# Immunometabolic regulations of pulmonary TB pathogenesis by adiposetissue

> **NIH NIH R01** · HACKENSACK UNIVERSITY MEDICAL CENTER · 2021 · $760,645

## Abstract

About one-third of the world's population is infected with Mycobacterium tuberculosis (Mtb), and ≈10% of these
individuals will at some point develop active tuberculosis (TB). The risk of TB reactivation is greater in people
affected by type 2 diabetes mellitus (T2DM) and HIV, whereas, paradoxically, obesity protects against TB
disease. The underlying molecular mechanisms that explain how these co-morbidities impact TB disease
progression are mostly unknown. Although many studies have implicated incompetent immune systems to
pulmonary TB reactivation pathogenesis, our published data links pulmonary TB pathogenesis and bacterial
burden to adipose tissue (AT) pathophysiology. The objective of this proposal is to dissect the role of
adipocytes/AT in regulating immuno-metabolic mechanisms underlying pulmonary pathogenesis and examine
the significance of fat loss or adipogenesis in the pathogenesis of pulmonary TB infection. Our central
hypothesis is that an acute loss of adipocytes perturbs immuno-metabolic homeostasis in the lungs and
upsets immune-cell activation via adiponectin (an anti-inflammatory adipokine) signaling during Mtb infection.
This hypothesis is strongly supported by our published data which demonstrates that ablation of fat cells
induces pulmonary expression of adiponectin, an anti-inflammatory adipokine, and increases the levels of
foamy macrophages and elevates Mtb burden in the lungs. In addition we showed that dying adipocytes
release apoptotic bodies (ApoBDs) that express adiponectin accumulate in the lungs and may mediate
pulmonary adipogenesis in infected mice. The central hypothesis will be tested by pursuing three specific aims:
1) To study the impact of fat ablation and adipogenesis in AT on pulmonary pathology and Mtb burden during
acute and chronic Mtb infections; 2) To examine the regulatory effect of gain or loss of fat cells on the
activation status of immune cells in AT and lung during acute and chronic stages of infection; and 3) To
investigate adipocytes communication mechanism(s) in regulating pulmonary adiponectin expression, immune
cells activation, and pathology during Mtb infection. This proposal is technically innovative in our use of a
combination of diet-induced adipogenic and fat-mass amendable murine TB models to manipulate body fat
mass to investigate the role of adipocytes and adipokines in regulating pulmonary TB infection severity. A
significant strength of this application is the proposed study design which includes a unique animal model, diet
intervention, different Mtb strains, two disease models and various in vitro studies. The proposed research is
significant, because it will identify the molecular links between adipocyte physiology and TB and dissect the
role of adiponectin signaling in the pathogenesis and severity of pulmonary TB infection. The results will have
an important positive impact because the proposed studies will help facilitate the identification of therapeutic
targets for early ...

## Key facts

- **NIH application ID:** 10237418
- **Project number:** 5R01AI150765-03
- **Recipient organization:** HACKENSACK UNIVERSITY MEDICAL CENTER
- **Principal Investigator:** Jyothi Falguni Nagajyothi
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $760,645
- **Award type:** 5
- **Project period:** 2020-01-10 → 2024-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10237418

## Citation

> US National Institutes of Health, RePORTER application 10237418, Immunometabolic regulations of pulmonary TB pathogenesis by adiposetissue (5R01AI150765-03). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10237418. Licensed CC0.

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