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

Meshail Okla, Jamal Omran Al Madani, Soonkyu Chung, Musaad Alfayez

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
Article number1900925
JournalMolecular Nutrition and Food Research
Volume64
Issue number1
DOIs
StatePublished - Jan 1 2020

Fingerprint

Apigenin
apigenin
interleukin-1
prostaglandin synthase
Cyclooxygenase 2
adipocytes
Interleukin-1
Dinoprostone
Adipocytes
prostaglandins
Interleukin-1beta
inflammation
obesity
Obesity
Prostaglandin Receptors
Inflammation
receptors
RNA Interference
anti-inflammatory activity
RNA interference

Keywords

  • apigenin
  • brown adipocytes
  • inflammation
  • interleukin-1β
  • uncoupling protein 1

ASJC Scopus subject areas

  • Biotechnology
  • Food Science

Cite this

Apigenin Reverses Interleukin-1β-Induced Suppression of Adipocyte Browning via COX2/PGE2 Signaling Pathway in Human Adipocytes. / Okla, Meshail; Al Madani, Jamal Omran; Chung, Soonkyu; Alfayez, Musaad.

In: Molecular Nutrition and Food Research, Vol. 64, No. 1, 1900925, 01.01.2020.

Research output: Contribution to journalArticle

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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.",
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