# Integrative Physiology of Obesity: Role of GPR160

> **NIH NIH R01** · SAINT LOUIS UNIVERSITY · 2020 · $504,332

## Abstract

PROJECT SUMMARY/ABSTRACT
Peptide neurotransmitters play important roles in the neuronal networks regulating appetite in several brain
regions, including brainstem feeding centers such as the nucleus tractus solitarius (NTS) and hypothalamus.
One such peptide, cocaine- and amphetamine-regulated transcript (CART), appears to act as a downstream
mediator integrating peripheral metabolic signals including glucagon like peptide 1 and cholesytokinin. Central
injection of CART inhibits food intake in multiple animal models and global deletion of CART leads to
exaggerated food intake and increased susceptibility to a high fat diet in mice. Additionally, central CART
neurons appear to play a role in whole body glucose homeostasis and meal patterning. To date, the identity of
the CART receptor(s) has remained elusive, thus limiting the therapeutic potential of CART analogs for the
treatment of obesity and associated eating disorders. CART activates downstream signaling cascades typical
of those associated with G protein coupled receptors (GPCRs). Using our unique Deductive Reasoning
Ligand-Receptor matching strategy, we identified the orphan GPCR, GPR160, to be a receptor for CART. In
this Research Plan, we propose to test the overall hypotheses that activation of GPR160 is necessary for the
biologic effect of CART peptides and that endogenous GPR160 plays a significant role in the regulation of
appetite and metabolic function. We will test these hypotheses in four Specific Aims using a combination of
cutting edge molecular techniques and innovative animal models.
S.A. 1: Examine the functional and physical relationship between CART and GPR160.
S.A. 2: Investigate the role of endogenous GPR160 in the short-term regulation of
appetite and metabolism.
S.A. 3: Investigate the role of endogenous GPR160 in the hypothalamic regulation of appetite and stress
hormone secretion.
S.A. 4: Establish a genetic model of GPR160 absence to investigate the importance of the
receptor in the long term regulation of metabolic function.
The proposed studies will further evaluate the functional and physical relationship between GPR160 and
CART, establish CART and GPR160 as an important ligand-receptor pair in the short term and long term
regulation of metabolic function, and produce innovative research tools, such as the GPR160-flox rat.

## Key facts

- **NIH application ID:** 9984344
- **Project number:** 5R01DK118340-03
- **Recipient organization:** SAINT LOUIS UNIVERSITY
- **Principal Investigator:** Gina L.C. Yosten
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $504,332
- **Award type:** 5
- **Project period:** 2018-09-14 → 2023-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9984344

## Citation

> US National Institutes of Health, RePORTER application 9984344, Integrative Physiology of Obesity: Role of GPR160 (5R01DK118340-03). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9984344. Licensed CC0.

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