# Role of Nutrient Sensing Receptors for the Gut Microbiota in Metabolism

> **NIH VA I01** · JESSE BROWN VA MEDICAL CENTER · 2023 · —

## Abstract

ABSTRACT
Type 2 diabetes (T2D) is one of the most serious medical diseases facing our society, and
understanding the events leading to T2D, specifically the genesis of obesity and insulin
resistance, key components of T2D, is critical. Fiber, which is known to be protective against
T2D, is fermented by gut bacteria, resulting in the synthesis of short chain fatty acids (SCFAs),
predominantly acetate, propionate, and butyrate. This is one of the key proposed mechanisms
that the gut microbiome protects against these metabolic conditions. Importantly, free fatty acid
receptors 2 (FFA2) and -3 (FFA3), which sense and mediate the action of SCFAs, have altered
expression in obesity and insulin resistant states. These receptors are expressed in β cells and
in enteroendocrine (L) cells, where they are suggested to contribute to the secretion of glucagon-
like peptide-1 (GLP-1) regulating β cell function, which collectively contribute to the secretion of
insulin. These receptors, therefore, are primed to mediate the interaction between bacterial
fermentation to SCFAs and hormonal secretion. We propose to use novel genetic knockout (KO)
murine models to dissect how fiber (via SCFA production) mediates metabolic outcomes such as
obesity and insulin resistance where we will explore at the whole body (global, Aim 1) and tissue-
specific level (Aim 2), focused on the enteroinsular axis, and assess the translational component
of these receptors to human tissues (Aim 3). Overall, this study will reveal that a novel SCFA-
sensing mechanism influences host metabolic response to obesogenic challenge.

## Key facts

- **NIH application ID:** 10535442
- **Project number:** 5I01BX003382-06
- **Recipient organization:** JESSE BROWN VA MEDICAL CENTER
- **Principal Investigator:** Brian Thomas Layden
- **Activity code:** I01 (R01, R21, SBIR, etc.)
- **Funding institute:** VA
- **Fiscal year:** 2023
- **Award amount:** —
- **Award type:** 5
- **Project period:** 2017-04-01 → 2025-09-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10535442

## Citation

> US National Institutes of Health, RePORTER application 10535442, Role of Nutrient Sensing Receptors for the Gut Microbiota in Metabolism (5I01BX003382-06). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10535442. Licensed CC0.

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