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(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

Leucine Supplementation Decreases HDAC4 Expression and Nuclear Localization in Skeletal Muscle Fiber of Rats Submitted to Hindlimb Immobilization

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Author(s):
Alves, Paula K. N. [1] ; Cruz, Andre [1] ; Silva, William J. [1] ; Labeit, Siegfried [2, 3] ; Moriscot, Anselmo S. [1]
Total Authors: 5
Affiliation:
[1] Univ Sao Paulo, Inst Biomed Sci, Dept Anat, BR-05508000 Sao Paulo - Brazil
[2] Univ Med Mannheim, Fac Clin Med Mannheim, Inst Integrat Pathophysiol, Univ Heidelberg, D-68169 Mannheim - Germany
[3] Myomedix GmbH, D-69151 Neckargemund - Germany
Total Affiliations: 3
Document type: Journal article
Source: CELLS; v. 9, n. 12 DEC 2020.
Web of Science Citations: 0
Abstract

In this study we surveyed a rat skeletal muscle RNA-Seq for genes that are induced by hindlimb immobilization and, in turn, become attenuated by leucine supplementation. This approach, in search of leucine-atrophy protection mediating genes, identified histone deacetylase 4 (HDAC4) as highly responsive to both hindlimb immobilization and leucine supplementation. We then examined the impact of leucine on HDAC4 expression, tissue localization, and target genes. A total of 76 male Wistar rats (similar to 280 g) were submitted to hindlimb immobilization and/or leucine supplementation for 3, 7 and 12 days. These animals were euthanized, and soleus muscle was removed for further analysis. RNA-Seq analysis of hindlimb immobilized rats indicated a sharp induction (log2 = 3.4) of HDAC4 expression which was attenuated by leucine supplementation (similar to 50%). Real-time PCR and protein expression analysis by Western blot confirmed increased HDAC4 mRNA after 7 days of hindlimb immobilization and mitigation of induction by leucine supplementation. Regarding the HDAC4 localization, the proportion of positive nuclei was higher in the immobilized group and decreased after leucine supplementation. Also, we found a marked decrease of myogenin and MAFbx-atrogin-1 mRNA levels upon leucine supplementation, while CAMKII and DACH2 mRNA levels were increased by leucine supplementation. Our data suggest that HDAC4 inhibition might be involved in the anti-atrophic effects of leucine. (AU)

FAPESP's process: 15/04090-0 - Identification and caracterization of mechanisms involved in skeletal muscle mass control and regeneration
Grantee:Anselmo Sigari Moriscot
Support type: Research Projects - Thematic Grants
FAPESP's process: 18/24419-4 - Effect of leucine on the expression of miR-299A and HDAC4 in the skeletal muscle of rats submitted to immobilization: implications for the control of muscle mass
Grantee:Paula Ketilly Nascimento Alves
Support type: Scholarships in Brazil - Doctorate (Direct)
FAPESP's process: 17/09398-8 - Interplay betweeen myostatin and mTORC1 pathways in skeletal muscle: implications for a thyroid hormone biological action
Grantee:André Cruz de Oliveira
Support type: Scholarships in Brazil - Doctorate (Direct)