Apigenin Reverses Interleukin-1β-Induced Suppression of Adipocyte Browning via COX2/PGE2 Signaling Pathway in Human Adipocytes.

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. 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. 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. © 2019 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Citation

Meshail Okla, Jamal Omran Al Madani, Soonkyu Chung, Musaad Alfayez. Apigenin Reverses Interleukin-1β-Induced Suppression of Adipocyte Browning via COX2/PGE2 Signaling Pathway in Human Adipocytes. Molecular nutrition & food research. 2020 Jan;64(1):e1900925

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PMID: 31785208

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