# The role of gut microbiota in regulating functional diversity of diet-responsive hypothalamic myeloid cells

> **NIH NIH R03** · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · 2020 · $121,125

## Abstract

Summary/Abstract
 Neurons and local CNS-resident immune cells engage in complex interactions to regulate brain function. In
the mediobasal hypothalamus (MBH), a critical integrator of energy balance, diets rich in fat rapidly induce the
inflammatory activation and accumulation of a heterogeneous population of myeloid cells, broadly termed
microglia. We showed that microglia activated in this context are sufficient to stimulate food intake and body
weight gain, however the metabolic factors initiating this response are unknown. The goal of this proposal is to
determine the role of the gut microbiota in regulating the function of MBH myeloid cells. The objective is to identify
specific myeloid populations responsive to gut microbiota-derived signals and determine how they transduce this
response to influence hypothalamic regulation of metabolic function. We will use this information to design novel
myeloid cell-based therapeutic interventions to limit diet-induced obesity and its metabolic consequences. To
reach our objective, we will leverage our expertise in single-cell profiling of MBH myeloid cells to define specific
populations under gut microbial regulation. Diet is a major factor affecting the composition of the gut microbiota,
and diets rich in saturated fat induce unfavorable alterations in the type and numbers of commensal
microorganisms in the gut. These changes may impact MBH myeloid cell function. Our aim is to determine the
contribution of the gut microbiota in determining hypothalamic myeloid responses to dietary saturated fat. The
following sub-aims are proposed: (1) Determine how the interaction between dietary fat composition and gut
microbiota influences hypothalamic myeloid responses; (2) Determine the specific contribution of gut microbiota
on hypothalamic myeloid function. Completing the proposed work will provide novel insights into how the dietary
fat consumption and the gut microbiota interact to regulate the functional diversity of diet-responsive MBH
myeloid cells and the hypothalamic control of energy metabolism.

## Key facts

- **NIH application ID:** 10041604
- **Project number:** 1R03DK125627-01
- **Recipient organization:** UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
- **Principal Investigator:** Martin Valdearcos
- **Activity code:** R03 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $121,125
- **Award type:** 1
- **Project period:** 2020-08-01 → 2022-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10041604

## Citation

> US National Institutes of Health, RePORTER application 10041604, The role of gut microbiota in regulating functional diversity of diet-responsive hypothalamic myeloid cells (1R03DK125627-01). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10041604. Licensed CC0.

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