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. In this study, we investigated impacts of apigenin (Apg), a natural flavonoid with anti-inflammatory properties, on IL-1β activation and adipocyte browning.

Apg protected cAMP-induced browning from IL-1β in primary human adipocytes as evidenced by increased expression of brown-specific markers, mitochondrial content, and respiratory function. Apg significantly repressed inflammatory markers and NF-κB activation induced by IL-1β in these adipocytes. Intriguingly, Apg profoundly induced cyclooxygenase 2 (COX2) and prostaglandin E2 (PGE2) gene expression in response to IL-1β treatment. Conversely, COX2 pharmacological inhibition or RNA silencing attenuated the positive effect of Apg on adipocyte browning in IL-1β treated cells. Additionally, blockage of PGE2 receptor 4 (EP4) attenuated Apg-mediated adipocyte browning. The effect of Apg on adipocyte browning in IL-1β-treated adipocytes was 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 COX2/PGE2 axis for UCP1 induction via EP4 activation. Our data unravel the novel therapeutic values of Apg for treating obesity via adipocyte browning stimulation. This article is protected by copyright. All rights reserved.