Characterization of the inflammatory and metabolic profile of adipose tissue in a mouse model of chronic hypoxia

Bram van den Borst, Annemie M. W. J. Schols, Chiel de Theije, Agnes W. Boots, S. Eleonore Köhler, Gijs H. Goossens, Harry R. Gosker


In both obesity and chronic obstructive pulmonary disease (COPD), altered oxygen tension in adipose tissue (AT) has been suggested to evoke AT dysfunction, subsequently contributing to metabolic complications. Studying the effects of chronic hypoxia on AT function will add to our understanding of the complex pathophysiology of alterations in AT inflammation, metabolism, and mass observed in both obesity and COPD. This study investigated the inflammatory and metabolic profile of AT after chronic hypoxia. Fifty-two-week-old C57Bl/6J mice were exposed to chronic hypoxia (8% O2) or normoxia for 21 days, after which AT and plasma were collected. Adipocyte size, AT gene expression of inflammatory and metabolic genes, AT macrophage density, and circulating adipokine concentrations were measured. Food intake and body weight decreased upon initiation of hypoxia. However, whereas food intake normalized after 10 days, lower body weight persisted. Chronic hypoxia markedly reduced AT mass and adipocyte size. AT macrophage density and expression of Emr1, Ccl2, Lep, and Tnf were decreased, whereas Serpine1 and Adipoq expression levels were increased after chronic hypoxia. Concomitantly, chronic hypoxia increased AT expression of regulators of oxidative metabolism and markers of mitochondrial function and lipolysis. Circulating IL-6 and PAI-1 concentrations were increased, and leptin concentration was decreased after chronic hypoxia. Chronic hypoxia is associated with decreased rather than increased AT inflammation, and markedly decreased fat mass and adipocyte size. Furthermore, our data indicate that chronic hypoxia is accompanied by significant alterations in AT metabolic gene expression, pointing toward an enhanced AT metabolic rate.

  • inflammation
  • COPD
  • oxidative metabolism
  • lipolysis
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