AIMS: Hypoxia has been implicated as a cause of adipose tissue inflammation in obesity, although the inflammatory response of human adipose tissue to hypoxia is not well understood. The goal of this study was to define in vitro inflammatory responses of human adipose tissue to hypoxia and identify molecular mechanisms of hypoxia-induced inflammation. METHODS: The inflammatory milieu and responses of visceral (VAT) and subcutaneous (SAT) adipose tissue explants and purified stromovascular cells (SVFs) from obese and lean humans were studied in an in vitro hypoxic culture system using quantitative real-time PCR, ELISA, western blotting, immunofluorescence microscopy, flow cytometry and immunohistochemistry. RESULTS: Human adipose tissue in obesity demonstrates an increased leucocyte infiltrate that is greater in VAT than SAT and involves macrophages, T cells and natural killer (NK) cells. Hypoxic culture regulates inflammatory cytokine secretion and transcription of metabolic stress response genes in human adipose tissue SVF. Adipocyte diameter is increased and adipose tissue capillary density is decreased in obese participants. Inhibition of c-Jun terminal kinase (JNK) or p38 significantly attenuates hypoxia-induced SVF inflammatory responses. Hypoxia induces phosphorylation of p38 in adipose tissue. CONCLUSIONS: Human adipose tissue in obesity is characterised by a depot-specific inflammatory cell infiltrate that involves not only macrophages, but also T cells and NK cells. Hypoxia induces inflammatory cytokine secretion by human adipose tissue SVF, the primary source of which is adipose tissue macrophages. These data implicate p38 in the regulation of hypoxia-induced inflammation and suggest that alterations in adipocyte diameter and adipose tissue capillary density may be potential underlying causes of adipose tissue hypoxia.
AIMS: Hypoxia has been implicated as a cause of adipose tissue inflammation in obesity, although the inflammatory response of humanadipose tissue to hypoxia is not well understood. The goal of this study was to define in vitro inflammatory responses of humanadipose tissue to hypoxia and identify molecular mechanisms of hypoxia-induced inflammation. METHODS: The inflammatory milieu and responses of visceral (VAT) and subcutaneous (SAT) adipose tissue explants and purified stromovascular cells (SVFs) from obese and lean humans were studied in an in vitro hypoxic culture system using quantitative real-time PCR, ELISA, western blotting, immunofluorescence microscopy, flow cytometry and immunohistochemistry. RESULTS:Humanadipose tissue in obesity demonstrates an increased leucocyte infiltrate that is greater in VAT than SAT and involves macrophages, T cells and natural killer (NK) cells. Hypoxic culture regulates inflammatory cytokine secretion and transcription of metabolic stress response genes in humanadipose tissue SVF. Adipocyte diameter is increased and adipose tissue capillary density is decreased in obeseparticipants. Inhibition of c-Jun terminal kinase (JNK) or p38 significantly attenuates hypoxia-induced SVF inflammatory responses. Hypoxia induces phosphorylation of p38 in adipose tissue. CONCLUSIONS:Humanadipose tissue in obesity is characterised by a depot-specific inflammatory cell infiltrate that involves not only macrophages, but also T cells and NK cells. Hypoxia induces inflammatory cytokine secretion by humanadipose tissue SVF, the primary source of which is adipose tissue macrophages. These data implicate p38 in the regulation of hypoxia-induced inflammation and suggest that alterations in adipocyte diameter and adipose tissue capillary density may be potential underlying causes of adipose tissue hypoxia.
Authors: Barbara Kabon; Angelika Nagele; Dayakar Reddy; Chris Eagon; James W Fleshman; Daniel I Sessler; Andrea Kurz Journal: Anesthesiology Date: 2004-02 Impact factor: 7.892
Authors: Hyunwon Yang; Yun-Hee Youm; Bolormaa Vandanmagsar; Anthony Ravussin; Jeffrey M Gimble; Frank Greenway; Jacqueline M Stephens; Randall L Mynatt; Vishwa Deep Dixit Journal: J Immunol Date: 2010-06-25 Impact factor: 5.422
Authors: Stuart P Weisberg; Daniel McCann; Manisha Desai; Michael Rosenbaum; Rudolph L Leibel; Anthony W Ferrante Journal: J Clin Invest Date: 2003-12 Impact factor: 14.808
Authors: Gábor Winkler; Sándor Kiss; László Keszthelyi; Zoltán Sápi; Iván Ory; Ferenc Salamon; Margit Kovács; Péter Vargha; Orsolya Szekeres; Gábor Speer; István Karádi; Marta Sikter; Edit Kaszás; Otto Dworak; Gábor Gerö; Károly Cseh Journal: Eur J Endocrinol Date: 2003-08 Impact factor: 6.664
Authors: Lindsey A Muir; Christopher K Neeley; Kevin A Meyer; Nicki A Baker; Alice M Brosius; Alexandra R Washabaugh; Oliver A Varban; Jonathan F Finks; Brian F Zamarron; Carmen G Flesher; Joshua S Chang; Jennifer B DelProposto; Lynn Geletka; Gabriel Martinez-Santibanez; Niko Kaciroti; Carey N Lumeng; Robert W O'Rourke Journal: Obesity (Silver Spring) Date: 2016-03 Impact factor: 5.002
Authors: Trivia P Frazier; James B McLachlan; Jeffrey M Gimble; Hugh A Tucker; Brian G Rowan Journal: Stem Cells Dev Date: 2014-03-11 Impact factor: 3.272