Improving high-fat diet-induced obesity and fatty liver by adipose tissue targeted delivery of vascular endothelial growth factor-B

Life Sci. 2020 Jul 15:253:117677. doi: 10.1016/j.lfs.2020.117677. Epub 2020 Apr 17.

Abstract

Impaired vascularization of adipose tissue leads to local hypoxia and results in chronic inflammation and obesity-related metabolic disorders. We have recently constructed an engineered protein named tPep-VEGF-B by bridging vascular endothelial growth factor (VEGF-B) with an adipose-targeted peptide. Here, we reported tPep-VEGF-B diminishes obesity and alleviates metabolic syndrome. High fat diet (HFD) treated mice had reduced adipose vascular density and showed adipose hypoxia and metabolic complications. In contrast, the treatment of tPep-VEGF-B repressed HFD-induced body weight gain, which led to increased adipose vasculature and reduced hypoxia. This treatment also alleviated obesity associated hyperlipidemia and fatty liver disease. This study provided a leading molecule for the treatment of type 2 diabetes and other metabolic diseases. It also provided experimental support for the theory that modulation of angiogenesis plays a key role in the treatment of metabolic diseases.

Keywords: Adipose tissue; Angiogenesis; Hypoxia; Obesity; VEGF-B.

MeSH terms

  • Adipose Tissue / blood supply*
  • Animals
  • Diet, High-Fat / adverse effects
  • Disease Models, Animal
  • Drug Delivery Systems*
  • Fatty Liver / prevention & control*
  • Hyperlipidemias / prevention & control
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Obesity / prevention & control*
  • Peptides / chemistry
  • Vascular Endothelial Growth Factor B / administration & dosage*
  • Vascular Endothelial Growth Factor B / pharmacology

Substances

  • Peptides
  • Vascular Endothelial Growth Factor B