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Biochem Biophys Res Commun. 2015 May 29;461(2):287-92. doi: 10.1016/j.bbrc.2015.04.020. Epub 2015 Apr 14.

Hypoxia potentiates tumor necrosis factor-α induced expression of inducible nitric oxide synthase and cyclooxygenase-2 in white and brown adipocytes.

Author information

1
Department of Internal Medicine, University Hospital of Zurich, Switzerland; Center of Competence Multimorbidity and University Research Priority Program "Dynamics of Healthy Aging", University of Zurich, Switzerland. Electronic address: Indranil.bhattacharya@usz.ch.
2
Department of Internal Medicine, University Hospital of Zurich, Switzerland.
3
Department of Internal Medicine, University Hospital of Zurich, Switzerland; Center of Competence Multimorbidity and University Research Priority Program "Dynamics of Healthy Aging", University of Zurich, Switzerland.
4
Department of Internal Medicine, University Hospital of Zurich, Switzerland; Center of Competence Multimorbidity and University Research Priority Program "Dynamics of Healthy Aging", University of Zurich, Switzerland; Zurich Center for Integrative Human Physiology, CH-8057, Zürich, Switzerland.

Abstract

Obesity involves hypoxic adipose tissue and low-grade chronic inflammation. We investigated the impact of hypoxia on inflammatory response to TNF-α in white and brown adipocytes. In response to TNF-α, the expression of the inducible enzymes iNOS and COX-2 was prominently and selectively potentiated during hypoxia while only moderately under normoxia. Levels of their products, nitrite and prostaglandinE2 were elevated accordingly. NS398, a selective COX-2 inhibitor, reduced nitrite levels. The expression of PGC-1α, a transcriptional co-activator involved in mitochondrial biogenesis, and PPARγ, a transcription factor involved in adipocyte homeostasis, was reduced by TNF-α during hypoxia. These results suggest that hypoxia potentiates the inflammatory response by TNF-α in both white and brown adipocytes and downregulates the transcription factors involved in adipocyte function.

KEYWORDS:

Adipose tissue; Cyclooxygenase-2; Hypoxia; Inducible nitric oxide synthase; Inflammation; Mitochondrial dysfunction

PMID:
25881506
DOI:
10.1016/j.bbrc.2015.04.020
[Indexed for MEDLINE]

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