title: Estrogen improved metabolic syndrome through down-regulation of VEGF and HIF-1α to inhibit hypoxia of periaortic and intra-abdominal fat in ovariectomized female rats.
abstract: Metabolic syndrome (MBS), a cluster of metabolic abnormalities and visceral fat accumulation, increases cardiovascular risks in postmenopausal women. In addition to visceral fat, perivascular adipose tissue has been recently found to play an important role in vascular pathophysiology. Hence, the present study investigates the effects of estrogen on both intra-abdominal fat (visceral fat) and periaortic fat (perivascular fat) accumulation as well as hypoxia in ovariectomized female rats. Female rats were divided into sham operation, ovariectomy and ovariectomy with 17β-estradiol supplementation groups. Twelve weeks later, we found that estrogen improved MBS via reducing body weight gain, the weight of periaortic and intra-abdominal fat, hepatic triglyceride, and total serum cholesterol levels. Estrogen also increased insulin sensitivity through restoring glucose and serum leptin levels. For periaortic fat, western blot showed estrogen inhibited hypoxia by reducing the levels of VEGF and HIF-1α, which is consistent with the results from immunohistochemical staining. The correlation analysis indicated that perivascular fat had a positive correlation with body weight, intra-abdominal fat or serum total cholesterol, but a negative correlation with insulin sensitivity index. For intra-abdominal fat, real-time fluorescent RT-PCR showed estrogen improved fat dysfunction via reducing the levels of relative leptin, MCP-1 but increasing adiponectin mRNA. Estrogen reduced the levels of VEGF and HIF-1α to inhibit hypoxia but restored the levels of PPARγ and Srebp-1c, which are important for lipid capacity function of intra-abdominal fat. These results demonstrated estrogen improved MBS through down-regulating VEGF and HIF-1α to inhibit hypoxia of periaortic and intra-abdominal fat in ovariectomized female rats.
authors.affiliation: Department of Physiology, Zhongshan School of Medicine, Sun Yat-Sen University, 74 Zhongshan Rd 2, Guangzhou 510080, People's Republic of China.
authors.forename: Jinwen
authors.initials: J
authors.lastname: Xu
authors.forename: Qiuling
authors.initials: Q
authors.lastname: Xiang
authors.forename: Guiping
authors.initials: G
authors.lastname: Lin
authors.forename: Xiaodong
authors.initials: X
authors.lastname: Fu
authors.forename: Kewen
authors.initials: K
authors.lastname: Zhou
authors.forename: Ping
authors.initials: P
authors.lastname: Jiang
authors.forename: Shuhui
authors.initials: S
authors.lastname: Zheng
authors.forename: Tinghuai
authors.initials: T
authors.lastname: Wang
mesh_terms: D052242:Adiponectin / Q000235:genetics; D000818:Animals; D001786:Blood Glucose / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects; D018932:Chemokine CCL2 / Q000235:genetics; D002784:Cholesterol / Q000097:blood; D015536:Down-Regulation / Q000187:drug effects; D004967:Estrogens / Q000494:pharmacology*; D005260:Female; D000860:Hypoxia / Q000378:metabolism*; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000378:metabolism*; D007328:Insulin / Q000097:blood; D007333:Insulin Resistance; D050152:Intra-Abdominal Fat / Q000187:drug effects / Q000378:metabolism*; D020738:Leptin / Q000097:blood; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D024821:Metabolic Syndrome / Q000235:genetics / Q000378:metabolism*; D009929:Organ Size / Q000187:drug effects; D010052:Ovariectomy; D047495:PPAR gamma / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D051780:Sterol Regulatory Element Binding Protein 1 / Q000378:metabolism; D014280:Triglycerides / Q000378:metabolism; D014599:Uterus / Q000187:drug effects / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism*
chemical_list: D052242:Adiponectin; D001786:Blood Glucose; D018932:Chemokine CCL2; D004967:Estrogens; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D007328:Insulin; D020738:Leptin; D047495:PPAR gamma; D012333:RNA, Messenger; D051780:Sterol Regulatory Element Binding Protein 1; D014280:Triglycerides; D042461:Vascular Endothelial Growth Factor A; D002784:Cholesterol