Oxygenation of adipose tissue: A human perspective

Abstract

Obesity is a complex disorder of excessive adiposity, and is associated with adverse health effects such as cardiometabolic complications, which are to a large extent attributable to dysfunctional white adipose tissue. Adipose tissue dysfunction is characterized by adipocyte hypertrophy, impaired adipokine secretion, a chronic low-grade inflammatory status, hormonal resistance and altered metabolic responses, together contributing to insulin resistance and related chronic diseases. Adipose tissue hypoxia, defined as a relative oxygen deficit, in obesity has been proposed as a potential contributor to adipose tissue dysfunction, but studies in humans have yielded conflicting results. Here, we will review the role of adipose tissue oxygenation in the pathophysiology of obesity-related complications, with a specific focus on human studies. We will provide an overview of the determinants of adipose tissue oxygenation, as well as the role of adipose tissue oxygenation in glucose homeostasis, lipid metabolism and inflammation. Finally, we will discuss the putative effects of physiological and experimental hypoxia on adipose tissue biology and whole-body metabolism in humans. We conclude that several lines of evidence suggest that alteration of adipose tissue oxygenation may impact metabolic homeostasis, thereby providing a novel strategy to combat chronic metabolic diseases in obese humans.

Keywords: adipose tissue; hypoxia; inflammation; metabolism; obesity; oxygen.

Figure 1

Characteristics of lean healthy and obese dysfunctional white adipose tissue. Adipose tissue dysfunction is characterized by adipocyte hypertrophy, impaired adipokine secretion, a chronic low‐grade inflammation, apoptosis, extracellular matrix remodelling, hormonal resistance, vascular rarefaction, decreased adipose tissue blood flow and altered metabolic responses, together contributing to insulin resistance and related chronic diseases. ER, endoplasmic reticulum

Figure 2

Adipocyte substrate metabolism, adipocyte gene expression and adipokine secretion are affected by alteration of oxygen partial pressure (pO₂). Both the severity and the duration of hypoxia exposure seem to impact cellular processes, as explained in more detail in the text. Panel A shows the effects of acute exposure to severe hypoxia (usually 1% O₂ for <24 h), while panel B illustrates the putative effects of prolonged, mild hypoxia exposure (usually 5%‐10% O₂ for 7‐14 d) on adipocyte biology. ER, endoplasmic reticulum; FA, fatty acids; FATP/CD36, fatty acid transporters; GLUT, glucose transporter; IR, insulin receptor; MCTs, monocarboxylate transporters; pO₂, oxygen partial pressure; TAG, triacylglycerol. ↑, increase; ↓, decrease; ↔, unchanged; ?, not determined

Figure 3

Putative impact of (moderate) hypoxia exposure on whole‐body, skeletal muscle and adipose tissue physiology. O₂, oxygen; pO₂, oxygen partial pressure