Azelaic Acid Induces Mitochondrial Biogenesis in Skeletal Muscle by Activation of Olfactory Receptor 544
Autor: | Trung Thanh Thach, Chunyan Wu, Kwang Yeon Hwang, Sung-Joon Lee |
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Rok vydání: | 2019 |
Předmět: |
0301 basic medicine
mitochondrial biogenesis Physiology 030209 endocrinology & metabolism CREB lcsh:Physiology olfactory receptor 544 03 medical and health sciences 0302 clinical medicine Physiology (medical) Coactivator medicine skeletal muscle Receptor Original Research biology lcsh:QP1-981 Chemistry Myogenesis Autophagy Skeletal muscle Cell biology 030104 developmental biology medicine.anatomical_structure Mitochondrial biogenesis azelaic acid Knockout mouse biology.protein myotube |
Zdroj: | Frontiers in Physiology Frontiers in Physiology, Vol 11 (2020) |
ISSN: | 1664-042X |
Popis: | 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. |
Databáze: | OpenAIRE |
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