# Obesity, Metabolic Syndrome, and Lymphatic Dysfunction

> **NIH NIH R56** · UNIVERSITY OF SOUTH FLORIDA · 2022 · $601,172

## Abstract

The relationship between mesenteric lymphatic vessels and surrounding visceral adipose of the mesentery has
received increased attention due to observations that imply that dysfunctional lymphatic vessels contribute to
adipose deposition in the mesentery. While there has been much work done in rodent models of obesity and
metabolic syndrome, there is virtually nothing known about how mesenteric lymphatic vessels are altered both
structurally and functionally in humans with metabolic syndrome. To address this important and enormous
knowledge gap, novel protocols to study human mesentery and lymphatic vessels derived from organ donors
with or without metabolic syndrome have been developed and optimized. The rationale for this approach is that
the findings will enable a leap forward in knowledge about the lymphatic-visceral adipose axis that is directly
relevant to humans. The central hypothesis to be tested is that metabolic syndrome impairs lymphatic function
and that impaired mesenteric lymphatics perpetuate metabolic dysfunction. Guided by robust preliminary data,
this hypothesis will be tested in with two specific aims. Specific Aim 1 is to determine mechanisms underlying
lymphatic dysfunction in obesity and metabolic syndrome. Specific Aim 2 is to determine how dysfunctional
lymphatics contribute to metabolic deficits in mesenteric tissue. These aims will utilize mesenteric tissue from
human organ donors, which permits the study of mesenteric lymphatic pump function, permeability, and network
structure. The functional studies will be coupled to transcriptomic and proteomic approaches to identify the RNA
and protein landscapes in the mesenteric adipose depots surrounding lymphatic vessels. In addition, studies of
in vivo lymphatic pumping and permeability in relevant rat and mouse models will help identify causal
mechanisms in the two-way communication between lymphatic vessels and visceral adipose tissue. The
significance of the proposed research is that it will provide the first comprehensive analysis of human mesentery,
including the protein and RNA landscapes, lymphatic vessel networks, lymphatic pump function, and lymphatic
permeability that will produce novel information about how human lymphatic vessels interact with visceral
adipose tissue in the context of metabolic syndrome. The proposed research is innovative because it opens a
new line of investigation focusing on human mesenteric lymphatic structure and function that will provide the first
large-scale evaluation of human mesenteric lymphatic pump function and permeability directly related to human
health and disease.

## Key facts

- **NIH application ID:** 10705331
- **Project number:** 1R56HL153542-01A1
- **Recipient organization:** UNIVERSITY OF SOUTH FLORIDA
- **Principal Investigator:** JEROME W BRESLIN
- **Activity code:** R56 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $601,172
- **Award type:** 1
- **Project period:** 2022-09-22 → 2024-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10705331

## Citation

> US National Institutes of Health, RePORTER application 10705331, Obesity, Metabolic Syndrome, and Lymphatic Dysfunction (1R56HL153542-01A1). Retrieved via AI Analytics 2026-05-21 from https://api.ai-analytics.org/grant/nih/10705331. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*