A Global Loss of Dio2 Leads to Unexpected Changes in Function and Fiber Types of Slow Skeletal Muscle in Male Mice
| Autor: | Marian J. Zuidwijk, Travis Petersen, Benjamin Sager, Warner S. Simonides, Rob Janssen, Amy J. Wagers, Cristina Luongo, Cecilia Martin, Alessandro Marsili, Monica Dentice, Adriana Roginski Guetter, Anita Boelen, P. Reed Larsen, Ashley N. Ogawa-Wong, J. Enrique Silva, Domenico Salvatore, Colleen Carmody, Neil M. Neumann, Ann Marie Zavacki, Elizabeth Y Wu, Kaman Hau, Sylvia Bogaards |
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| Přispěvatelé: | Physiology, ACS - Heart failure & arrhythmias, ACS - Pulmonary hypertension & thrombosis, Endocrinology Laboratory, AGEM - Endocrinology, metabolism and nutrition, Carmody, C., Ogawa-Wong, A. N., Martin, C., Luongo, C., Zuidwijk, M., Sager, B., Petersen, T., Roginski Guetter, A., Janssen, R., Wu, E. Y., Bogaards, S., Neumann, N. M., Hau, K., Marsili, A., Boelen, A., Silva, J. E., Dentice, M., Salvatore, Domenico, Wagers, A. J., Larsen, P. R., Simonides, W. S., Zavacki, A. M. |
| Rok vydání: | 2019 |
| Předmět: |
Male
0301 basic medicine medicine.medical_specialty Gene Expression DIO2 030209 endocrinology & metabolism Iodide Peroxidase Cell Line Myoblasts 03 medical and health sciences 0302 clinical medicine Endocrinology Internal medicine Precursor cell medicine Animals Myocyte Muscle Skeletal Research Articles Mice Knockout Soleus muscle Chemistry Myogenesis Skeletal muscle Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha Mice Inbred C57BL Thyroxine Muscle Fibers Slow-Twitch 030104 developmental biology medicine.anatomical_structure Triiodothyronine C2C12 Immunostaining Muscle Contraction |
| Zdroj: | Carmody, C, Ogawa-Wong, A N, Martin, C, Luongo, C, Zuidwijk, M, Sager, B, Petersen, T, Roginski Guetter, A, Janssen, R, Wu, E Y, Bogaards, S, Neumann, N M, Hau, K, Marsili, A, Boelen, A, Silva, J E, Dentice, M, Salvatore, D, Wagers, A J, Larsen, P R, Simonides, W S & Zavacki, A M 2019, ' A Global Loss of Dio2 Leads to Unexpected Changes in Function and Fiber Types of Slow Skeletal Muscle in Male Mice ', Endocrinology, vol. 160, no. 5, pp. 1205-1222 . https://doi.org/10.1210/en.2019-00088 Endocrinology, 160(5), 1205-1222. The Endocrine Society |
| ISSN: | 1945-7170 0013-7227 |
| Popis: | The type 2 iodothyronine-deiodinase (D2) enzyme converts T(4) to T(3), and mice deficient in this enzyme [D2 knockout (D2KO) mice] have decreased T(3) derived from T(4) in skeletal muscle despite normal circulating T(3) levels. Because slow skeletal muscle is particularly susceptible to changes in T(3) levels, we expected D2 inactivation to result in more pronounced slow-muscle characteristics in the soleus muscle, mirroring hypothyroidism. However, ex vivo studies of D2KO soleus revealed higher rates of twitch contraction and relaxation and reduced resistance to fatigue. Immunostaining of D2KO soleus showed that these properties were associated with changes in muscle fiber type composition, including a marked increase in the number of fast, glycolytic type IIB fibers. D2KO soleus muscle fibers had a larger cross-sectional area, and this correlated with increased myonuclear accretion in myotubes formed from D2KO skeletal muscle precursor cells differentiated in vitro. Consistent with our functional findings, D2KO soleus gene expression was markedly different from that in hypothyroid wild-type (WT) mice. Comparison of gene expression between euthyroid WT and D2KO mice indicated that PGC-1α, a T(3)-dependent regulator of slow muscle fiber type, was decreased by ∼50% in D2KO soleus. Disruption of Dio2 in the C2C12 myoblast cell line led to a significant decrease in PGC-1α expression and a faster muscle phenotype upon differentiation. These results indicate that D2 loss leads to significant changes in soleus contractile function and fiber type composition that are inconsistent with local hypothyroidism and suggest that reduced levels of PCG-1α may contribute to the observed phenotypical changes. |
| Databáze: | OpenAIRE |
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