TY - JOUR
T1 - Apigenin Reverses Interleukin-1β-Induced Suppression of Adipocyte Browning via COX2/PGE2 Signaling Pathway in Human Adipocytes
AU - Okla, Meshail
AU - Al Madani, Jamal Omran
AU - Chung, Soonkyu
AU - Alfayez, Musaad
N1 - Funding Information:
The authors acknowledge the funding obtained from the Research and Development (R&D) Program (Research Pooling Initiative), Ministry of Education, Riyadh, Saudi Arabia, (RPI-KSU). The authors wish to acknowledge the Stem Cell Lab in the College of Medicine at King Saud University for providing access to their facility to perform the experiments for this study. Further, the authors wish to thank Waad Houssain Alkaf for her technical support.
Publisher Copyright:
© 2019 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
PY - 2020/1/1
Y1 - 2020/1/1
N2 - Scope: Inflammatory responses to obesity, including interleukin-1 beta (IL-1β) activation, downregulate mitochondrial function and interfere with adipocyte browning, an important component of energy expenditure. This study investigates the impact of apigenin (Apg), a natural flavonoid with anti-inflammatory properties, on adipocyte browning in the presence of IL-1β. Methods and results: Apg protects dibutyryl-cAMP-induced browning from IL-1β in primary human adipocytes, as evidenced by increased brown-specific markers, mitochondrial content, and oxygen consumption. Apg significantly represses inflammatory markers and NF-κB activation induced by IL-1β in these adipocytes. Intriguingly, Apg profoundly induces cyclooxygenase 2 (COX2) and prostaglandin E2 (PGE2) expression in response to IL-1β treatment. Conversely, COX2 pharmacological inhibition or RNA silencing attenuates the positive effect of Apg on adipocyte browning in IL-1β-treated cells. Additionally, blockage of PGE2 receptor 4 (EP4) attenuates Apg-mediated adipocyte browning. The effect of Apg on adipocyte browning in IL-1β-treated adipocytes is accompanied by an elevation in intracellular Ca2+, partly due to TRPV1/4 receptor activation. Conclusion: Apg plays a protective role against inflammation-induced suppression of adipocyte browning by dampening inflammation and activating the COX2/PGE2 axis for uncoupling protein 1 induction via EP4 activation. These data unravel the novel therapeutic values of Apg for treating obesity via adipocyte browning stimulation.
AB - Scope: Inflammatory responses to obesity, including interleukin-1 beta (IL-1β) activation, downregulate mitochondrial function and interfere with adipocyte browning, an important component of energy expenditure. This study investigates the impact of apigenin (Apg), a natural flavonoid with anti-inflammatory properties, on adipocyte browning in the presence of IL-1β. Methods and results: Apg protects dibutyryl-cAMP-induced browning from IL-1β in primary human adipocytes, as evidenced by increased brown-specific markers, mitochondrial content, and oxygen consumption. Apg significantly represses inflammatory markers and NF-κB activation induced by IL-1β in these adipocytes. Intriguingly, Apg profoundly induces cyclooxygenase 2 (COX2) and prostaglandin E2 (PGE2) expression in response to IL-1β treatment. Conversely, COX2 pharmacological inhibition or RNA silencing attenuates the positive effect of Apg on adipocyte browning in IL-1β-treated cells. Additionally, blockage of PGE2 receptor 4 (EP4) attenuates Apg-mediated adipocyte browning. The effect of Apg on adipocyte browning in IL-1β-treated adipocytes is accompanied by an elevation in intracellular Ca2+, partly due to TRPV1/4 receptor activation. Conclusion: Apg plays a protective role against inflammation-induced suppression of adipocyte browning by dampening inflammation and activating the COX2/PGE2 axis for uncoupling protein 1 induction via EP4 activation. These data unravel the novel therapeutic values of Apg for treating obesity via adipocyte browning stimulation.
KW - apigenin
KW - brown adipocytes
KW - inflammation
KW - interleukin-1β
KW - uncoupling protein 1
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U2 - 10.1002/mnfr.201900925
DO - 10.1002/mnfr.201900925
M3 - Article
C2 - 31785208
AN - SCOPUS:85076199099
SN - 1613-4125
VL - 64
JO - Die Nahrung
JF - Die Nahrung
IS - 1
M1 - 1900925
ER -