# The Role of Lipocalin 2 in Cancer Cachexia

> **NIH NIH F30** · OREGON HEALTH & SCIENCE UNIVERSITY · 2020 · $49,444

## Abstract

Project Summary
Illness behaviors, metabolic disturbances, and cognitive injury are common in cancer patients and frequently
lead to wasting or cachexia. This devastating state of malnutrition is brought about by a synergistic combination
of decreased appetite and increase in metabolism of fat and lean body mass. The severity of cachexia is often
the primary determining factor in both quality of life and ultimate survival. There are currently no effective
treatments for cachexia, and its mechanisms are poorly understood. Our lab has previously elucidated the
actions of inflammatory cytokines on hypothalamic neurons and their roles in driving cachexia symptoms.
Cytokines are produced in the hypothalamus during systemic inflammatory states, and cerebral injection of IL-
1B or TNF-alpha recapitulate the signs and symptoms of cachexia. However, chronic administration of these
cytokines results in desensitization and loss of cachexia symptoms, demonstrating canonical inflammatory
cytokines alone are insufficient for sustaining cachexia. Thus, the molecular pathways responsible for driving
chronic central nervous system (CNS) inflammation and cachexia symptoms remain unknown.
 Lipocalin 2 (LCN2) is a secreted protein produced during numerous acute and chronic diseases, yet its
role in cachexia is unexplored. LCN2 is an important mediator of inflammation and is able to access appetite-
regulating brain regions found near circumventricular structures. I found that, in several murine models of
pancreatic ductal adenocarcinoma (PDAC)-associated cachexia, LCN2 is robustly upregulated in the circulation
and brain. Chronic central administration of LCN2 results in appetite suppression and neuron stress that does
not desensitize. Lastly, LCN2 knockout mice are robustly protected from cachexia-anorexia, fatigue, and lean
mass loss. I hypothesize that the sustained production of LCN2 by brain endothelium drives appetite
suppression, hypothalamic dysfunction, and neurocognitive injury during cancer cachexia. This project proposes
to first assess the differential contribution of circulating versus CNS-derived LCN2 in driving cachexia symptoms.
It will then determine if LCN2 is sufficient to produce symptoms of cachexia, including anorexia, fatigue,
depression, and cognitive injury. Finally, this project will explore novel receptor-mediated mechanisms by which
LCN2 induces neuron stress.
 Collectively, achieving the goals of the proposal will: 1) enhance our understanding of the root cause of
cachexia, 2) provide novel therapeutic targets and strategies for treating appetite dysregulation and cognitive
injury during cachexia, and 3) describe a novel mechanism by which LCN2 mediates neuronal stress that is
broadly applicable to several chronic diseases.

## Key facts

- **NIH application ID:** 9991476
- **Project number:** 1F30CA254033-01
- **Recipient organization:** OREGON HEALTH & SCIENCE UNIVERSITY
- **Principal Investigator:** Brennan Glenn Olson
- **Activity code:** F30 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $49,444
- **Award type:** 1
- **Project period:** 2020-07-30 → 2025-07-29

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9991476

## Citation

> US National Institutes of Health, RePORTER application 9991476, The Role of Lipocalin 2 in Cancer Cachexia (1F30CA254033-01). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/9991476. Licensed CC0.

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