Research Paper Volume 13, Issue 18 pp 21962—21974
Dulaglutide improves muscle function by attenuating inflammation through OPA-1-TLR-9 signaling in aged mice
- 1 College of Pharmacy and Gachon Institute of Pharmaceutical Science, Gachon University, Incheon, Korea
- 2 Lee Gil Ya Cancer and Diabetes Institute, Gachon University, Incheon, Korea
- 3 Department of Internal Medicine, Gil Medical Center, Gachon University College of Medicine, Incheon, Korea
- 4 Gachon Medical and Convergence Institute, Gil Medical Center, Incheon, Korea
- 5 Department of Marine Bio and Medical Science, Hanseo University, Seosan, Korea
Received: June 23, 2021 Accepted: September 7, 2021 Published: September 19, 2021https://doi.org/10.18632/aging.203546
How to Cite
Copyright: © 2021 Khin et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Dulaglutide, a glucagon-like peptide-1 receptor (GLP-1R) agonist, is widely used to treat diabetes. However, its effects on muscle wasting due to aging are poorly understood. In the current study, we investigated the therapeutic potential and underlying mechanism of dulaglutide in muscle wasting in aged mice. Dulaglutide improved muscle mass and strength in aged mice. Histological analysis revealed that the cross-sectional area of the tibialis anterior (TA) in the dulaglutide-treated group was thicker than that in the vehicle group. Moreover, dulaglutide increased the shift toward middle and large-sized fibers in both young and aged mice compared to the vehicle. Dulaglutide increased myofiber type I and type IIa in young (18.5% and 8.2%) and aged (1.8% and 19.7%) mice, respectively, compared to the vehicle group. Peroxisome proliferator-activated receptor-gamma coactivator-1α (PGC-1α), a master regulator of mitochondrial biogenesis, decreased but increased by dulaglutide in aged mice. The expression of atrophic factors such as myostatin, atrogin-1, and muscle RING-finger protein-1 was decreased in aged mice, whereas that of the myogenic factor, MyoD, was increased in both young and aged mice following dulaglutide treatment. In aged mice, optic atrophy-1 (OPA-1) protein was decreased, whereas Toll-like receptor-9 (TLR-9) and its targeting inflammatory cytokines (interleukin-6 [IL-6] and tumor necrosis factor-α [TNF-α]) were elevated in the TA and quadriceps (QD) muscles. In contrast, dulaglutide administration reversed this expression pattern, thereby significantly attenuating the expression of inflammatory cytokines in aged mice. These data suggest that dulaglutide may exert beneficial effects in the treatment of muscle wasting due to aging.