Diego Sales de Oliveira1, Isabela Bruna Pires Borges1, Suely Kazue Nagahashi Marie2, Antonio Marcondes Lerario3, Sueli Mieko Oba-Shinjo2, Samuel Katsuyuki Shinjo1

1Division of Rheumatology, Laboratory of Inflammatory Myopathies, Faculdade de Medicina FMUSP, Universidade de Sao Paulo, Brazil
2Department of Neurology, Laboratory of Molecular and Cellular Biology, Faculdade de Medicina FMUSP, Universidade de Sao Paulo, Brazil
3Department of Internal Medicine, Division of Metabolism, Endocrinology and Diabetes, University of Michigan, Ann Arbor, MI, USA

Keywords: Exercise training, fat infiltration, insulin resistance, myopathies, myositis.


Objectives: This study aims to evaluate the effects of exercise training on intramuscular lipid content and genes related to insulin pathway in patients with systemic autoimmune myopathies (SAMs).

Patients and methods: Between January 2016 and May 2019, a total of seven patients with dermatomyositis (DM; 3 males, 4 females; mean age: 49.8±2.3 years; range, 43 to 54 years), six with immune mediated necrotizing myopathy (IMNM; 3 males, 3 females; mean age: 58.5±10.6 years; range, 46 to 74 years), and 10 control individuals (CTRL group; 4 males, 6 females; mean age: 48.7±3.9 years; range, 41 to 56 years) were included. The muscle biopsy before and after the intervention was performed to evaluate the intramuscular lipid content. Patients underwent a combined exercise training program for 12 weeks. Skeletal muscle gene expression was analyzed and the DM versus CTRL group, DM pre- and post-, and IMNM pre- and post-intervention were compared.

Results: The DM group had a higher intramuscular lipid content in type II muscle fibers compared to the CTRL group. After the intervention, there was a reduction of lipid content in type I and II fibers in DM and IMNM group. The CTRL group showed a significantly higher expression of genes related to insulin and lipid oxidation pathways (AMPKβ2, AS160, INSR, PGC1-α, PI3K, and RAB14) compared to the DM group. After exercise training, there was an increase gene expression related to insulin pathway and lipid oxidation in DM group (AMPKβ2, AS160, INSR, PGC1-α, PI3K, and RAB14) and in IMNM group (AKT2, AMPKβ2, RAB10, RAB14, and PGC1-α).

Conclusion: Exercise training attenuated the amount of fat in type I and II muscle fibers in patients with DM and IMNM and increased gene expression related to insulin pathways and lipid oxidation in DM and IMNM. These results suggest that exercise training can improve the quality and metabolic functions of skeletal muscle in these diseases.

Citation: de Oliveira DS, Borges IBP, Marie SKN, Lerario AM, Oba-Shinjo SM, Shinjo SK. Exercise training attenuates skeletal muscle fat infiltration and improves insulin pathway of patients with immune-mediated necrotizing myopathies and dermatomyositis. Arch Rheumatol 2023;38(2):189-199. doi: 10.46497/ArchRheumatol.2023.9257

Ethics Committee Approval

The study protocol was approved by the Registered at ClinicalTrials.gov and approved by the local ethics committee (CAAE number: 61474416.5.0000.0068). The study was conducted in accordance with the principles of the Declaration of Helsinki.

Author Contributions

Conception and design, drafting the article; final approval of the article: D.S.O., I.B.P.B., S.K.S.; Analysis and interpretation of data, revising and final approval of the article: S.K.N.M., A.M.L., S.M.O.S.

Conflict of Interest

The authors declared no conflicts of interest with respect to the authorship and/or publication of this article.

Financial Disclosure

This study was funded by the Fundação de Amparo à Pesquisa do Estado de São Paulo, São Paulo, Brazil (2016/19771-5 to D.S.O., 2019/11367-9 to I.B.P.B., and 2017/13109-1 to S.K.S.); Conselho Nacional de Desenvolvimento Científico e Tecnológico, São Paulo, Brazil (303379/2018-9 to S.K.S.); and Faculdade de Medicina da Universidade de São Paulo, São Paulo, Brazil (to S.M.O.-S., S.K.N.M., and S.K.S.).

Data Sharing Statement

The data that support the findings of this study are available from the corresponding author upon reasonable request.