Effects of hyperoxia exposure on metabolic markers and gene expression in 3T3-L1 adipocytes

Abstract

Adipose tissue often becomes poorly oxygenated in obese subjects. This feature may provide cellular mechanisms involving chronic inflammation processes such as the release of proinflammatory cytokines and macrophage infiltration. In this context, the purpose of the present study was to determine whether a hyperoxia exposure on mature adipocytes may influence the expression of some adipokines and involve favorable changes in specific metabolic variables. 3T3-L1 adipocytes (14 days differentiated) were treated with 95% oxygen for 24 h. Cell viability, intra and extracellular reactive oxygen especies (ROS) content, glucose uptake and lactate and glycerol concentrations were measured in the culture media. Also, mRNA levels of HIF-1, leptin, IL-6, MCP-1, PPAR-, adiponectin, and ANGPTL-4 were analyzed.Hyperoxia treatment increased intra and extracellular ROS content, reduced glucose uptake and lactate release and increased glucose release. It also led to an upregulation of the expression of IL-6, MCP-1 and PPAR-, while ANGPTL4 was downregulated in the hyperoxia group with respect to control. The present data shows that hyperoxia treatment seems to provoke an inflammatory response due to the release of ROS and the upregulation of pro-inflammatory adipokines, such as IL-6 and MCP-1. On the other hand, hyperoxia may have an indirect effect on the improvement of insulin sensitivity, due to the upregulation of PPAR- gene expression as well as a possible modulation of both glucose and lipid metabolic markers. To our knownledge, this is the first study analyzing the effect of hyperoxia in 3T3-L1 adipocytes.

The Circulatory and Metabolic Responses to Hypoxia in Humans – With Special Reference to Adipose Tissue Physiology and Obesity

“…However, as oxygen is known to be toxic in high concentrations, this treatment may not be healthy in terms of circulatory and metabolic function. Hyperoxia is known to decrease adipose cell viability, increase both intra- and extracellular oxidative stress, provoke inflammation, and decrease glucose uptake of adipocytes (69). Hence, based on this information on hyperoxia and reviewed knowledge regarding hypoxia, it is concluded that there is a delicate balance of healthy oxygen supply and demand in adipose tissue that determines its overall function.…”

Adipose Tissue Dysfunction and Impaired Metabolic Health in Human Obesity: A Matter of Oxygen?

“…Most of these studies have demonstrated that extremely low PO 2 induces a pro-inflammatory response in 3T3-L1 adipocytes ( 18 , 27 – 31 ), human adipocytes ( 32 ), stromal–vascular cells ( 33 , 34 ), and macrophages ( 18 , 35 ), although conflicting results have also been reported ( 36 , 37 ). On the other hand, 95% O 2 also increased pro-inflammatory gene expression and reactive oxygen species (ROS) content, and reduced glucose uptake in 3T3-L1 adipocytes ( 38 ). These in vitro studies should be interpreted with some caution, because these cells were acutely exposed to extremely low (or high) PO 2 .…”

Vitamin C in the Treatment and/or Prevention of Obesity

“…This is the case of obesity, where established hypoxia occurs at the adipose tissue level (due to adipose tissue expansion in cell number and size) causing several alterations, such as macrophage infiltration and generation of ROS, that lead to a pro-inflammatory state within that tissue (103)(104)(105)(106). Today, strong scientific evidence based on cell culture, animal, and human studies support that hypoxia plays a fundamental role in the initiation and development of obesity (107)(108)(109).…”