# Internal State Sensing Via The Gut-Brain Axis

> **NIH NIH R01** · SCRIPPS RESEARCH INSTITUTE, THE · 2020 · $509,603

## Abstract

PROJECT SUMMARY
Metabolic dysregulation is a central node underlying many age-dependent diseases including diabetes,
cardiovascular disease, cancer and neurodegeneration, and more generally, is thought to accelerate the aging
process. Two organ systems decode sensory information to control energy metabolism throughout the body:
the central nervous system, and the gut. How we regulate our metabolism and the interplay between the brain
and the gut in this process are major unanswered questions in biology and medicine. The long-term goal of my
laboratory is to understand mechanisms of neuroendocrine communication between the brain and the gut, and
the defects in this process that lead to diseases of energy dysregulation. We use the C. elegans model for our
work, a tremendously useful system to map energy balance circuits and visualize the gut-brain axis in living
animals. My lab has identified a neuronal circuit in the brain that integrates sensory information from the
environment, and drives systemic fat loss via a tachykinin brain-to-gut signaling pathway. In a surprising twist,
we find that intestinal fat status modulates the tachykinin-secreting neurons in this circuit, suggesting that
internal nutrient state information is relayed directly from the gut, back to the brain. A genetic screen for
interoceptive molecules revealed two peptides: INS-7, a member of the insulin/relaxin superfamily, and NLP-7,
a member of the cholecystokinin/gastrin family. Our central hypothesis is that gut-brain peptides relay internal
state information from the intestine to tune neuronal responses and control the extent to which the nervous
system is able to modulate whole-body metabolism and behavior. Aim 1. Decoding the effects of gut signals on
sensory neurons that control body fat. We will elucidate the molecular mechanisms by which INS-7 signaling
modifies sensory neuron properties to alter whole-body metabolism. Aim 2. Defining gut-to-brain signals
underlying internal state-dependent food-seeking behavior. We will identify mechanisms by which NLP-7 from
the gut regulates food-seeking and provide a functional map of gut-responsive interoceptive neurons. Aim 3.
Deciphering mechanisms by which gut sensory and metabolic functions are coupled to enteroendocrine
secretions. We have developed methodologies to visualize and quantify secreted peptides in living animals.
We will harness this capability to conduct a genetic screen and define the molecular pathways by which the
sensing of internal nutrient and fat status regulates the release of gut endocrine peptides. The objective of this
application is to decode the molecular and endocrine mechanisms by which interoceptive information from the
gut is integrated into the neuronal sensory circuits, and how it influences lipid metabolism and food-seeking
behavior. In so doing, we will define the core cellular and molecular components of the gut-brain axis. Other
expected outcomes are that we will provide the first sensory a...

## Key facts

- **NIH application ID:** 10120465
- **Project number:** 1R01DK124706-01A1
- **Recipient organization:** SCRIPPS RESEARCH INSTITUTE, THE
- **Principal Investigator:** Supriya Srinivasan
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $509,603
- **Award type:** 1
- **Project period:** 2020-09-24 → 2024-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10120465

## Citation

> US National Institutes of Health, RePORTER application 10120465, Internal State Sensing Via The Gut-Brain Axis (1R01DK124706-01A1). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10120465. Licensed CC0.

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