Cell selectivity in succinate receptor SUCNR1/GPR91 signaling in skeletal muscle
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Cell selectivity in succinate receptor SUCNR1/GPR91 signaling in skeletal muscle. / Abdelmoez, Ahmed M.; Dmytriyeva, Oksana; Zurke, Yasemin Xiomara; Trauelsen, Mette; Marica, Alesandra A.; Savikj, Mladen; Smith, Jonathon A.B.; Monaco, Claudia; Schwartz, Thue W.; Krook, Anna; Pillon, Nicolas J.
In: American Journal of Physiology - Endocrinology and Metabolism, Vol. 324, No. 4, 2023, p. E289-E298.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - Cell selectivity in succinate receptor SUCNR1/GPR91 signaling in skeletal muscle
AU - Abdelmoez, Ahmed M.
AU - Dmytriyeva, Oksana
AU - Zurke, Yasemin Xiomara
AU - Trauelsen, Mette
AU - Marica, Alesandra A.
AU - Savikj, Mladen
AU - Smith, Jonathon A.B.
AU - Monaco, Claudia
AU - Schwartz, Thue W.
AU - Krook, Anna
AU - Pillon, Nicolas J.
PY - 2023
Y1 - 2023
N2 - Succinate is released by skeletal muscle during exercise and activates SUCNR1/GPR91. Signaling of SUCNR1 is involved in metabolite-sensing paracrine communication in skeletal muscle during exercise. However, the specific cell types responding to succinate and the directionality of communication are unclear. We aim to characterize the expression of SUCNR1 in human skeletal muscle. De novo analysis of transcriptomic datasets demonstrated that SUCNR1 mRNA is expressed in immune, adipose, and liver tissues, but scarce in skeletal muscle. In human tissues, SUCNR1 mRNA was associated with macrophage markers. Single-cell RNA sequencing and fluorescent RNAscope demonstrated that in human skeletal muscle, SUCNR1 mRNA is not expressed in muscle fibers but coincided with macrophage populations. Human M2-polarized macrophages exhibit high levels of SUCNR1 mRNA and stimulation with selective agonists of SUCNR1 triggered Gq- and Gi-coupled signaling. Primary human skeletal muscle cells were unresponsive to SUCNR1 agonists. In conclusion, SUCNR1 is not expressed in muscle cells and its role in the adaptive response of skeletal muscle to exercise is most likely mediated via paracrine mechanisms involving M2-like macrophages within the muscle.NEW & NOTEWORTHY Macrophages but not skeletal muscle cells respond to extracellular succinate via SUCNR1/GPR91.
AB - Succinate is released by skeletal muscle during exercise and activates SUCNR1/GPR91. Signaling of SUCNR1 is involved in metabolite-sensing paracrine communication in skeletal muscle during exercise. However, the specific cell types responding to succinate and the directionality of communication are unclear. We aim to characterize the expression of SUCNR1 in human skeletal muscle. De novo analysis of transcriptomic datasets demonstrated that SUCNR1 mRNA is expressed in immune, adipose, and liver tissues, but scarce in skeletal muscle. In human tissues, SUCNR1 mRNA was associated with macrophage markers. Single-cell RNA sequencing and fluorescent RNAscope demonstrated that in human skeletal muscle, SUCNR1 mRNA is not expressed in muscle fibers but coincided with macrophage populations. Human M2-polarized macrophages exhibit high levels of SUCNR1 mRNA and stimulation with selective agonists of SUCNR1 triggered Gq- and Gi-coupled signaling. Primary human skeletal muscle cells were unresponsive to SUCNR1 agonists. In conclusion, SUCNR1 is not expressed in muscle cells and its role in the adaptive response of skeletal muscle to exercise is most likely mediated via paracrine mechanisms involving M2-like macrophages within the muscle.NEW & NOTEWORTHY Macrophages but not skeletal muscle cells respond to extracellular succinate via SUCNR1/GPR91.
KW - GPR91
KW - macrophage
KW - skeletal muscle
KW - succinate
KW - SUCNR1
U2 - 10.1152/ajpendo.00009.2023
DO - 10.1152/ajpendo.00009.2023
M3 - Journal article
C2 - 36812387
AN - SCOPUS:85150751560
VL - 324
SP - E289-E298
JO - American Journal of Physiology - Endocrinology and Metabolism
JF - American Journal of Physiology - Endocrinology and Metabolism
SN - 0193-1849
IS - 4
ER -
ID: 342539320