Journal
FOOD SCIENCE & NUTRITION
Volume 10, Issue 7, Pages 2360-2369Publisher
WILEY
DOI: 10.1002/fsn3.2844
Keywords
C-X-C motif chemokine ligand 1; epinephrine; exercise; Interleukin-6; nobiletin
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Funding
- JSPS KAKENHI [19H02906]
- Grants-in-Aid for Scientific Research [19H02906] Funding Source: KAKEN
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Exercise increases the secretion of IL-6, and nobiletin promotes the secretion of IL-6 during exercise. Previous studies have shown that nobiletin increases IL-6 levels in C2C12 cells and rat plasma, while this study further explores how nobiletin enhances the secretion of IL-6 and CXCL-1 through the PKA pathway in beta 2-adrenergic receptor signaling.
Exercise increases the muscular secretion of Interleukin-6 (IL-6), which is partially regulated by beta 2-adrenergic receptor signaling. Nobiletin is a polymethoxyflavone (PMF) found in citrus fruits that induces the secretion of IL-6 from C2C12 myotubes, but it remains unclear whether nobiletin promotes IL-6 secretion during exercise. The aim of this study was to clarify the effects of nobiletin on IL-6 secretion during exercise. Nobiletin and epinephrine were found to synergistically increase IL-6 secretion from differentiated C2C12 cells, which was suppressed by the inhibition of adenylyl cyclase (AC) or protein kinase A (PKA). Treadmill running for 60 min increased plasma levels of IL-6, epinephrine, and norepinephrine in rats. Nobiletin (5 mg/kg) orally administered 30 min before running increased plasma IL-6 levels further, although it did not increase plasma epinephrine and norepinephrine. In a similar manner to IL-6, nobiletin and epinephrine synergistically increased the secretion of C-X-C motif chemokine ligand 1 (CXCL-1) from C2C12 cells, or the increase in plasma CXCL-1 was enhanced by nobiletin after treadmill running of rats. Our results suggest that nobiletin promotes IL-6 and CXCL-1 secretion from skeletal muscle by synergistic enhancement of the PKA pathway in beta 2-adrenergic receptor signaling.
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