# Metabolic Impacts of Type II Interferon Signals in Obesity

> **NIH NIH R01** · BAYLOR COLLEGE OF MEDICINE · 2022 · $552,838

## Abstract

ABSTRACT
Obesity coincides with pro-inflammatory phenotypes in adipose tissues and the insulin resistance that precedes
type 2 diabetes. Despite a wealth of evidence, causal relationships between obesity-induced inflammation and
insulin resistance remain unknown. In the last grant cycle, we explored how inflammation uncouples obesity
from insulin resistance. We showed blocking interferon gamma (IFN) activation of the transcription factor STAT1
limits pro-inflammatory programs that would otherwise restrict white adipose tissue (WAT) expansion and
decrease insulin sensitivity. We also demonstrated complete elimination of IFN activity mediates many adverse
effects of high fat diet, including weight gain, diminished mitochondrial function, and insulin resistance. Multiple
studies, including our own, observed higher STAT1 expression in WAT of diabetic mice and humans, suggesting
that IFN activity may still represent a pathogenic consequence of chronic obesity. The goal of the current cycle
is to fill vital remaining gaps in our mechanistic understanding of the fundamental ways IFN transmits signals to
transcriptional regulation of metabolism and insulin sensitivity in fat cells. To achieve our goal, we will
demonstrate that the IFN receptor in WAT initiates the metabolic decrement of overnutrition (Aim 1) and
establish the downstream transcriptional outcomes of IFN that repress cellular energy balance in the fat cell
(Aim 2). Lastly, we will determine whether obesity-associated inflammation restricts a novel pathway that
supports lipogenic responses necessary to sustain WAT expansion (Aim 3). Ultimately, such knowledge will
teach us how to leverage the immune system to treat obesity and its co-morbidities.

## Key facts

- **NIH application ID:** 10520940
- **Project number:** 2R01DK114356-06A1
- **Recipient organization:** BAYLOR COLLEGE OF MEDICINE
- **Principal Investigator:** Sean Hartig
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $552,838
- **Award type:** 2
- **Project period:** 2017-08-18 → 2026-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10520940

## Citation

> US National Institutes of Health, RePORTER application 10520940, Metabolic Impacts of Type II Interferon Signals in Obesity (2R01DK114356-06A1). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10520940. Licensed CC0.

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