Lymphatic Wall Remodeling with Systemic and Tissue‐Associated Inflammation in Obese Zucker Rats

Abstract

Lymphatic vessels have an intimate relationship with adipose tissue, and a growing number of reports tie dysfunction of lymphatics to obesity. A large gap currently exists in the knowledge of the pathophysiological mechanisms involved in obesity‐induced lymphatic dysfunction. The goal of this study was to investigate the extent to which obesity gives rise to inflammation and remodeling of the wall of rat mesenteric collecting lymphatic vessels. ZUCKER‐Leprafa (obese) and ZUCKER‐Leprafa/+ (lean) male and/or female rats, in conformance with the FASEB Statement of Principles for the use of Animals in Research and Education, were used for this study. Age groups included 8, 12 and 26–32 wks. Collecting lymphatic vessels were isolated from the mesentery and were mounted onto resistance‐matched glass micropipettes to determine passive wall mechanics. These experiments were performed in a 37°C albumin physiological salt solution (APSS without Ca2+) bath with luminal pressure stepped from 1–5 cm H2O. In addition, mesenteric arcades with adipose tissue and collecting lymphatics were dissected, fixed in 4% paraformaldehyde, processed and embedded in paraffin for sectioning and immunostaining with antibodies to rat‐specific CD68 (macrophage marker) and caveolin‐1 (adipocyte marker) for the quantification of crown‐like structures (CLSs). Blood (serum) and peri‐lymphatic adipose tissue (PLAT) were also collected and analyzed with the currently available panel of 67 inflammatory biomarkers through the Rat Biomarker Testing Service by RayBiotech. The results show that lymphatic wall thickness is significantly greater in obese Zucker rats compared to age‐matched counterparts. Wall:lumin ratio (X100) and medial cross‐sectional area were also significantly greater in obese versus lean male rats at all ages. Many CLSs were observed surrounding mesenteric collecting lymphatics isolated from obese male 12 and 26–32 wk rats. Additionally, CLSs significantly increased with age. In an analyses of serum biomarkers obtained from 12‐wk old lean and obese, male and female rats, we observed that many of the markers in PLAT (IL‐6, IL‐13, adiponectin) and in serum (GM‐CSF, IL‐4, Gas1) were differentially regulated by obesity and sex. The data support the concept that obesity causes an inflammatory environment in the mesentery that is associated with lymphatic vessel wall remodeling and changes to passive wall mechanics. The data also show significant differences in the profiles of inflammatory mediators increased by obesity in male and female Zucker rats, highlighting the importance of studying both sexes.Support or Funding InformationSupported by NIH L40HL097863This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.