Document Type
Article
Publication Title
American Journal of Physiology Regulatory Integrative and Comparative Physiology
Department
Biological Sciences
ISSN
15221490
Volume
321
Issue
3
DOI
10.1152/ajpregu.00052.2021
First Page
R413
Last Page
R428
Publication Date
8-25-2021
Abstract
Elephant seals experience natural periods of prolonged food deprivation while breeding, molting, and undergoing postnatal development. Prolonged food deprivation in elephant seals increases circulating glucocorticoids without inducing muscle atrophy, but the cellular mechanisms that allow elephant seals to cope with such conditions remain elusive. We generated a cellular model and conducted transcriptomic, metabolic, and morphological analyses to study how seal cells adapt to sustained glucocorticoid exposure. Seal muscle progenitor cells differentiate into contractile myotubes with a distinctive morphology, gene expression profile, and metabolic phenotype. Exposure to dexamethasone at three ascending concentrations for 48 h modulated the expression of six clusters of genes related to structural constituents of muscle and pathways associated with energy metabolism and cell survival. Knockdown of the glucocorticoid receptor (GR) and downstream expression analyses corroborated that GR mediates the observed effects. Dexamethasone also decreased cellular respiration, shifted the metabolic phenotype toward glycolysis, and induced mitochondrial fission and dissociation of mitochondria-endoplasmic reticulum (ER) interactions without decreasing cell viability. Knockdown of DNA damage-inducible transcript 4 (DDIT4), a GR target involved in the dissociation of mitochondria-ER membranes, recovered respiration and modulated antioxidant gene expression in myotubes treated with dexamethasone. These results show that adaptation to sustained glucocorticoid exposure in elephant seal myotubes involves a metabolic shift toward glycolysis, which is supported by alterations in mitochondrial morphology and a reduction in mitochondria-ER interactions, resulting in decreased respiration without compromising cell survival.
Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 International License.
Recommended Citation
Torres-Velarde, Julia María; Kolora, Sree Rohit Raj; Khudyakov, Jane I.; Crocker, Daniel E.; Sudmant, Peter H.; and Vázquez-Medina, José Pablo, "Elephant seal muscle cells adapt to sustained glucocorticoid exposure by shifting their metabolic phenotype" (2021). Pacific Faculty Work. 259.
https://scholarlycommons.pacific.edu/all-faculty/259
