# Adipose Tissue Inflammation in Influenza Infection Severity

> **NIH NIH F31** · CINCINNATI CHILDRENS HOSP MED CTR · 2022 · $41,163

## Abstract

ABSTRACT
The obesity pandemic continues unabated, afflicting >500 million people worldwide. Epidemiological evidence
establishes obesity as an independent risk factor for increased susceptibility and severity to Influenza infection.
Altered immune cell function (e.g. cytokine production) is often perceived as a key causative factor for increased
lung tissue damage. However, the contribution of adipocytes, the dominantly altered cell type in obesity with
immune-like properties, to Influenza pathogenesis remains largely ignored. Notably, obesity promotes adipocyte
skewing towards a proinflammatory state and amplifies their immune-like contribution. Here we propose to
examine the contribution of adipocyte inflammatory capacity to influenza disease pathogenesis. Our novel
preliminary data strongly suggest that influenza-induced type I interferon (IFN) sensing skews adipocyte-specific
inflammatory capacity, and promotes systemic and tissue inflammation that correlates with disproportionate lung
tissue damage in mice. Our preliminary findings indicate that: Obese mice infected with influenza, compared to
lean controls, exhibit: (a) increased mortality; (b) more severe lung tissue pathology; (c) increased lung edema;
and (d) elevated lung IL-6 levels. Further, we show that influenza infection: (e) directly shapes white adipose
tissue (WAT) immune cell infiltration and increases WAT type I IFN/IFNAR axis activation; and (f) induces
adipocyte IL-6 inflammatory responses. Lastly, we show that: (g) obesity amplifies adipocyte inflammatory vigor
via the type I IFN/IFNAR axis; (h) adipocytes contribute to systemic inflammatory cytokine production; and (i)
adipocyte-secreted factors exacerbate lung epithelial cell inflammation. Our data and existing literature support
a novel hypothesis that IFNAR-dependent activation of adipocyte inflammatory capacity promotes
adipocyte IL-6 production and amplifies influenza infection-driven lung disease severity in obesity. We
propose to test this hypothesis by: (i) determining the impact of Influenza infection on adipocyte inflammatory
capacity and lung tissue damage in obesity (Aim 1); (ii) determining the contribution of adipocyte-centric IL-6
production on Influenza-associated tissue damage in obesity (Aim 2). Our studies will enhance the knowledge
of adipocyte-driven inflammatory vigor and the impact of such inflammation on human disease. Considering the
global trend towards a more obese population, defining the contribution of these cellular inflammatory processes
will provide a robust platform for discovery of novel therapeutic targets to reduce the clinical burden of influenza.

## Key facts

- **NIH application ID:** 10462898
- **Project number:** 1F31AI169757-01
- **Recipient organization:** CINCINNATI CHILDRENS HOSP MED CTR
- **Principal Investigator:** Pablo Alarcon
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $41,163
- **Award type:** 1
- **Project period:** 2022-09-01 → 2024-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10462898

## Citation

> US National Institutes of Health, RePORTER application 10462898, Adipose Tissue Inflammation in Influenza Infection Severity (1F31AI169757-01). Retrieved via AI Analytics 2026-05-27 from https://api.ai-analytics.org/grant/nih/10462898. Licensed CC0.

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