# Leptin Reduction as a Potent Mitigative Strategy for the Treatment of PASC

> **NIH NIH R01** · UT SOUTHWESTERN MEDICAL CENTER · 2022 · $791,569

## Abstract

Summary/Abstract
While many individuals infected with SARS-CoV2 have mild symptoms and may even be asymptomatic, some
patients experience fulminant pathology that can cause severe sequelae or even death. For others, the effects
of the acute response to the infection linger for many months (“Long-COVID”). The infection has the potential to
exasperate pre-existing conditions, in particular those related to metabolic disease. Several lines of evidence
suggest the potential for intervention to limit prolonged COVID-19 severity: 1) Infections are most problematic in
individuals with high risk metabolic syndrome; 2) The severity of the infection is associated with parameters that
are related to insulin resistance, including inflammation, elevated glucose levels with severe insulin resistance,
and increased liver damage. Hyperleptinemia and diabetes are common among the obese population, and it
has long been known that leptin plays an important role in regulating the immune system as well as metabolism.
We have taken an intense interest in the connection of obesity/diabetes and enhanced disease
severity/outcome over the past two years. Here, we aim to directly test the hypothesis that reducing
plasma leptin levels or increasing MSH levels has a positive impact on the immune system and fibrosis.
We will address these questions at the cellular, tissue and systemic level. Specifically, we want to: 1: Determine
the role of -MSH towards leptin-POMC signaling in mediating immune responses in the context of Long-
COVID centrally. 2: Determine whether leptin neutralization has an impact on lung fibrosis in the
bleomycin fibrosis model. 3: Determine whether leptin neutralization has an impact on inflammation
peripherally. 4: Determine the impact of leptin neutralization and leptin-lowering thiazolidinediones on
Long-Covid. Combined, these studies will test the effect of leptin neutralization, -MSH and PPAR
activation on disease outcome in long COVID. Both Scherer and Elmquist have track records in metabolism
and have teamed up with Jyothi Nagajyothi, an established infectious disease specialist and are further
supported by Deep Dixit at Yale and Jerry Colca from Cirius Inc. As a team between the three core laboratories,
we believe we have unique expertise and tools in hand to assess the effectiveness of these interventions,
including the increased subclinical inflammation, persistent fibrosis and deteriorated insulin sensitivity that
persists during Long-COVID. Our preliminary data strongly support the premise of leptin involvement in
the disease progression with leptin neutralizing antibodies reducing the viral load in a rodent COVID-19
model by 85% and effectively reconstituting at least partially adiponectin levels in the lung. Lipoblasts in the lung
express adiponectin, but lose it as they convert to fibrosis generating myofibroblasts. Leptin reduction through
the use of neutralizing anti-leptin antibodies seems to preserve lipoblast function.
We believe...

## Key facts

- **NIH application ID:** 10554019
- **Project number:** 3R01DK127274-02S1
- **Recipient organization:** UT SOUTHWESTERN MEDICAL CENTER
- **Principal Investigator:** JOEL K. ELMQUIST
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $791,569
- **Award type:** 3
- **Project period:** 2021-07-01 → 2025-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10554019

## Citation

> US National Institutes of Health, RePORTER application 10554019, Leptin Reduction as a Potent Mitigative Strategy for the Treatment of PASC (3R01DK127274-02S1). Retrieved via AI Analytics 2026-05-29 from https://api.ai-analytics.org/grant/nih/10554019. Licensed CC0.

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