# Role of the GI lymphatic system in hormonal signaling and nutrient metabolism

> **NIH NIH R01** · UNIVERSITY OF CINCINNATI · 2021 · $593,943

## Abstract

Project Summary
 While the physiological importance of lymph chylomicron transport is well-documented, the
physiological roles of other lymph factors remain poorly understood. This is a critical area for additional new
research, as indicated in the RFA, which requests that applications determine “how the signals lymphatics are
receiving may affect their function and, thus overall intestinal function”. In order to study these relationships, we
will use the rat lymph-fistula model, a novel and powerful paradigm that is routine in our lab, to study the
secretion of hormones and other GI factors in vivo. Using this paradigm, we initially demonstrated that
lymphatic concentrations of incretin hormones (GLP-1, GIP) are markedly higher than those in the portal or
systemic circulation. Our new preliminary data indicate the intriguing possibility that the lymph also transports
locally-produced glucocorticoid hormones in response to dietary lipids, and that the lymphatic transport of
dietary lipids and hormones varies in a sex- and/or estrous cycle-dependent manner. The present proposal
addresses the overall hypothesis that the transport and signaling of hormones and related factors within the GI
lymphatic system is necessary for normal functioning of the GI tract and for overall metabolic health. Aim 1
determines the physiological relevance of high incretin concentrations in intestinal lymph. We assess the
impact of lymph diversion on glucose absorption and distribution, and determine the mechanisms by which the
stomach regulates incretin secretion during nutrient ingestion. Aim 2 determines the physiological relevance of
nutrient-induced glucocorticoid hormones in intestinal lymph. We identify the source of the lymphatic
glucocorticoid response to lipids, and determine the extent that lymphatic glucocorticoids regulate lipid
absorption and its associated proinflammatory response. Aim 3 determines the role of sex and the estrous
cycle in intestinal lymph physiology. We evaluate the extent that lymphatic transport functions (for
chylomicrons, incretins, inflammatory mediators, and glucocorticoids) vary with sex and/or the estrous cycle,
and test the mechanistic role of ovarian hormones in these processes. This multi-PI proposal leverages the
complementary expertise of a highly collaborative team that includes Dr. Patrick Tso (expert in GI lymphatics
and metabolic hormones), Dr. Yvonne Ulrich-Lai (expert in the HPA axis and corticosterone signaling), and Dr.
Min Liu (expert in ovarian hormone signaling and energy balance).

## Key facts

- **NIH application ID:** 10164765
- **Project number:** 5R01DK119135-04
- **Recipient organization:** UNIVERSITY OF CINCINNATI
- **Principal Investigator:** Min Liu
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $593,943
- **Award type:** 5
- **Project period:** 2018-09-20 → 2023-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10164765

## Citation

> US National Institutes of Health, RePORTER application 10164765, Role of the GI lymphatic system in hormonal signaling and nutrient metabolism (5R01DK119135-04). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10164765. Licensed CC0.

---

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