Characterizing Lymphangiogenesis and Concurrent Inflammation in Adipose Tissue in Response to VEGF-D | Academic Article individual record
abstract

The metabolic consequences of obesity arise from local inflammation within expanding adipose tissue. In pre-clinical studies targeting various inflammatory factors, systemic metabolism can be improved through reduced adipose inflammation. Lymphatic vessels are a critical regulator of inflammation through roles in fluid and macromolecule transport and immune cell trafficking and immunomodulation. Lymphangiogenesis, the expansion of the lymphatic network, is often a necessary step in restoring tissue homeostasis. Using Adipo-VD mice, a model of adipocyte-specific, inducible overexpression of the potent lymphangiogenic factor vascular endothelial growth factor-D (VEGF-D), we previously identified that dense de novo adipose lymphatics reduced immune accumulation and improved glucose homeostasis in obesity. On chow diet, however, Adipo-VD mice demonstrated increased adipose tissue immune cells, fibrosis, and inflammation. Here, we characterize the time course of resident macrophage accumulation and lymphangiogenesis in male and female Adipo-VD mice fed chow and high fat diets, examining multiple adipose depots over 4 months. We find that macrophage infiltration occurs early, but resolves with concurrent lymphatic expansion that begins robustly after 1 month of VEGF-D overexpression in white adipose tissue. In obesity, female Adipo-VD mice exhibit reduced lymphangiogenesis and maintain a more glycolytic metabolism compared to Adipo-VD males and their littermates. Adipose lymphatic structures appear to expand by a lymphvasculogenic mechanism involving lymphatic endothelial cell proliferation and organization with a cell source we that failed to identify; hematopoietic cells afford minimal structural contribution. While a net positive effect occurs in Adipo-VD mice, adipose tissue lymphangiogenesis demonstrates a dichotomous, and time-dependent, inflammatory tissue remodeling response.

author list (cited authors)
Chakraborty, A., Scogin, C. K., Rizwan, K., Morley, T. S., & Rutkowski, J. M.
publication date
2020
publisher
published in
keywords
  • VEGFR-3
  • Vegf-d
  • Lymphangiogenesis
  • Lymphatic
  • Metabolic Syndrome
  • Obesity