Regulation of HIF-1α activity in adipose tissue by obesity-associated factors: adipogenesis, insulin, and hypoxia

He, Qing; Gao, Zhan‐Guo; Yin, Jun; Zhang, Jin; Yun, Zhong; Ye, Jianping

doi:10.1152/ajpendo.00626.2010

Cited by 190 publications

(149 citation statements)

References 64 publications

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“…In many of the pathological situations described above (5,7,8,12,16,17), HIFs are activated in response to the hypoxic and inflammatory microenvironment. HIFs represent the primary O 2 -sensing transcription factors (18)(19)(20)(21) as heterodimers comprised of an O 2 -sensitive α subunit (HIF-α) and a constitutively expressed β subunit (HIF-1β or aryl hydrocarbon receptor nuclear translocator [ARNT]).…”

Section: Hypoxia and Hypoxia-inducible Factorsmentioning

confidence: 99%

Hypoxia-inducible factors: key regulators of myeloid cells during inflammation

Lin¹,

Simon²

2016

Journal of Clinical Investigation

119

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Section: Hypoxia and Hypoxia-inducible Factorsmentioning

confidence: 99%

Hypoxia-inducible factors: key regulators of myeloid cells during inflammation

Lin¹,

Simon²

2016

Journal of Clinical Investigation

119

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“…Since the increase in vascular density is essential for adipose tissue expansion, with endothelial cells actively promoting the development of preadipocytes and growth of mature adipocytes, apelin has been proposed to contribute to the development of new vasculature in expanding fat depot [149] . Several studies have demonstrated that apelin is a potent angiogenic factor [149] , grossly equivalent to vascular endothelial cell growth factor and, like other angiogenic factors, its gene is upregulated under hypoxia condition [150] . Hypoxia induces expression and secretion of apelin in both human and murine adipocytes, through the hypoxia-inducible transcriptor factor 1a.…”

Section: Apelinmentioning

confidence: 99%

Adipose tissue and vascular inflammation in coronary artery disease

Golia¹,

Limongelli²,

Natale³

et al. 2014

WJC

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Obesity has become an important public health issue in Western and developing countries, with well known metabolic and cardiovascular complications. In the last decades, evidence have been growing about the active role of adipose tissue as an endocrine organ in determining these pathological consequences. As a consequence of the expansion of fat depots, in obese subjects, adipose tissue cells develope a phenotypic modification, which turns into a change of the secretory output. Adipocytokines produced by both adipocytes and adipose stromal cells are involved in the modulation of glucose and lipid handling, vascular biology and, moreover, participate to the systemic inflammatory response, which characterizes obesity and metabolic syndrome. This might represent an important pathophysiological link with atherosclerotic complications and cardiovascular events. A great number of adipocytokines have been described recently, linking inflammatory mileu and vascular pathology. The understanding of these pathways is crucial not only from a pathophysiological point of view, but also to a better cardiovascular disease risk stratification and to the identification of possible therapeutic targets. The aim of this paper is to review the role of Adipocytokines as a possible link between obesity and vascular disease. Key words: Adipocytokines; Obesity; Metabolic syndrome; Coronary artery disease; Inflammation Core tip: Our article, provide a comprehensive review of the evidence about adipose tissue and cardiovascular risk, focusing on the pathophysiological and clinical role of fat-derived mediators, the so-called adipocytokines.

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“…HIF-1␣ is a primary transcription factor that is activated by hypoxia to regulate gene expression, although HIF-1␣ is also regulated by insulin and adipogenesis in obesity (17). To test the role of HIF-1␣ in the regulation of 11␤-HSD1 expression, we compared 11␤-HSD1 expression in WT and HIF-1␣-null MEFs in this study.…”

Section: ␤-Hsd1 Is Inducted By Nf-bmentioning

confidence: 99%

Regulation of 11β-HSD1 expression during adipose tissue expansion by hypoxia through different activities of NF-κB and HIF-1α

Lee

Gao

2013

American Journal of Physiology-Endocrinology and Metabolism

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Lee JH, Gao Z, Ye J. Regulation of 11␤-HSD1 expression during adipose tissue expansion by hypoxia through different activities of NF-B and HIF-1␣. Am J Physiol Endocrinol Metab 304: E1035-E1041, 2013. First published March 19, 2013; doi:10.1152/ajpendo.00029.2013.-11␤-Hydroxysteroid dehydrogenase type 1 (11␤-HSD1) is involved in the pathogenesis of type 2 diabetes by generating active glucocorticoids (cortisol and corticosterone) that are strong inhibitors of angiogenesis. However, the mechanism of 11␤-HSD1 gene expression and its relationship to adipose angiogenesis are largely unknown. To address this issue, we examined 11␤-HSD1 expression in visceral and subcutaneous adipose tissue (AT) of diet-induced obese (DIO) mice during weight gain and investigated the gene regulation by hypoxia in vitro. 11␤-HSD1 mRNA was reduced in the adipose tissues during weight gain in DIO mice, and the reduction was associated with an elevated expression of angiogenic factors. In vitro, 11␤-HSD1 expression was induced in mRNA and protein by hypoxia. Of the two transcription factors activated by hypoxia, the nuclear factor-B (NF-B) enhanced but the hypoxia inducible factor-1␣ (HIF-1␣) reduced 11␤-HSD1 expression. 11␤-HSD1 expression was elevated by NF-B in epididymal fat of aP2-p65 mice. The hypoxia-induced 11␤-HSD1 expression was attenuated by NF-B inactivation in p65-deficient cells but enhanced by HIF-1 inactivation in HIF-1␣-null cells. These data suggest that 11␤-HSD1 expression is upregulated by NF-B and downregulated by HIF-1␣. During AT expansion in DIO mice, the reduction of 11␤-HSD1 expression may reflect a dominant HIF-1␣ activity in the adipose tissue. This study suggests that NF-B may mediate the inflammatory cytokine signal to upregulate 11␤-HSD1 expression.11␤-hydroxysteroid dehydrogenase type 1; nuclear factor-B; hypoxiainducible factor-1␣; hypoxia; hyperinsulinemia; angiogenesis; inflammation; obesity; type 2 diabetes 11␤-HYDROXYSTEROID DEHYDROGENASE TYPE 1 (11␤-HSD1) that converts inactive glucocorticoids (GCs; cortisone and 11-dehydrocorticosterone) into active GCs (cortisol and corticosterone) plays a role in the pathogenesis of insulin resistance. Global inactivation of 11␤-HSD1 by gene knockout prevents insulin resistance and reduces hepatic gluconeogenesis in obese mice (21). 11␤-HSD1 overexpression in adipose tissue (AT) generates visceral obesity and systemic insulin resistance in transgenic mice (23). Liver-specific overexpression of 11␤-HSD1 leads to insulin resistance in the absence of obesity in mice (31). Conversely, global inactivation of the 11␤-HSD1 gene protects mice from diet-induced obesity (21,25,26). 11␤-HSD1 has been a drug target in the study of insulin resistance, and its inhibition using a pharmacological approach improves insulin sensitivity in diabetic mice (2). 11␤-HSD1 is expressed in many cell types, including adipocytes, and the expression is increased during adipocyte differentiation (7). 11␤-HSD1 elevation in adipocytes is proposed to be a common molecular etiology for visceral obe...

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Regulation of HIF-1α activity in adipose tissue by obesity-associated factors: adipogenesis, insulin, and hypoxia

Cited by 190 publications

References 64 publications

Hypoxia-inducible factors: key regulators of myeloid cells during inflammation

Hypoxia-inducible factors: key regulators of myeloid cells during inflammation

Adipose tissue and vascular inflammation in coronary artery disease

Regulation of 11β-HSD1 expression during adipose tissue expansion by hypoxia through different activities of NF-κB and HIF-1α

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