Exenatide mitigates inflammation and hypoxia along with improved angiogenesis in obese fat tissue

Abstract

Obesity-associated chronic inflammation in adipose tissue is par tly attributed to hypoxia with insufficient microcirculation. Previous studies have shown t hat exenatide, a glucagon-like peptide 1 (GLP-1) receptor agonist, plays an anti -inflammatory role. Here, we investigate its effects on inflammation, hypoxia and microcirc ulation in white adipose tissue of diet-induced obese (DIO) mice. DIO mice were injected intraperitoneally with exenatide or normal saline for 4 weeks, while mice on chow diet were used as normal controls. The mRNA and protein levels of pro-inflammat ory cytokines, hypoxia-induced genes and angiogenic factors were detected. Cap illary density was measured by laser confocal microscopy and immunochemistry stain ing. After 4-week exenatide administration, the dramatically elevated pro-inflammatory cytokines in serum and adipose tissue and macrophage infiltration in adipose tissue of DIO mice were significantly reduced. Exenatide also ameliorated expressions of hypoxia-related genes in obese fat tissue. Protein levels of endothelial marker s and pro-angiogenic factors including vascular endothelial growth factor and its re ceptor 2 were augmented in accordance with increased capillary density by exenatide in DIO mice. Our results indicate that inflammation and hypoxia in adipose tissue can be mitigated by GLP-1 receptor agonist potentially via improved angiogenesis and micr ocirculation in obesity.