title: Hypoxia potentiates tumor necrosis factor-α induced expression of inducible nitric oxide synthase and cyclooxygenase-2 in white and brown adipocytes.
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.
authors.affiliation: 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.
authors.forename: Indranil
authors.initials: I
authors.lastname: Bhattacharya
authors.affiliation: Department of Internal Medicine, University Hospital of Zurich, Switzerland.
authors.forename: Ana Pérez
authors.initials: AP
authors.lastname: Domínguez
authors.affiliation: 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.
authors.forename: Katja
authors.initials: K
authors.lastname: Drägert
authors.affiliation: 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.
authors.forename: Rok
authors.initials: R
authors.lastname: Humar
authors.affiliation: 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.
authors.forename: Elvira
authors.initials: E
authors.lastname: Haas
authors.affiliation: 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.
authors.forename: Edouard J
authors.initials: EJ
authors.lastname: Battegay
mesh_terms: D017667:Adipocytes / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D052437:Adipocytes, Brown / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D052438:Adipocytes, White / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D000818:Animals; D015687:Cell Hypoxia; D002460:Cell Line; D051546:Cyclooxygenase 2 / Q000032:analysis / Q000235:genetics*; D005786:Gene Expression Regulation; D000860:Hypoxia / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D007249:Inflammation / Q000235:genetics / Q000276:immunology / Q000473:pathology; D051379:Mice; D052247:Nitric Oxide Synthase Type II / Q000032:analysis / Q000235:genetics*; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology*
chemical_list: D014409:Tumor Necrosis Factor-alpha; D052247:Nitric Oxide Synthase Type II; D051546:Cyclooxygenase 2
keywords: Adipose tissue; Cyclooxygenase-2; Hypoxia; Inducible nitric oxide synthase; Inflammation; Mitochondrial dysfunction