# Investigating the influence of mTOR signaling on lipid metabolism in adipose tissue.

> **NIH NIH F31** · UNIVERSITY OF PENNSYLVANIA · 2020 · $35,472

## Abstract

Project Summary
Rapamycin, which is FDA approved as an anti-rejection agent, has been extensively shown to extend
lifespan and delay the onset of age related diseases across several model organisms. However,
patients treated with rapamycin develop several metabolic abnormalities, including glucose intolerance,
insulin insensitivity and hyperlipidemia, preventing the therapeutic use as an anti-ageing agent.
Rapamycin is an allosteric inhibitor of mTOR (mechanistic target of rapamycin), a serine/threonine
protein kinase that functions as a master regulator of cellular growth and metabolism. mTOR plays an
important role in metabolic tissues, such as the liver, skeletal muscle and adipose tissue. Tissue
specific disruption of mTORC1 or mTORC2 has revealed that each complex has different effects on
whole body glucose and lipid homeostasis in different organs.
 It is known that mTOR signaling regulates lipid homeostasis and that rapamycin blocks
expression of genes involved in lipogenesis and impairs the nuclear accumulation of SREBPs.
Preliminary data suggest that mTOR loss in the liver is not responsible for the elevated serum
cholesterol and triglyceride levels seen with rapamycin treatment. Many groups have shown that mTOR
signaling in adipose tissue regulates lipid synthesis through various effectors, but the mechanisms are
not fully understood. To understand how mTOR signaling in adipose tissue and rapamycin affects
metabolism, specifically on lipid homeostasis, I will use genetic mTOR adipose specific knockout
mouse models and wildtype mice treated with rapamycin. These mice will be used for turnover studies
with HDL and VLDL labeled with tracers, and phosphoproteomics. Together, this proposal will provide
an improved understanding on mTOR and rapamycin which will aid in the therapeutic uses of
rapamycin by avoiding such side effects as hyperlipidemia.

## Key facts

- **NIH application ID:** 9830533
- **Project number:** 5F31AG057171-03
- **Recipient organization:** UNIVERSITY OF PENNSYLVANIA
- **Principal Investigator:** LAUREN Michele PAOLELLA
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $35,472
- **Award type:** 5
- **Project period:** 2018-01-01 → 2020-08-07

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9830533

## Citation

> US National Institutes of Health, RePORTER application 9830533, Investigating the influence of mTOR signaling on lipid metabolism in adipose tissue. (5F31AG057171-03). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/9830533. Licensed CC0.

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