# Adipose tissue distribution determines microglial regulation of hippocampal plasticity

> **NIH NIH R01** · AUGUSTA UNIVERSITY · 2024 · $392,018

## Abstract

PROJECT SUMMARY
The ‘apple-shaped’ anatomical pattern that accompanies visceral adiposity increases dementia risk in humans,
but the 'pear-shaped' distribution that reflects subcutaneous adiposity does not predict cognitive impairment and
may be protective. Several recent studies, including from our lab, have outlined signaling cascades linking
peripheral and central inflammation in obesity in males, but vulnerability to obesity-induced metabolic pathology
is sexually dimorphic, and susceptibility to neuroinflammation follows similar patterns. Adult females exhibit
stronger innate immunity, and evidence from clinical and experimental studies suggests that this dimorphism
involves sex differences in anti-inflammatory cytokines. However, current understanding of tissue-specific anti-
inflammatory signaling remains rudimentary due to the scarcity of approaches for selective manipulation.
Moreover, regionally heterogeneous responses to dietary obesity in different brain areas remain incompletely
characterized, leaving open questions surrounding feedforward neuroimmune control versus immunological
feedback. The proposed experiments will generate a comprehensive topographical map of neuroimmune
responses to chronic overnutrition and elucidate the role of the anti-inflammatory cytokine interleukin-4 in these
effects. We will use light-inducible cre drivers and direct delivery of tamoxifen metabolites to selectively
manipulate immune cells in cerebrospinal fluid. These technically innovative approaches will be followed by
anatomical mapping of lymphocytes and myeloid cells in cleared tissues, single-cell flow cytometric analysis, or
analysis of neuronal function at the behavioral and electrophysiological level. Understanding circuit-specific
sexual dimorphisms in obesity could yield fundamental insights into the pathogenesis of neuroinflammation in
different microenvironments, and could also identify target structures for noninvasive therapeutic modulation.

## Key facts

- **NIH application ID:** 10827056
- **Project number:** 2R01DK110586-06A1
- **Recipient organization:** AUGUSTA UNIVERSITY
- **Principal Investigator:** Alexis M. Stranahan
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $392,018
- **Award type:** 2
- **Project period:** 2017-07-01 → 2028-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10827056

## Citation

> US National Institutes of Health, RePORTER application 10827056, Adipose tissue distribution determines microglial regulation of hippocampal plasticity (2R01DK110586-06A1). Retrieved via AI Analytics 2026-05-27 from https://api.ai-analytics.org/grant/nih/10827056. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*