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Citations to this article

Intermittent glucocorticoid treatment improves muscle metabolism via the PGC1α/Lipin1 axis in an aging-related sarcopenia model
Ashok D. Prabakaran, … , Brian N. Finck, Mattia Quattrocelli
Ashok D. Prabakaran, … , Brian N. Finck, Mattia Quattrocelli
Published May 3, 2024
Citation Information: J Clin Invest. 2024;134(11):e177427. https://doi.org/10.1172/JCI177427.
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Research Article Aging Muscle biology Article has an altmetric score of 18

Intermittent glucocorticoid treatment improves muscle metabolism via the PGC1α/Lipin1 axis in an aging-related sarcopenia model

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Abstract

Sarcopenia burdens the older population through loss of muscle energy and mass, yet treatments to functionally rescue both parameters are lacking. The glucocorticoid prednisone remodels muscle metabolism on the basis of frequency of intake, but its mechanisms in sarcopenia are unknown. We found that once-weekly intermittent prednisone administration rescued muscle quality in aged 24-month-old mice to a level comparable to that seen in young 4-month-old mice. We discovered an age- and sex-independent glucocorticoid receptor transactivation program in muscle encompassing peroxisome proliferator–activated receptor γ coactivator 1 α (PGC1α) and its cofactor Lipin1. Treatment coordinately improved mitochondrial abundance through isoform 1 and muscle mass through isoform 4 of the myocyte-specific PGC1α, which was required for the treatment-driven increase in carbon shuttling from glucose oxidation to amino acid biogenesis. We also probed myocyte-specific Lipin1 as a nonredundant factor coaxing PGC1α upregulation to the stimulation of both oxidative and anabolic effects. Our study unveils an aging-resistant druggable program in myocytes for the coordinated rescue of energy and mass in sarcopenia.

Authors

Ashok D. Prabakaran, Kevin McFarland, Karen Miz, Hima Bindu Durumutla, Kevin Piczer, Fadoua El Abdellaoui Soussi, Hannah Latimer, Cole Werbrich, Hyun-Jy Chung, N. Scott Blair, Douglas P. Millay, Andrew J. Morris, Brendan Prideaux, Brian N. Finck, Mattia Quattrocelli

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Total citations by year

Year: 2024 Total
Citations: 3 3
Citation information
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Citations to this article in year 2024 (3)

Title and authors Publication Year
Glucocorticoid chrono-pharmacology unveils novel targets for the cardiomyocyte-specific GR-KLF15 axis in cardiac glucose metabolism
Hima Bindu Durumutla, Fadoua Soussi, Olukunle Akinborewa, Hannah Latimer, Ashok Prabakaran, Kevin McFarland, Kevin Piczer, Cole Werbrich, Mukesh Jain, Saptarsi Haldar, Mattia Quattrocelli
JCI Insight 2024
Glucocorticoid chrono-pharmacology unveils novel targets for the cardiomyocyte-specific GR-KLF15 axis in cardiac glucose metabolism.
Durumutla HB, Prabakaran AD, Soussi FEA, Akinborewa O, Latimer H, McFarland K, Piczer K, Werbrich C, Jain MK, Haldar SM, Quattrocelli M
bioRxiv : the preprint server for biology 2024
The human glucocorticoid receptor variant rs6190 promotes blood cholesterol and atherosclerosis
Durumutla HB, Haller A, Noble G, Prabakaran AD, McFarland K, Latimer H, Akinborewa O, Namjou-Khales B, Hui DY, Quattrocelli M
bioRxiv 2024

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