Abstract
In the last issue of Lymphatic Research and Biology, we had the opportunity to feature an original investigation of the gut–lymph concept.1,2 In this issue of the journal, we have the opportunity to further highlight the link between the respective functions of the gut and the lymphatic circulatory apparatus.
The featured original investigation by Creed et al. provides an opportunity to explore a preclinical model that simulates the effect of generalized lymphatic anomaly (GLA). This and other developmental anomalies of the lymphatic vasculature, although uncommon, pose substantial challenges to the treating clinician; among these, the problem of recurrent chylous effusions (chylothorax and chylous ascites) is commonly encountered.3,4 Although it is common clinical practice to limit dietary fat in these patients, in the current preclinical investigation, the authors sought to explore the hypothesis that dietary fatty acid composition can influence the potential for lymphatic vascular dysfunction and subsequent chylous effusion.
For their study, the authors utilized VEGF-D overexpressed to simulate GLA. Murine subjects were assigned, respectively, to mixed high-fat diet (HFD), high saturated fat diet (HSFD), or high unsaturated fat diet. Oral triglyceride uptake and mesenteric fat were analyzed. The lymphatic vascular consequences were assessed through whole mount immunofluorescence and gene expression profiling, and body composition was assessed by magnetic resonance imaging.
When compared with control animals, those fed HSFD experienced increases in TNF-α, IL-6, and IL-10 expression. The incidence of chylous accumulation in the mice fed a mixed HFD.
This is a novel and interesting investigation that sheds mechanistic light on a problem with very direct clinical consequences. Further exploration of preclinical models such as this one will ideally provide clinicians with the dietary tools to best manage these very challenging patients.