Intracellular calcium and NF-kB regulate hypoxia-induced leptin, VEGF, IL-6 and adiponectin secretion in human adipocytes

Azizah Al-Anazi, Ranjit Parhar, Soad Saleh, Reem Al-Hijailan, Angela Inglis, Mansour Al-Jufan, Mohammed Bazzi, Sarwar Hashmi, Walter Conca, Kate Collison, Futwan Al-Mohanna

Research output: Contribution to journalArticlepeer-review

28 Scopus citations


Aims: Hypoxia-induced adipokine release has been attributed mainly to HIF-1α. Here we investigate the role of intracellular calcium and NF-kB in the hypoxia-dependent release of leptin, VEGF, IL-6 and the hypoxia-induced inhibition of adiponectin release in human adipocytes. Main methods: We used intracellular calcium imaging to compare calcium status in preadipocytes and in adipocytes. We subjected both cell types to hypoxic conditions and measured the release of adipokines induced by hypoxia in the presence and absence of HIF-1α inhibitor YC-1, NF-κB inhibitor SN50 and intracellular calcium chelator BAPTA-AM. Key findings: We demonstrate reduced intracellular calcium oscillations and increased oxidative stress as the cells transitioned from preadipocytes to adipocytes. We show that differentiation of preadipocytes to adipocytes is associated with distinct morphological changes in the mitochondria. We also show that hypoxia-induced secretion of leptin, VEGF, IL-6 and hypoxia-induced inhibition of adiponectin secretion are independent of HIF-1α expression. The hypoxia-induced leptin, VEGF and IL-6 release are [Ca++]i dependent whereas adiponectin is NF-kB dependent. Significance: Our work suggests a major role for [Ca++]i in preadipocyte differentiation to adipocytes and that changes in mitochondrial morphology in the adipocytes might underlie the reduced calcium oscillations observed in the adipocytes. It also demonstrates that multiple signaling pathways are associated with the hypoxia-induced adipokine secretion.
Original languageEnglish (US)
Pages (from-to)275-284
Number of pages10
JournalLife Sciences
StatePublished - Oct 12 2018
Externally publishedYes

Bibliographical note

KAUST Repository Item: Exported on 2022-06-09
Acknowledgements: We are thankful to Dr. Rachid Sougrat (KAUST) for performing TEM and Mr. Mohammed Halabi for technical assistance. Our gratitude to Ms. Camelia Touzinte and Mr. Melvin Velasco for editorial assistance and to Mr. John Schneider for technical assistance. The authors are indebted to the KFSHRC Research Centre Administration, Training and Education Office. The work was partially supported by King Abdulaziz City for Science and Technology grant number KACST 0968-12 and KFSHRC research funds. There are no conflicts of interest to declare.
This publication acknowledges KAUST support, but has no KAUST affiliated authors.


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