# Short Chain Fatty Acids (SCFAs) and SCFA G-protein Coupled Receptors in Hypertension

> **NIH NIH R56** · JOHNS HOPKINS UNIVERSITY · 2021 · $100,000

## Abstract

Project Summary
Metabolites produced by the gut microbiota play critical roles in host physiology and
pathophysiology. We have previously shown that one class of microbial metabolites, short
chain fatty acids (SCFAs), bind to host G protein-coupled receptors (GPCRs) to modulate blood
pressure. We have found that SCFAs activate Olfactory Receptor 78 (Olfr78) to modulate renin
release, and activate Gpr41 to modulate vascular tone. Recently, we have identified two other
GPCRs (Gpr43 and Olfr558) which respond to SCFAs and are expressed in the vasculature,
and thus are well-positioned to also influence blood pressure. In this proposal, we Aim to
investigate how SCFA-GPCR signaling pathways modulate – and are modulated by –
hypertension. In Specific Aim 1, we will examine how components of the SCFA signaling
pathway (SCFAs, as well as SCFA GPCRs) are modulated in two different models of
hypertension (Angiotensin II, and DOCA/Salt). Plasma SCFAs increase in hypertension; here,
we will test our novel hypothesis that altered host handling of SCFAs, not increased microbial
production, is key in determining plasma levels. To achieve this, we will measure microbial
production, intestinal reabsorption, and renal clearance of SCFAs in normotension and in two
hypertension models. To examine SCFA GPCRs in hypertension, we will determine how the
expression of Olfr78, Olfr558, Gpr41, and Gpr43 is altered in normotension versus
hypertension. In Specific Aim 2 of this proposal, we will determine how each of these
components of the SCFA-GPCR signaling pathway can modulate the course of hypertension.
We have extensively studied Olfr78 and Gpr41 in the past, therefore, we will focus on
uncovering novel roles for Olfr558 and Gpr43 in blood pressure regulation under basal
conditions and in hypertension. In a separate experiment, we will test our novel hypothesis that
low doses of SCFAs are protective but higher doses of SCFAs are detrimental, thereby
resolving a conflict in the literature. To do this, we will treat normotensive and hypertensive
mice with varying doses of exogenous SCFAs. In sum, these studies will advance the field by
illuminating how SCFAs and SCFA GPCRs are modulated in hypertension, and by determining
how modulation of this pathway can alter the course of hypertension.

## Key facts

- **NIH application ID:** 10476066
- **Project number:** 2R56DK107726-06A1
- **Recipient organization:** JOHNS HOPKINS UNIVERSITY
- **Principal Investigator:** Jennifer L Pluznick
- **Activity code:** R56 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $100,000
- **Award type:** 2
- **Project period:** 2015-12-01 → 2022-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10476066

## Citation

> US National Institutes of Health, RePORTER application 10476066, Short Chain Fatty Acids (SCFAs) and SCFA G-protein Coupled Receptors in Hypertension (2R56DK107726-06A1). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10476066. Licensed CC0.

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