Poster Topical Area: Obesity

Location: Hall D

Poster Board Number: 704

P23-077 - Apigenin Reverses Interleukin 1β-induced Suppression of Adipocyte Browning via COX2/PGE2 Signaling Pathways in Human Adipocytes

Sunday, Jun 10
8:00 AM – 6:00 PM

Inflammatory response to obesity and activation of interleukin-1 beta (IL-1β) affects mitochondrial function and interferes with white adipose tissue (WAT) browning. Apigenin (Apg), a natural flavonoid, widely distributed in plants such as celery, parsley and chamomile, is known to have anti-inflammatory and antioxidant properties. In this study, we first tested whether Apg antagonizes the inhibitory effect of IL-1β on WAT browning. We observed that Apg protects cAMP-induced browning in IL-1β treated adipocytes as the gene expression of UCP1, the signature of brown adipocytes, was induced by more than 200-fold compared with IL-1β-treated adipocytes. Next, we tested whether Apg attenuates IL-1β-induced browning inhibition by targeting inflammation. Apg significantly repressed the gene expression of pro-inflammatory cytokines and chemoattractant proteins induced by IL-1β. Although Apg attenuates inflammation, we observed a significant induction in the gene expression of cyclooxygenase 2 (COX2), the rate-limiting enzyme for prostaglandin biosynthesis, and microsomal prostaglandin E synthase-1 (mPGES-1) by 1.5-fold and 1.7-fold compared with IL-1β-treated adipocytes, respectively. Although prostaglandin E2 (PGE2) may act as a pro-inflammatory mediator, PGE2 can bind to different subtypes of EP receptors (EP 1-4) and activate different signaling pathways. As we observed a significant induction in COX2 and PGE2 with concomitant decrease in inflammatory cytokines and an increase in UCP1, we speculate that Apg induces UCP1 by shifting COX2 and PGE2 from being immune mediators to thermogenic inducers in adipocytes. Likely, this is due to the preferential activation of EP-cAMP-PKA signaling in response to PGE2 ligand binding and the corresponding transactivation of the transcription factor CREB. Collectively, we demonstrated, for the first time, that Apg plays a protective role against inflammation-induced WAT browning inhibition via dampening inflammatory signaling and activating COX2/PGE2 signaling toward cAMP and CREB activation leading to UCP1 induction. Therefore, our data unravel the novel therapeutic values of Apg for treating obesity via adaptive thermogenesis stimulation.




Funding Source:

Stem Cell Unit, Department of Anatomy, College of Medicine, King Saud University, Riyadh, Saudi Arabia

Meshail Okla

Assistant Professor
King Saud University
Riyadh, Ar Riyad, Saudi Arabia