American journal of respiratory cell and molecular biology, 2017-04, Vol.56 (4), p.477-487
2017
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Details
- Autor(en) / Beteiligte
- Titel
- Visceral White Adipose Tissue after Chronic Intermittent and Sustained Hypoxia in Mice
- Ist Teil von
- American journal of respiratory cell and molecular biology, 2017-04, Vol.56 (4), p.477-487
- Ort / Verlag
- United States: American Thoracic Society
- Erscheinungsjahr
- 2017
- Quelle
- Free E-Journal (出版社公開部分のみ）
- Beschreibungen/Notizen
- Angiogenesis, a process induced by hypoxia in visceral white adipose tissues (vWAT) in the context of obesity, mediates obesity-induced metabolic dysfunction and insulin resistance. Chronic intermittent hypoxia (IH) and sustained hypoxia (SH) induce body weight reductions and insulin resistance of different magnitudes, suggesting different hypoxia inducible factor (HIF)-1α-related activity. Eight-week-old male C57BL/6J mice (n = 10-12/group) were exposed to either IH, SH, or room air (RA). vWAT were analyzed for insulin sensitivity (phosphorylated (pAKT)/AKT), HIF-1α transcription using chromatin immunoprecipitation (ChIP)-sequencing, angiogenesis using immunohistochemistry, and gene expression of different fat cell markers and HIF-1α gene targets using quantitative polymerase chain reaction or microarrays. Body and vWAT weights were reduced in hypoxia (SH > IH > RA; P < 0.001), with vWAT in IH manifesting vascular rarefaction and increased proinflammatory macrophages. HIF-1α ChIP-sequencing showed markedly increased binding sites in SH-exposed vWAT both at 6 hours and at 6 weeks compared with IH, the latter also showing decreased vascular endothelial growth factor, endothelial nitric oxide synthase, P2RX5, and PAT2 expression, and insulin resistance (IH > > > SH = RA; P < 0.001). IH induces preferential whitening of vWAT, as opposed to prominent browning in SH. Unlike SH, IH elicits early HIF-1α activity that is unsustained over time and is accompanied by concurrent vascular rarefaction, inflammation, and insulin resistance. Thus, the dichotomous changes in HIF-1α transcriptional activity and brown/beige/white fat balance in IH and SH should enable exploration of mechanisms by which altered sympathetic outflow, such as that which occurs in apneic patients, results in whitening, rather than the anticipated browning of adipose tissues that occurs in SH.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 1044-1549eISSN: 1535-4989DOI: 10.1165/rcmb.2016-0243ocTitel-ID: cdi_proquest_miscellaneous_1891850547
- Format
- –
- Schlagworte
- Adenylate Kinase - metabolism, Adipocytes, Adipose Tissue, White - pathology, Angiogenesis, Animals, Autophagy, Autophagy-Related Protein 7 - metabolism, Body fat, Chronic Disease, Experiments, Forkhead Transcription Factors - metabolism, Gene expression, Gene Expression Regulation, Hypoxia, Hypoxia - pathology, Hypoxia-Inducible Factor 1, alpha Subunit - genetics, Inflammation, Insulin resistance, Intra-Abdominal Fat - pathology, Laboratories, Male, Metabolism, Mice, Inbred C57BL, Nitric Oxide Synthase Type III - genetics, Nitric Oxide Synthase Type III - metabolism, Obesity, Oxygen - metabolism, Partial Pressure, Platelet Endothelial Cell Adhesion Molecule-1 - metabolism, RNA, Messenger - genetics, RNA, Messenger - metabolism, Rodents, Sleep, Sleep apnea, Transcription, Genetic, Vascular Endothelial Growth Factor A - genetics, Vascular Endothelial Growth Factor A - metabolism