Obesity is considered as an inflammatory disease. A proposed trigger of the inflammation is hypoxia, which occurs when the enlargement of vascular network is not sufficient to support the expanding adipocytes. Exenatide, a GLP-1 receptor agonist, plays an anti-inflammatory role in obesity, but the mechanisms are poorly understood. The current study investigated the effects of exenatide on inflammation, hypoxia and microcirculation in epididymal fat of high-fat diet induced obese mice. Here, 8-week-old male C57BL/6 mice were randomly divided into 2 groups: NC group (normal control) and HF group (high-fat diet). After 12 weeks diet induction, HF group was further divided into 2 groups: HF group (HF+saline) and HF+EX group (HF+exenatide, 24nmol/kg/day). Compared with NC group, HF group showed significant increases in weight gain and impaired glucose tolerance; serum inflammatory cytokine levels (IL-6, TNF-α, MCP-1) were elevated. Immunohistochemistry staining of F4/80 showed that macrophage infiltration increased in adipose tissue. The mRNA expressions of hypoxia-induced gene (HIF-1a, eNOS) were significantly upregulated. However, laser confocal microscopy showed that capillary density was reduced in HF group. After 4 weeks exenatide treatment, all the obese induced immune disorder (e.g., inflammatory cytokine levels, macrophage infiltration) and hypoxia were significantly ameliorated, leading to an improved energy homeostasis in HF mice when compared with those receiving saline treatment. Proteins levels of PECAM-1 and VEGF-R2 which are indicators of angiogenesis were obviously elevated and capillary density measured by confocal was dramatically increased by exenatide in epididymal fat tissues. As insufficient vasculature may trigger hypoxia and inflammation in obesity, our results indicated that inflammation and hypoxia in obesity could be reversed by GLP-1 potentially via improved angiogenesis and microcirculation in adipose tissue.


F. Xu: None. Z. Chen: None. Y. Xian: None. H.R. Deng: None. W. Xu: None. H. Liang: None. J. Weng: None.

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