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: Zhen He, Min Li, Dongmei Zheng, Qing Chen, Wenwen Liu, Li Feng
• Journal: The British journal of nutrition (Br J Nutr) Vol. 113 Issue 9 Pg. 1355-64 (May 14 2015) ISSN: 1475-2662 [Electronic] England
• PMID: 25989996 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Glucose Transporter Type 1
• Hypoxia-Inducible Factor 1, alpha Subunit
• Interleukin-6
• Leptin
• Slc2a1 protein, mouse
• Slc2a1 protein, rat
• Tumor Necrosis Factor-alpha
• Vascular Endothelial Growth Factor A
• Ethanol

Topics

• Adipocytes (chemistry)
• Adipose Tissue (chemistry)
• Animals
• Cell Hypoxia (drug effects)
• Cell Line
• Diabetes Mellitus, Type 2 (etiology)
• Epididymis
• Ethanol (administration & dosage, toxicity)
• Glucose Intolerance
• Glucose Tolerance Test
• Glucose Transporter Type 1 (analysis)
• Hypoxia-Inducible Factor 1, alpha Subunit (analysis)
• Inflammation (chemically induced)
• Insulin Resistance
• Interleukin-6 (analysis)
• Intra-Abdominal Fat (metabolism)
• Leptin (analysis)
• Lipid Metabolism (drug effects)
• Male
• Mice
• Rats
• Rats, Wistar
• Tumor Necrosis Factor-alpha (analysis)
• Vascular Endothelial Growth Factor A (analysis)