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Apigenin Reverses Interleukin‐1β‐Induced Suppression of Adipocyte Browning via COX2/PGE2 Signaling Pathway in Human Adipocytes
Author(s) -
Okla Meshail,
Al Madani Jamal Omran,
Chung Soonkyu,
Alfayez Musaad
Publication year - 2020
Publication title -
molecular nutrition and food research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.495
H-Index - 131
eISSN - 1613-4133
pISSN - 1613-4125
DOI - 10.1002/mnfr.201900925
Subject(s) - adipocyte , browning , medicine , endocrinology , inflammation , apigenin , chemistry , biology , adipose tissue , biochemistry , flavonoid , antioxidant
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 Ca 2+ , 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.