Effects of hypoxia on the expression of proangiogenic factors in differentiated 3T3-F442A adipocytes

Lolmède, Karine; Front, Véronique Durand de Saint; Galitzky, Jean; Lafontan, Max; Bouloumié, Anne

doi:10.1038/sj.ijo.0802407

Cited by 191 publications

(159 citation statements)

References 38 publications

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“…Hence, an alternative approach that can reduce the food intake with minimal side effects emerged as another cautiously accepted choice in obesity control. 5,6 Platycodi Radix (Chinese Jiegeng, Japanese Kikyo, Korean Doraji) is the root of Platycodon grandiflorum A. De (Campanulaceae).…”

Section: Introductionmentioning

confidence: 99%

Antiobese and hypolipidemic effects of platycodin saponins in diet-induced obese rats: evidences for lipase inhibition and calorie intake restriction

Shim

et al. 2005

Int J Obes

122

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OBJECTIVE:To investigate how and to what extent platycodin saponin (PS) from Platycodi Radix exerts a favorable influence on obesity and hyperlipidemia. DESIGN: Sprague-Dawley rats were fed with a high fat (HF) diet for 4 weeks and then the animals were treated with 35 or 70 mg/kg of PS for another 4 weeks. Changes in body weight and daily calorie intake were measured regularly during the experimental period and the degree of linear correlation for the above two variables was further analyzed. The in vitro lipase inhibition of each PS compound and the in vivo fecal lipid excretion were examined in hope of revealing their relationship. The concentrations of hepatic triglyceride and cholesterol in serum. RESULTS: The body weight reduction (1374% vs HF control, Po0.05) by PS administration was highly correlated to the food intake restriction (Pearson's linear coefficient r ¼ 0.752, Po0.005). The in vitro inhibition of lipase by each isolated compound and mixture of PS were virtually identical. Consequently, the fecal TG excretion was increased by 2.1-3.2 folds depending on the dose of PS. The serum TG and LDL-cholesterol concentrations were decreased without noticeable changes in HDLcholesterol levels. Concomitantly, the contents of the hepatic TG, cholesterol, and the liver surface fat pads were decreased in ubiquity, but no noticeable biochemical abnormalities or histological tissue damages were observed. CONCLUSIONS: The administration of PS produced profound effects on the control of obesity and lipid metabolism, which resulted in LDL-cholesterol reduction. PS also caused a remarkable reduction in calorie intake, which was highly correlated to the body weight loss. These results suggest that PS has a greater role in antiobesity, hypolipidemia, and liver protection than previously thought. Hence, PS could be a potential therapeutic alternative in the treatment of obesity and hyperlipidemia.

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Section: Introductionmentioning

confidence: 99%

Antiobese and hypolipidemic effects of platycodin saponins in diet-induced obese rats: evidences for lipase inhibition and calorie intake restriction

Shim

et al. 2005

Int J Obes

122

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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%

“…Several important hypoxia-associated genes, such as leptin and VEGF, are directly regulated by HIF-1 (25). As a transcription factor, HIF-1 functions as a heterodimer, consisting of an oxygensensitive HIF-1α subunit and a constitutively expressed HIF-1β subunit.…”

Section: Macrophages Major Constituents Of At and Mediators Of Remodmentioning

confidence: 99%

Adipose tissue remodeling and obesity

Sun¹,

Kusminski²,

Scherer³

2011

J. Clin. Invest.

1,509

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.…”

Section: Introductionmentioning

confidence: 99%

“…A number of factors that regulate leptin production by white adipocytes have been identified, and these include insulin, PPARg agonists, and the sympathetic nervous system (Harris 2000, Trayhurn & Beattie 2001. Leptin is a hypoxia-sensitive gene; its expression being stimulated in adipocytes by low O 2 tension (Grosfeld et al 2002b, Lolmède et al 2003, Polotsky et al 2003, Hausman & Richardson 2004, through transcriptional regulation by the hypoxia-inducible transcription factor, HIF-1 (Grosfeld et al 2001, Ambrosini et al 2002. The induction of leptin expression by hypoxia has also been reported in other cell types, including human trophoblast cell lines (Mise et al 1998, Grosfeld et al 2001, Meissner et al 2005, MCF-7 breast cancer cells (Cascio et al 2008), and ectopic endometriotic stromal cells (Wu et al 2007).…”

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

126

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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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Effects of hypoxia on the expression of proangiogenic factors in differentiated 3T3-F442A adipocytes

Cited by 191 publications

References 38 publications

Antiobese and hypolipidemic effects of platycodin saponins in diet-induced obese rats: evidences for lipase inhibition and calorie intake restriction

Antiobese and hypolipidemic effects of platycodin saponins in diet-induced obese rats: evidences for lipase inhibition and calorie intake restriction

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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