Adipose Tissue Hypoxia in Obesity and Its Impact on Preadipocytes and Macrophages: Hypoxia Hypothesis

  • Atilla Engin
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 960)


Obese subjects exhibit lower adipose tissue oxygen consumption in accordance with the lower adipose tissue blood flow. Thus, compared with lean subjects, obese subjects have 44% lower capillary density and 58% lower vascular endothelial growth factor (VEGF). The VEGF expression together with hypoxia-inducible transcription factor-1 (HIF-1) activity also requires phosphatidylinositol 3-kinase (PI3K)- and target of rapamycin (TOR)-mediated signaling. HIF-1alpha is an important signaling molecule for hypoxia to induce the inflammatory responses. Hypoxia affects a number of biological functions, such as angiogenesis, cell proliferation, apoptosis, inflammation and insulin resistance. Additionally, reactive oxygen radical (ROS) generation at mitochondria is responsible for propagation of the hypoxic signal. Actually mitochondrial ROS (mtROS) production, but not oxygen consumption is required for hypoxic HIF-1alpha protein stabilization. Adipocyte mitochondrial oxidative capacity is reduced in obese compared with non-obese adults. In this respect, mitochondrial dysfunction of adipocyte is associated with the overall adiposity. Furthermore, hypoxia also inhibits macrophage migration from the hypoxic adipose tissue. Alterations in oxygen availability of adipose tissue directly affect the macrophage polarization and are responsible from dysregulated adipocytokines production in obesity. Hypoxia also inhibits adipocyte differentiation from preadipocytes. In addition to stressed adipocytes, hypoxia contributes to immune cell immigration and activation which further aggravates adipose tissue fibrosis. Fibrosis is initiated in response to adipocyte hypertrophy in obesity.


Obesity Hypoxia-inducible transcription factor-1 (HIF-1) alpha Vascular endothelial growth factor (VEGF) Angiogenesis Reactive oxygen species (ROS) Mitochondrial ROS (mtROS) CAAT/enhancer binding protein (C/EBP) CAAT/enhancer binding protein (C/EBP)-homologous protein (CHOP) Adipocyte differentiation Adipose tissue blood flow Phosphatidylinositol 3-kinase (PI3K) Inducible nitric oxide synthase (iNOS) 


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Copyright information

© Springer International Publishing AG 2017

Authors and Affiliations

  1. 1.Faculty of Medicine, Department of General SurgeryGazi UniversityBesevlerTurkey
  2. 2.CankayaTurkey

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