Adipose tissue hypoxia and low-grade inflammation: a possible mechanism for ethanol-related glucose intolerance?
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.
['He|Zhen|Z|', 'Li|Min|M|', 'Zheng|Dongmei|D|', 'Chen|Qing|Q|', 'Liu|Wenwen|W|', 'Feng|Li|L|']
D017667:Adipocytes D000273:Adipose Tissue D000818:Animals D015687:Cell Hypoxia D002460:Cell Line D003924:Diabetes Mellitus, Type 2 D004822:Epididymis D000431:Ethanol D018149:Glucose Intolerance D005951:Glucose Tolerance Test D051272:Glucose Transporter Type 1 D051795:Hypoxia-Inducible Factor 1, alpha Subunit D007249:Inflammation D007333:Insulin Resistance D015850:Interleukin-6 D050152:Intra-Abdominal Fat D020738:Leptin D050356:Lipid Metabolism D008297:Male D051379:Mice D051381:Rats D017208:Rats, Wistar D014409:Tumor Necrosis Factor-alpha D042461:Vascular Endothelial Growth Factor A
Adipose tissue Hypoxia Inflammation Glucose intolerance Ethanol