# Illuminating the Metabolic Function of GPR162 by Delineating Downstream Signaling Pathways and Characterizing Hypothalamic Expression Pattern

> **NIH NIH R03** · INDIANA UNIVERSITY INDIANAPOLIS · 2020 · $171,642

## Abstract

PROJECT SUMMARY
Of the twenty thousand proteins encoded in the human genome, three thousand of them are considered as part
of the `druggable genome' by their estimated capability to bind drug-like molecules. Ion channels, kinases and
G protein-coupled receptors (GCPRs) are three important components of the `druggable genome'. GPCRs are
the most successful class of druggable targets. Currently, GPCRs are the target of over ~26% of the Food and
Drug Administration (FDA) approved drugs. GPCRs are a family of seven-transmembrane (7TM) receptors that
regulate important physiological functions through a diverse array of the endogenous ligands, which include light,
odor, neurotransmitter, ion, hormone, peptide, lipid, metabolite, etc. Yet, despite of their functional importance
and excellent druggability, a large number of non-olfactory GPCRs are still understudied, which is largely due to
the unknown nature of the endogenous ligands and physiological functions. Therefore, there is an urgent need
to characterize the understudies GPCRs by providing new research tools and characterize the physiological
function of these receptors. Metabolic diseases, including diabetes and obesity, have become a major health
problem worldwide. Sedentary lifestyles and the abundance of palatable and calorie-dense foods in modern
societies have undoubtedly contributed to the increasing prevalence of obesity, which is associated with the
incidence of multiple co-morbidities including diabetes and cardiovascular diseases. The brain is a key regulator
for energy balance, owing to its ability to sense nutrients, control reward/motivation behavior, and orchestrate
peripheral responses. The overarching goal of our research program is to understand the molecular mechanisms
of neurohormonal pathways critical for feeding and glucose metabolism. Specifically, we aim to focus on the
understudied GPCRs in the neuroendocrine system and study their roles in the pathophysiology of obesity and
diabetes. Our preliminary study showed that GPR162 expression in the hypothalamus is regulated by feeding
conditions and correlated with metabolic derangements. Our data, together with data from the public domain,
strongly suggest that more investigations are needed to understand the upstream signals and downstream
activities of this understudied GPCR and its relevance to metabolic disease pathophysiology. By characterizing
the tissue / cell expression and the signaling properties of this GPCR, we will establish key background
knowledge that is necessary to develop developing screening assays and performing pilot screening to obtain
agonist and antagonist for GPR162. Moreover, the results from this work will have the potential to translate to
humans and to the development of novel therapeutic reagents for metabolic diseases. This complementary
expertise of the investigators in GPCR biology and metabolism and the on-going collaboration support the
feasibility and increase the likelihood of success. Su...

## Key facts

- **NIH application ID:** 10046905
- **Project number:** 1R03TR003350-01
- **Recipient organization:** INDIANA UNIVERSITY INDIANAPOLIS
- **Principal Investigator:** Hongxia Ren
- **Activity code:** R03 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $171,642
- **Award type:** 1
- **Project period:** 2020-09-01 → 2023-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10046905

## Citation

> US National Institutes of Health, RePORTER application 10046905, Illuminating the Metabolic Function of GPR162 by Delineating Downstream Signaling Pathways and Characterizing Hypothalamic Expression Pattern (1R03TR003350-01). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10046905. Licensed CC0.

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