Dysregulation of the expression and secretion of inflammation-related adipokines by hypoxia in human adipocytes

Wang, Bohan; Wood, I. Stuart; Trayhurn, Paul

doi:10.1007/s00424-007-0301-8

Cited by 341 publications

(336 citation statements)

References 53 publications

Supporting

Mentioning

310

Contrasting

Unclassified

Order By: Relevance

“…It is known that IL-6 suppresses adiponectin gene expression [7,12,51]. However, mRNA levels of this antiinflammatory adipokine did not show a significant change.…”

Section: Discussionmentioning

confidence: 90%

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

et al. 2012

View full text Add to dashboard Cite

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.

show abstract

“…It is known that IL-6 suppresses adiponectin gene expression [7,12,51]. However, mRNA levels of this antiinflammatory adipokine did not show a significant change.…”

Section: Discussionmentioning

confidence: 90%

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

et al. 2012

View full text Add to dashboard Cite

show abstract

“…They are mainly from macrophages, but also secreted by adipocytes. 32 Obesity is considered a low-grade inflammatory state 33 and proinflammatory cytokines were thought to be involved in the development of obesity-related insulin resistance and cardiovascular diseases. However, not all studies found a correlation between plasma proinflammatory cytokine levels and obesity.…”

Section: Introductionmentioning

confidence: 99%

Lack of association between body mass index and plasma adiponectin levels in healthy adults

Kuo

2011

Int J Obes

View full text Add to dashboard Cite

Objectives: To test the hypothesis that obesity (increase in fat mass) independently affects the level of adipokines: adiponectin, tumor necrosis factor-a (TNFa) and interleukin (IL)-6. Methods: Publications in the past decade reporting adult plasma adiponectin, leptin, TNFa and/or IL-6 levels were compiled. Mean gender-specific values were extracted from studies that included medical screening to confirm physical health (43 groups, total 4852 subjects). Correlation analysis was conducted between adipokine levels and body mass index (BMI), a widely used estimate of adiposity. Results: For healthy lean to obese adults of both genders, no significant correlation between plasma adiponectin and BMI was detected. There was also no gender difference in plasma adiponectin level. In contrast, leptin levels showed a positive correlation with BMI in both genders, and women had significantly higher levels of plasma leptin consistent with a higher percentage of body fat. The proinflammatory cytokine TNFa failed to show correlation with BMI. Although IL-6 showed a positive correlation with BMI in women, the obesity-related increase was very limited. Conclusions: Data analysis based on studies performed on healthy adults did not support the hypothesis that obesity independently affects the plasma level of adiponectin and TNFa. Reported obesity-related changes in plasma adipokine levels may be a consequence of obesity-related metabolic disorders. Future studies are especially needed to understand the homeostasis of adiponectin.

show abstract

“…Adipose tissue, which consists of preadipocytes, adipocytes, and vascular cells, has important endocrine functions including the secretion of adipokines (TNF, IL-6, leptin, adiponectin and more) and monocyte chemoattractant protein 1 (MCP-1) [80,81]. During inflammation, infiltrating macrophages are found in adipose tissue.…”

Section: Proteotoxic Stress In the Pathogenesis Of Diseases Not Formementioning

confidence: 99%

Protein misfolding and dysregulated protein homeostasis in autoinflammatory diseases and beyond

et al. 2015

View full text Add to dashboard Cite

Cells have a number of mechanisms to maintain protein homeostasis, including proteasomemediated degradation of ubiquitinated proteins and autophagy, a regulated process of 'self-eating' where the contents of entire organelles can be recycled for other uses. The unfolded protein response prevents protein overload in the secretory pathway. In the past decade, it has become clear that these fundamental cellular processes also help contain inflammation though degrading pro-inflammatory protein complexes such as the NLRP3 inflammasome. Signaling pathways such as the UPR can also be co-opted by tolllike receptor and mitochondrial reactive oxygen species signaling to induce inflammatory responses.Mutations that alter key inflammatory proteins, such as NLRP3 or TNFR1, can overcome normal protein homeostasis mechanisms, resulting in autoinflammatory diseases. Conversely, Mendelian defects in the proteasome cause protein accumulation, which can trigger interferon-dependent autoinflammatory disease. In non-Mendelian inflammatory diseases, polymorphisms in genes affecting the UPR or autophagy pathways can contribute to disease, and in diseases not formerly considered inflammatory such as neurodegenerative conditions and type 2 diabetes, there is increasing evidence that cell intrinsic or environmental alterations in protein homeostasis may contribute to pathogenesis.3 Cells must maintain a delicate balance between the demands for protein synthesis and the need to avoid accumulation of incompletely processed or unfolded proteins that can accumulate under normal conditions and even more so when cells face a variety of stresses. The unfolded protein response (UPR) is an evolutionarily conserved mechanism to maintain cellular homeostasis by preventing the accumulation of misfolded proteins in the endoplasmic reticulum (ER). Disturbed protein folding in the ER is primarily detected by three transmembrane (TM) proteins: activating transcription factor 6 (ATF6), inositol-requiring transmembrane kinase/endonuclease 1 (IRE1) and pancreatic ER kinase (PERK). The combined action of these sensors reduces global protein synthesis while upregulating the production of chaperone proteins that can stabilize misfolded proteins. Apart from ER homeostasis, the UPR can modulate other biological functions, including apoptosis, protein secretion, and as we will discuss further, inflammatory responses [1,2].A series of molecular changes are initiated in response to cellular stressors in order to minimize damage caused by unfavorable environmental conditions, such as temperature changes, toxins (e.g. bacterial, chemical), radiation, mechanical damage, nutritional status as well as incompletely folded proteins intracellularly (Figure 1). The UPR serves the adaptive purpose of protecting the cell by activating a series of mechanisms including the induction of molecular chaperones to assist with correct folding -e.g. heat shock proteins and foldases. Interestingly there are a number of connections between the UPR and inflammatory signaling pat...

show abstract

Dysregulation of the expression and secretion of inflammation-related adipokines by hypoxia in human adipocytes

Cited by 341 publications

References 53 publications

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

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

Lack of association between body mass index and plasma adiponectin levels in healthy adults

Protein misfolding and dysregulated protein homeostasis in autoinflammatory diseases and beyond

Contact Info

Product

Resources

About