Azelaic Acid Induces Mitochondrial Biogenesis in Skeletal Muscle by Activation of Olfactory Receptor 544
Open accessAbstract
Mouse olfactory receptor 544 (Olfr544) is ectopically expressed in varied extra-nasal organs with tissue specific functions. Here, we investigated the functionality of Olfr544 in skeletal muscle cells and tissue. The expression of Olfr544 is confirmed by RT-PCR and qPCR in skeletal muscle cells and mouse skeletal muscle assessed by RT-PCR and qPCR. Olfr544 activation by its ligand, azelaic acid (AzA, 50 μM), induced mitochondrial biogenesis and autophagy in cultured skeletal myotubes by induction of cyclic adenosine monophosphate-response element binding protein (CREB)-peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α)-extracellular signal-regulated kinase-1/2 (ERK1/2) signaling axis. The silencing Olfr544 gene expression abrogated these effects of AzA in cultured myotubes. Similarly, in mice, the acute subcutaneous injection of AzA induced the CREB-PGC-1α-ERK1/2 pathways in mouse skeletal muscle, but these activations were negated in those of Olfr544 knockout mice. These demonstrate that the induction of mitochondrial biogenesis in skeletal muscle by AzA is Olfr544-dependent. Oral administration of AzA to high-fat-diet fed obese mice for 6 weeks increased mitochondrial DNA content in the skeletal muscle as well. Collectively, these findings demonstrate that Olfr544 activation by AzA regulates mitochondrial biogenesis in skeletal muscle. Intake of AzA or food containing AzA may help to improve skeletal muscle function.
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Azelaic acid stimulates mitochondrial biogenesis, mitochondrial contents, and autophagy in skeletal muscle tissues via activation of olfactory receptor 544 in HFD-induced obese C57BL/6J mice and C2C12 myotubes.
“Thach et al. reported that administration of azelaic acid stimulates mitochondrial biogenesis, mitochondrial contents, and autophagy in skeletal muscle tissues via activation of olfactory receptor 544 in HFD-induced obese C57BL/6J mice and C2C12 myotubes.”
From Nutraceuticals in the Prevention and Treatment of the Muscle Atrophy (2021) · cites this paper as [79]
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Chen, Y., Wang, L., Zhu, Z., Pan, B., & Bai, J. (2026) · Bioscience Biotechnology and Biochemistry · doi:10.1093/bbb/zbag127
Extra-nasal odorant receptors: molecular mechanisms and therapeutic implications
Thach, T. T. (2026) · Frontiers in Physiology · doi:10.3389/fphys.2026.1869917
Lv, S., Liu, J., Zhou, Y., Yang, R., Zhang, T., Deng, Y., Chen, Y., Lai, C., & Chen, Q. (2026) · iScience · doi:10.1016/j.isci.2026.117757
- Authors
- Thach, T. T., Wu, C., Hwang, K. Y., & Lee, S.-J.
- Affiliations
- Korea University (KR)
- Corresponding author
- Lee, Sung-Joon
- Venue
- Frontiers in Physiology
- Publisher
- Frontiers Media SA
- Published
- 2020-04-17
- Volume
- 11
- Pages
- 329-329
- ISSN
- 1664-042X (ISSN-L)
- PMC
- PMC7199515
- OpenAlex
- W3017108291
- Cited by
- 37
- References
- 65
- Citations by year
- 2026: 5 · 2025: 5 · 2024: 6 · 2023: 7 · 2022: 4 · 2021: 9 · 2020: 1
- FWCI
- 3.16
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Frontiers in Physiology (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- National Research Foundation of Korea
- Topics
- Health Sciences › Medicine › Physiology › Adipose Tissue and Metabolism
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Muscle Physiology and Disorders
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mitochondrial Function and Pathology
- Keywords
- azelaic acid, mitochondrial biogenesis, skeletal muscle, autophagy, CREB, PGC-1α, ERK signaling, skeletal muscle myotubes, mitochondrial DNA content, high-fat diet, obesity
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