Abstract
Metabolic disturbances in white adipose tissue in obese individuals contribute to the pathogenesis of insulin resistance and the development of type 2 diabetes mellitus. Impaired insulin action in adipocytes is associated with elevated lipolysis and increased free fatty acids leading to ectopic fat deposition in liver and skeletal muscle. Chronic adipose tissue hypoxia has been suggested to be part of pathomechanisms causing dysfunction of adipocytes. Hypoxia can provoke oxidative stress in human and animal adipocytes and reduce the production of beneficial adipokines, such as adiponectin. However, time-dose responses to hypoxia relativize the effects of hypoxic stress. Long-term exposure of fat cells to hypoxia can lead to the production of beneficial substances such as leptin. Knowledge of time-dose responses of hypoxia on white adipose tissue and the time course of generation of oxidative stress in adipocytes is still scarce. This paper reviews the potential links between adipose tissue hypoxia, oxidative stress, mitochondrial dysfunction, and low-grade inflammation caused by adipocyte hypertrophy, macrophage infiltration and production of inflammatory mediators.
Highlights
Metabolic disturbances in white adipose tissue in obese individuals contribute to the pathogenesis of insulin resistance and the development of type 2 diabetes mellitus
Among the inflammatory markers, which mostly go in accordance with hypoxia-inducible factor (HIF) and glutathione, tumor necrosis factor (TNF)- already reached its peak after 2 h
All these data demonstrate how important it is to consider the time response to hypoxia, and question acute effects in adipocytes after seconds of oxygen desaturation, as occurring, for instance, during intermittent hypoxia in obstructive sleep apnea. How this type of intermittent hypoxia may have accumulative effects. In any case it has to be taken into account that after some hours of hypoxia, adipocytes start to adapt to the hypoxic stimulus accompanied by oxidative stress reduction, and that older adipocytes seem to be somewhat more “relaxed” in their reaction to hypoxia compared to younger ones
Summary
In order to understand under which circumstances hypoxia can induce oxidative stress in adipocytes it is useful to consider some basic physical principles. This is important because the perception of oxidative stress and fast reactions in response to hypoxia usually relate to tissues with a high blood perfusion and a solubility coefficient similar to that of water. Assumptions are based on an adipocyte volume of 500 nL [4] and a lipid vacuole fraction of 80% of cell volume
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