# Regulation of Systemic Metabolism by Immune Cell Nutrient Sensing Pathways

> **NIH NIH F31** · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · 2020 · $50,520

## Abstract

PROJECT SUMMARY/ABSTRACT
It is well established that obesity leads to a drastic change in the immune cell landscape. This change
results in insulin resistance. However, the reverse is understudied: does changing the immune cell
landscape lead to obesity? CD11c+ cells are key cells in the immune system and have been shown to
play a role in regulating systemic metabolism. The tuberous sclerosis 1 - mechanistic target of
rapamycin complex 1 (Tsc1-mTORC1) pathway is the cell's major nutrient-level-sensing pathway. It
determines whether energy-intensive processes, such as protein translation, should take place
depending on availability of nutrients and growth factors. Given this knowledge, we asked: how does
perturbing nutrient sensing in immune cells affect systemic metabolism? To test this, an animal model
was developed in which Tsc1 was specifically knocked out in CD11c+ cells: Tsc1flox/flox (“control; CTRL”)
and CD11cCre x Tsc1flox/flox (“knockout; KO”) mice on a C57BL/6J background. We observed that KO
mice were protected from high fat diet (HFD)-induced weight gain and insulin resistance. The proposed
work aims to test the hypothesis that activation of nutrient sensing pathways in CD11c+ immune cells is
sufficient to modulate systemic metabolism. Aim 1 will determine how nutrient sensing by immune cells
regulates body weight, adiposity and insulin action. To test this, I will characterize the metabolic
phenotype of KO and CTRL mice under different dietary stress and housing temperatures. Aim 2 will
investigate the molecular mechanisms by which alterations in nutrient sensing in immune cells
regulates glucose and energy homeostasis. My preliminary data suggests that FGF21 is a potential
secreted factor that can regulate systemic metabolism in these animals. Completion of this project will
further our understanding of the role immune cells play in regulating systemic metabolism and have
immediate translational implications for the treatment of obesity and insulin resistance.

## Key facts

- **NIH application ID:** 9836844
- **Project number:** 5F31DK112669-03
- **Recipient organization:** UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
- **Principal Investigator:** DANAI NYASHA CHAGWEDERA
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $50,520
- **Award type:** 5
- **Project period:** 2017-12-01 → 2020-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9836844

## Citation

> US National Institutes of Health, RePORTER application 9836844, Regulation of Systemic Metabolism by Immune Cell Nutrient Sensing Pathways (5F31DK112669-03). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9836844. Licensed CC0.

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