Adipose tissue hypoxia and low-grade inflammation: a possible mechanism for ethanol-related glucose intolerance?
作者
He, Z;Li, M;Zheng, DM;Chen, Q;Liu, WW;Feng, L
作者单位
[He, Zhen; Zheng, Dongmei; Chen, Qing; Feng, Li] Shandong Acad Clin Med, Prov Hosp, Shandong Clin Med Ctr Endocrinol & Metab, Inst Endocrinol & Metab,Dept Endocrinol, Jinan 250021, Shandong, Peoples R China.;-;[Li, Min] Shandong Acad Clin Med, Prov Hosp, Intervent Dept, Jinan 250021, Shandong, Peoples R China.;-;[Liu, Wenwen] Shandong Acad Clin Med, Prov Hosp, Inst Otorhinolaryngol, Dept Otorhinolaryngol Head & Neck Surg, Jinan 250021, Shandong, Peoples R China.
摘要
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 5g/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-1 alpha (HIF-1 alpha), GLUT1, TNF-alpha, IL-6, leptin and vascular endothelial growth factor (VEGF). In the in vitro experiments, differentiated OP9 adipocytes were incubated with 100mm of ethanol for 48h; the media and cells were then collected for measuring HIF-1 alpha, GLUT1, TNF-alpha 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-1 alpha 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-alpha, 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.
关键词
TUMOR-NECROSIS-FACTOR; BODY-MASS INDEX; NF-KAPPA-B; INSULIN-RESISTANCE; ALCOHOL-CONSUMPTION; METABOLIC SYNDROME; ABDOMINAL OBESITY; DIABETES-MELLITUS; ENDOCRINE ORGAN; RISK-FACTORS
基本信息
