| First Author | Quattrocelli M | Year | 2022 |
| Journal | Sci Adv | Volume | 8 |
| Issue | 7 | Pages | eabm1189 |
| PubMed ID | 35179955 | Mgi Jnum | J:321691 |
| Mgi Id | MGI:6887119 | Doi | 10.1126/sciadv.abm1189 |
| Citation | Quattrocelli M, et al. (2022) Muscle mitochondrial remodeling by intermittent glucocorticoid drugs requires an intact circadian clock and muscle PGC1alpha. Sci Adv 8(7):eabm1189 |
| abstractText | 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-gamma coactivator 1alpha (PGC1alpha)]. In mice with muscle-restricted inducible PGC1alpha ablation, bioenergetic stimulation by light-phase prednisone required PGC1alpha. These results demonstrate that glucocorticoid "chronopharmacology" for muscle bioenergetics requires an intact clock and muscle PGC1alpha activity. |
