bims-ciryme 2022-02-20 papers

Sci Adv. 2022 Feb 18. 8(7): eabm1189

Muscle mitochondrial remodeling by intermittent glucocorticoid drugs requires an intact circadian clock and muscle PGC1α.

Mattia Quattrocelli, Michelle Wintzinger, Karen Miz, Daniel C Levine, Clara Bien Peek, Joseph Bass, Elizabeth M McNally.

Exogenous glucocorticoids interact with the circadian clock, but little attention is paid to the timing of intake. We recently found that intermittent once-weekly prednisone improved nutrient oxidation in dystrophic muscle. Here, we investigated whether dosage time affected prednisone effects on muscle bioenergetics. In mice treated with once-weekly prednisone, drug dosing in the light-phase promoted nicotinamide adenine dinucleotide (NAD+) levels and mitochondrial function in wild-type muscle, while this response was lost with dark-phase dosing. These effects depended on a normal circadian clock since they were disrupted in muscle from [Brain and muscle Arnt-like protein-1 (Bmal1)]-knockout mice. The light-phase prednisone pulse promoted BMAL1-dependent glucocorticoid receptor recruitment on noncanonical targets, including Nampt and Ppargc1a [peroxisome proliferator-activated receptor-γ coactivator 1α (PGC1α)]. In mice with muscle-restricted inducible PGC1α ablation, bioenergetic stimulation by light-phase prednisone required PGC1α. These results demonstrate that glucocorticoid "chronopharmacology" for muscle bioenergetics requires an intact clock and muscle PGC1α activity.

DOI: https://doi.org/10.1126/sciadv.abm1189

Metabolism. 2022 Feb 09. pii: S0026-0495(22)00036-1. [Epub ahead of print] 155158

Chronic circadian disruption on a high-fat diet impairs glucose tolerance.

Kirsi-Marja Zitting, Ramalingam Vetrivelan, Robin K Yuan, Nina Vujovic, Wei Wang, Sathyajit S Bandaru, Stuart F Quan, Elizabeth B Klerman, Frank A J L Scheer, Orfeu M Buxton, Jonathan S Williams, Jeanne F Duffy, Clifford B Saper, Charles A Czeisler.

BACKGROUND: Nearly 14% of Americans experience chronic circadian disruption due to shift work, increasing their risk of obesity, diabetes, and other cardiometabolic disorders. These disorders are also exacerbated by modern eating habits such as frequent snacking and consumption of high-fat foods.
METHODS: We investigated the effects of recurrent circadian disruption (RCD) on glucose metabolism in C57BL/6 mice and in human subjects exposed to non-24-h light-dark (LD) schedules vs. those on standard 24-h LD schedules. These LD schedules were designed to cause circadian misalignment between behaviors including rest/activity and fasting/feeding with the output of the near-24-h circadian system, while minimizing sleep loss, and were maintained for 12 weeks in mice and 3 weeks in humans. We examined interactions of these circadian-disrupted schedules compared to control 24-h schedules with a lower-fat diet (LFD, 13% in mouse and 25-27% in humans) and high-fat diet (HFD, 45% in mouse and 45-50% in humans). We also used young vs. old mice to determine whether they would respond differently to RCD.
RESULTS: When combined with a HFD, we found that RCD caused significant weight gain in mice and significantly impaired glucose tolerance and insulin sensitivity in both mice and humans, but this did not occur when RCD was combined with a LFD. This effect was similar in both young and older mice.
CONCLUSION: These results suggest that reducing dietary fat may protect against the metabolic consequences of a lifestyle (such as shift work) that involves chronic circadian disruption.

Keywords: Glucose tolerance; High-fat diet; Insulin sensitivity; Recurrent circadian disruption; Shift work; Weight gain

DOI: https://doi.org/10.1016/j.metabol.2022.155158

Elife. 2022 Feb 18. pii: e65419. [Epub ahead of print]11

Science Forum: Sex differences and sex bias in human circadian and sleep physiology research.

Manuel Spitschan, Nayantara Santhi, Amrita Ahluwalia, Dorothee Fischer, Lilian Hunt, Natasha Karp, Francis Lévi, Ines Pineda-Torra, Parisa Vidafar, Rhiannon White.

Growing evidence shows that sex differences impact many facets of human biology. Here we review and discuss the impact of sex on human circadian and sleep physiology, and we uncover a data gap in the field investigating the non-visual effects of light in humans. A virtual workshop on the biomedical implications of sex differences in sleep and circadian physiology then led to the following imperatives for future research: (1) design research to be inclusive and accessible, (2) implement recruitment strategies that lead to a sex-balanced sample, (3) use data visualization to grasp the effect of sex, (4) implement statistical analyses that include sex as a factor and/or perform group analyses by sex, where possible, (5) make participant-level data open and available to facilitate future meta-analytic efforts.

Keywords: human

DOI: https://doi.org/10.7554/eLife.65419