Abstract
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.
In primary human adipocytes, the natural plant flavonoid apigenin protects from the dysregulated adipocyte browning caused by interleukin‐1 beta. Apigenin rescues adipocyte browning by decreasing inflammation and increasing cyclooxygenase 2 and prostaglandin E2 production. Prostaglandin E2 in these adipocytes signal through EP4, which mediates the increase in cAMP signaling and adipocyte browning in interleukin‐1 beta‐treated adipocytes.