin resistance; metabolomics; misalignment

DOI: https://doi.org/10.1016/j.celrep.2022.111786

Sci Rep. 2022 Dec 13. 12(1): 21561

Glial Bmal1 role in mammalian retina daily changes.

Serena Riccitelli, Fabio Boi, Davide Lonardoni, Lidia Giantomasi, Olga Barca-Mayo, Davide De Pietri Tonelli, Silvia Bisti, Stefano Di Marco, Luca Berdondini.

Visual information processing in the retina requires the rhythmic expression of clock genes. The intrinsic retinal circadian clock is independent of the master clock located in the hypothalamic suprachiasmatic nucleus and emerges from retinal cells, including glia. Less clear is how glial oscillators influence the daily regulation of visual information processing in the mouse retina. Here, we demonstrate that the adult conditional deletion of the gene Bmal1 in GLAST-positive glial cells alters retinal physiology. Specifically, such deletion was sufficient to lower the amplitude of the electroretinogram b-wave recorded under light-adapted conditions. Furthermore, recordings from > 20,000 retinal ganglion cells (RGCs), the retina output, showed a non-uniform effect on RGCs activity in response to light across different cell types and over a 24-h period. Overall, our results suggest a new role of a glial circadian gene in adjusting mammalian retinal output throughout the night-day cycle.

DOI: https://doi.org/10.1038/s41598-022-25783-1

Obesity (Silver Spring). 2022 Dec 14.

Time-restricted eating did not alter insulin sensitivity or β-cell function in adults with obesity: A randomized pilot study.

Anne E Bantle, Kheng Joe Lau, Qi Wang, Samar Malaeb, Tasma Harindhanavudhi, Emily N C Manoogian, Satchidananda Panda, Douglas G Mashek, Lisa S Chow.

OBJECTIVE: Decreased insulin sensitivity and impairment of β-cell function predate and predict development of type 2 diabetes mellitus. Time-restricted eating (TRE) might have a benefit for these parameters. The objective of this pilot study was to investigate this possibility.
METHODS: Secondary analysis of a randomized controlled trial comparing 12 weeks of TRE (8-hour eating window) to unrestricted eating (non-TRE) was performed. Participants were adults with overweight or obesity and without diabetes. Two-hour oral glucose tolerance testing was performed at baseline and end-intervention. Glucose tolerance test-derived measures of insulin sensitivity, insulin secretion, and β-cell function were compared between groups.
RESULTS: Participants (17 women/3 men with mean [SD] age 45.5 [12.1] years and BMI 34.1 [7.5] kg/m2 ) with a prolonged eating window (15.4 [0.9] hours) were randomized to TRE (n = 11) or non-TRE (n = 9). The quantitative insulin sensitivity check index (QUICKI), Stumvoll index, Avignon index, insulinogenic index, insulin area under the curve/glucose area under the curve, and oral disposition index did not differ between the TRE and non-TRE groups at end-intervention.
CONCLUSIONS: In adults with overweight or obesity and without diabetes, TRE did not significantly alter insulin sensitivity, insulin secretion, or β-cell function over a 12-week intervention. Whether TRE is beneficial in adults with prediabetes or type 2 diabetes mellitus warrants further investigation.

DOI: https://doi.org/10.1002/oby.23620

Nutrients. 2022 Nov 26. pii: 5034. [Epub ahead of print]14(23):

High-Fat-Diet-Evoked Disruption of the Rat Dorsomedial Hypothalamic Clock Can Be Prevented by Restricted Nighttime Feeding.

Anna Magdalena Sanetra, Katarzyna Palus-Chramiec, Lukasz Chrobok, Jagoda Stanislawa Jeczmien-Lazur, Emilia Gawron, Jasmin Daniela Klich, Kamil Pradel, Marian Henryk Lewandowski.

Obesity is a growing health problem for modern society; therefore, it has become extremely important to study not only its negative implications but also its developmental mechanism. Its links to disrupted circadian rhythmicity are indisputable but are still not well studied on the cellular level. Circadian food intake and metabolism are controlled by a set of brain structures referred to as the food-entrainable oscillator, among which the dorsomedial hypothalamus (DMH) seems to be especially heavily affected by diet-induced obesity. In this study, we evaluated the effects of a short-term high-fat diet (HFD) on the physiology of the male rat DMH, with special attention to its day/night changes. Using immunofluorescence and electrophysiology we found that both cFos immunoreactivity and electrical activity rhythms become disrupted after as few as 4 weeks of HFD consumption, so before the onset of excessive weight gain. This indicates that the DMH impairment is a possible factor in obesity development. The DMH cellular activity under an HFD became increased during the non-active daytime, which coincides with a disrupted rhythm in food intake. In order to explore the relationship between them, a separate group of rats underwent time-restricted feeding with access to food only during the nighttime. Such an approach completely abolished the disruptive effects of the HFD on the DMH clock, confirming its dependence on the feeding schedule of the animal. The presented data highlight the importance of a temporally regulated feeding pattern on the physiology of the hypothalamic center for food intake and metabolism regulation, and propose time-restricted feeding as a possible prevention of the circadian dysregulation observed under an HFD.

Keywords: chronobiology; food-entrainable oscillator; metabolism; obesity; time-restricted feeding

DOI: https://doi.org/10.3390/nu14235034

Proc Natl Acad Sci U S A. 2022 Dec 20. 119(51): e2205301119

The spectral sensitivity of human circadian phase resetting and melatonin suppression to light changes dynamically with light duration.

Melissa A St Hilaire, María L Ámundadóttir, Shadab A Rahman, Shantha M W Rajaratnam, Melanie Rüger, George C Brainard, Charles A Czeisler, Marilyne Andersen, Joshua J Gooley, Steven W Lockley.

Human circadian, neuroendocrine, and neurobehavioral responses to light are mediated primarily by melanopsin-containing intrinsically-photosensitive retinal ganglion cells (ipRGCs) but they also receive input from visual photoreceptors. Relative photoreceptor contributions are irradiance- and duration-dependent but results for long-duration light exposures are limited. We constructed irradiance-response curves and action spectra for melatonin suppression and circadian resetting responses in participants exposed to 6.5-h monochromatic 420, 460, 480, 507, 555, or 620 nm light exposures initiated near the onset of nocturnal melatonin secretion. Melatonin suppression and phase resetting action spectra were best fit by a single-opsin template with lambdamax at 481 and 483 nm, respectively. Linear combinations of melanopsin (ipRGC), short-wavelength (S) cone, and combined long- and medium-wavelength (L+M) cone functions were also fit and compared. For melatonin suppression, lambdamax was 441 nm in the first quarter of the 6.5-h exposure with a second peak at 550 nm, suggesting strong initial S and L+M cone contribution. This contribution decayed over time; lambdamax was 485 nm in the final quarter of light exposure, consistent with a predominant melanopsin contribution. Similarly, for circadian resetting, lambdamax ranged from 445 nm (all three functions) to 487 nm (L+M-cone and melanopsin functions only), suggesting significant S-cone contribution, consistent with recent model findings that the first few minutes of a light exposure drive the majority of the phase resetting response. These findings suggest a possible initial strong cone contribution in driving melatonin suppression and phase resetting, followed by a dominant melanopsin contribution over longer duration light exposures.

Keywords: circadian phase resetting; circadian rhythms; light; melanopsin; melatonin suppression

DOI: https://doi.org/10.1073/pnas.2205301119