Hypoxia dysregulates the production of adiponectin and plasminogen activator inhibitor-1 independent of reactive oxygen species in adipocytes

Chen, Baoying; Lam, Karen S.L.; Wang, Yudong; Wu, Donghai; Lam, Michael C.; Shen, Jiangang; Wong, L. S. Ling; Hoo, Ruby L.C.; Zhang, Jialiang; Xu, Aimin

doi:10.1016/j.bbrc.2006.01.004

Cited by 203 publications

(164 citation statements)

References 52 publications

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“…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: 88%

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

et al. 2012

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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.

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“…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: 88%

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

et al. 2012

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“…The effects of the local AT hypoxia have been investigated both in isolated murine adipocytes and in animal models (4,(22)(23)(24)(25). These papers suggest that many adipokines that are related to inflammation, such as macrophage migration inhibitory factor (MIF), the matrix metalloproteinases MMP2 and MMP9, IL-6, Angplt4, PAI-1, VEGF, and leptin are all upregulated by hypoxia (22)(23)(24)(25).…”

Section: Macrophages Major Constituents Of At and Mediators Of Remodmentioning

confidence: 99%

Adipose tissue remodeling and obesity

Sun¹,

Kusminski²,

Scherer³

2011

J. Clin. Invest.

1,552

1,381

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To fulfill its role as the major energy-storing tissue, adipose has several unique properties that cannot be seen in any other organ, including an almost unlimited capacity to expand in a non-transformed state. As such, the tissue requires potent mechanisms to remodel, acutely and chronically. Adipocytes can rapidly reach the diffusional limit of oxygen during growth; hypoxia is therefore an early determinant that limits healthy expansion. Proper expansion requires a highly coordinated response among many different cell types, including endothelial precursor cells, immune cells, and preadipocytes. There are therefore remarkable similarities between adipose expansion and growth of solid tumors, a phenomenon that presents both an opportunity and a challenge, since pharmacological interventions supporting healthy adipose tissue adaptation can also facilitate tumor growth. IntroductionAdipose tissue (AT) can respond rapidly and dynamically to alterations in nutrient deprivation and excess through adipocyte hypertrophy and hyperplasia, thereby fulfilling its major role in wholebody energy homeostasis. AT remodeling is an ongoing process that is pathologically accelerated in the obese state, and thus, features such as reduced angiogenic remodeling, ECM overproduction, a heightened state of immune cell infiltration and subsequent proinflammatory responses prevail in many obese fat-pads (1). However, not all AT expansion is necessarily associated with pathological changes. The concept of the "metabolically healthy obese" state (2) suggests that some individuals can preserve systemic insulin sensitivity on the basis of "healthy" AT expansion, bypassing all of the aforementioned pathological consequences associated with obesity (3), thereby also avoiding the obesity-associated lipotoxic side effects. Many physiologically relevant processes important for human AT remodeling can be studied in rodent models, with the added advantage that processes related to AT expansion and reduction can occur at an extremely rapid rate. A 24-hour fast in a mouse is associated with a dramatic loss of AT mass and an acute remodeling process that involves rapid infiltration of macrophages; moreover, merely 24 to 48 hours of exposure to a high-fat diet (HFD) can cause a prompt increase in adipocyte size (4). AT is therefore an ideal model system to study rapid alterations in tissue expansion and reduction, as it adapts to a differential nutrient supply. Here, we will focus on key aspects of the intricate dynamics of AT remodeling and subsequent inflammatory consequences that arise from obesity.

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“…Other major adipokines, murine or human, whose expression is stimulated by hypoxia include angiopoietin-like protein 4 (Angptl4), interleukin-6 (IL-6), macrophage migration inhibitory factor (MIF), and vascular endothelial growth factor (VEGF), while the non-adipokines include the GLUT-1 and GLUT-3 facilitative glucose transporters (Lolmède et al 2003, Hosogai et al 2007, Ye et al 2007. By contrast, adiponectin and haptoglobin expression is inhibited by low O 2 tension (Chen et al 2006, Hosogai et al 2007. Hypoxia-induced changes in adipokine production have been suggested to underlie the development of the inflammatory response in adipose tissue, which occurs in the obese state (Trayhurn & Wood 2004).…”

Section: Introductionmentioning

confidence: 99%

Hypoxia induces leptin gene expression and secretion in human preadipocytes: differential effects of hypoxia on adipokine expression by preadipocytes

Wang¹,

Wood²,

Trayhurn³

2008

Journal of Endocrinology

129

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The effect of hypoxia on the expression and secretion of major adipokines by human preadipocytes has been examined. Hypoxia (1% O 2 ) led to an increase in the HIF-1a transcription factor subunit in cultured preadipocytes, as did incubation with the hypoxia mimetic CoCl 2 . Leptin mRNA was essentially undetectable in preadipocytes incubated under normoxia (21% O 2 ), but exposure to 1% O 2 , or CoCl 2 , for 4 or 24 h resulted in an induction of leptin gene expression (measured by real-time PCR). Immunoreactive leptin was not detected in the medium from normoxic preadipocytes, but was present in the medium from the hypoxic cells. Hypoxia stimulated expression of the GLUT-1 facilitative glucose transporter gene and the vascular endothelial growth factor (VEGF) gene in preadipocytes, as in adipocytes. PPARg and aP2 mRNA levels, markers of adipocyte differentiation, were reduced by hypoxia in both cell types. In marked contrast to adipocytes, interleukin-6 (IL-6), angiopoietin-like protein 4, and plasminogen activator inhibitor-1 expression by preadipocytes was not stimulated by low O 2 tension. Consistent with the gene expression results, VEGF release into the medium from preadipocytes was increased by hypoxia, but there was no change in IL-6 secretion. It is concluded that hypoxia induces human preadipocytes to synthesize and secrete leptin. Preadipocytes and adipocytes differ in their responsiveness to low O 2 tension, maturation of the response to hypoxia developing on differentiation.

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Hypoxia dysregulates the production of adiponectin and plasminogen activator inhibitor-1 independent of reactive oxygen species in adipocytes

Cited by 203 publications

References 52 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

Adipose tissue remodeling and obesity

Hypoxia induces leptin gene expression and secretion in human preadipocytes: differential effects of hypoxia on adipokine expression by preadipocytes

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