title: Adipose tissue hypoxia and low-grade inflammation: a possible mechanism for ethanol-related glucose intolerance?
abstract: The exact mechanism of ethanol's effects on glucose tolerance has not been well determined. The present study focuses for the first time on hypoxia and low-grade inflammation in adipose tissue (AT). In the in vivo experiments, twenty-four male Wistar rats were randomly allocated into control and ethanol feeding groups. Ethanol-treated rats received edible ethanol once a day at a total dosage of 5 g/kg per d, and the controls received distilled water. Ethanol volumes were adjusted every week. At the end of 8 weeks, we carried out an oral glucose tolerance test. Blood and AT were collected for measuring hypoxia-inducible factor-1α (HIF-1α), GLUT1, TNF-α, IL-6, leptin and vascular endothelial growth factor (VEGF). In the in vitro experiments, differentiated OP9 adipocytes were incubated with 100 mm of ethanol for 48 h; the media and cells were then collected for measuring HIF-1α, GLUT1, TNF-α and IL-6. The results showed that long-term ethanol consumption impaired glucose tolerance in rats. Ethanol consumption had little influence on body weight, but both epididymal and perirenal AT were markedly enlarged in the ethanol-treated rats as compared to the controls. Visceral adipose tissue (VAT) had accumulated, and the protein levels of HIF-1α and GLUT1, the indicators of hypoxia in rat epididymal AT and OP9 adipocytes, were elevated. Secondary to the AT hypoxia, the levels of inflammation-related adipokines, such as TNF-α, IL-6, leptin and VEGF, were increased. Based on these findings, we conclude that VAT hypoxia and low-grade inflammation might be a new mechanism in the treatment of ethanol-related diabetes.
authors.affiliation: Department of Endocrinology,Provincial Hospital Affiliated to Shandong University, Shandong Clinical Medical Center of Endocrinology and Metabolism, Institute of Endocrinology and Metabolism, Shandong Academy of Clinical Medicine,324, Jing 5 Road,Jinan,Shandong250021,People's Republic of China.
authors.forename: Zhen
authors.initials: Z
authors.lastname: He
authors.affiliation: Interventional Department, Provincial Hospital Affiliated to Shandong University,324, Jing 5 Road,Jinan,Shandong250021,People's Republic of China.
authors.forename: Min
authors.initials: M
authors.lastname: Li
authors.affiliation: Department of Endocrinology,Provincial Hospital Affiliated to Shandong University, Shandong Clinical Medical Center of Endocrinology and Metabolism, Institute of Endocrinology and Metabolism, Shandong Academy of Clinical Medicine,324, Jing 5 Road,Jinan,Shandong250021,People's Republic of China.
authors.forename: Dongmei
authors.initials: D
authors.lastname: Zheng
authors.affiliation: Department of Endocrinology,Provincial Hospital Affiliated to Shandong University, Shandong Clinical Medical Center of Endocrinology and Metabolism, Institute of Endocrinology and Metabolism, Shandong Academy of Clinical Medicine,324, Jing 5 Road,Jinan,Shandong250021,People's Republic of China.
authors.forename: Qing
authors.initials: Q
authors.lastname: Chen
authors.affiliation: Department of Otorhinolaryngology-Head and Neck Surgery,Institute of Otorhinolaryngology, Provincial Hospital Affiliated to Shandong University,Jinan,Shandong250021,People's Republic of China.
authors.forename: Wenwen
authors.initials: W
authors.lastname: Liu
authors.affiliation: Department of Endocrinology,Provincial Hospital Affiliated to Shandong University, Shandong Clinical Medical Center of Endocrinology and Metabolism, Institute of Endocrinology and Metabolism, Shandong Academy of Clinical Medicine,324, Jing 5 Road,Jinan,Shandong250021,People's Republic of China.
authors.forename: Li
authors.initials: L
authors.lastname: Feng
mesh_terms: D017667:Adipocytes / Q000737:chemistry; D000273:Adipose Tissue / Q000737:chemistry; D000818:Animals; D015687:Cell Hypoxia / Q000187:drug effects*; D002460:Cell Line; D003924:Diabetes Mellitus, Type 2 / Q000209:etiology; D004822:Epididymis; D000431:Ethanol / Q000008:administration & dosage* / Q000633:toxicity; D018149:Glucose Intolerance; D005951:Glucose Tolerance Test; D051272:Glucose Transporter Type 1 / Q000032:analysis; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000032:analysis; D007249:Inflammation / Q000139:chemically induced*; D007333:Insulin Resistance; D015850:Interleukin-6 / Q000032:analysis; D050152:Intra-Abdominal Fat / Q000378:metabolism; D020738:Leptin / Q000032:analysis; D050356:Lipid Metabolism / Q000187:drug effects; D008297:Male; D051379:Mice; D051381:Rats; D017208:Rats, Wistar; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis; D042461:Vascular Endothelial Growth Factor A / Q000032:analysis
chemical_list: D051272:Glucose Transporter Type 1; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D015850:Interleukin-6; D020738:Leptin; C495678:Slc2a1 protein, mouse; C495679:Slc2a1 protein, rat; D014409:Tumor Necrosis Factor-alpha; D042461:Vascular Endothelial Growth Factor A; D000431:Ethanol
keywords: Adipose tissue; Ethanol; Glucose intolerance; Hypoxia; Inflammation