# Methionine Aminopeptidase 2 Regulates Lipid Metabolism in Peripheral Tissues

> **NIH NIH F32** · UT SOUTHWESTERN MEDICAL CENTER · 2021 · $35,229

## Abstract

Project Summary
Obesity is the result of a chronic, relapsing progressive disease process that has become a global pandemic.
Reductions in weight as small as 5-10% drastically help reduce the comorbidities of obesity, however weight
loss is extremely difficult to maintain. Anti-obesity drugs are promising interventions to help overcome the
challenge of maintaining weight loss, yet most have been withdrawn due to serious side effects. For this
reason, further research is needed on strategies for producing sustained weight loss. One drug class currently
being tested in clinical trails, methionine aminopeptidase 2 (MetAP2) inhibitors, rapidly reduce body weight,
increase glycemic control, and reduce serum lipids. Remarkably, clinical trials with MetAP2i are ongoing
despite the fact we know little about how MetAP2 mediates anti-obesogenic effects. In vitro studies have
shown that MetAP2 is a multifunctional protein that removes the N-terminal methionine residue from newly
translated proteins, but can also directly impact major cell signaling pathways. In the past, it has been
challenging to study the effects of MetAP2 expression in vivo, because the developmental models of MetAP2
elimination are embryonically lethal. To overcome this problem, we have generated mouse models that
overexpress or knockdown MetAP2 in an inducible, tissue-specific manner. These mouse models will allow us
to examine the systemic effects and molecular mechanisms of MetAP2 expression in two major peripheral
organs that regulate glucose and lipid metabolism during obesity: liver and adipose tissue. Only after
understanding the mechanisms that underlie the cellular effects of MetAP2, will we begin to understand how
MetAP2 or MetAP2 inhibitors take part in the complex regulation of whole-body energy balance. Specifically, in
Aim 1 we will determine whether MetAP2 expression in adipocytes and hepatocytes regulate body weight,
energy expenditure, glucose tolerance, and serum lipid levels. The goal of Aim 2 is to examine whether the
three known MetAP2 mechanisms discovered in vitro are found to be relevant to liver and adipose tissue lipid
metabolism in vivo.

## Key facts

- **NIH application ID:** 10388782
- **Project number:** 3F32DK122623-02S1
- **Recipient organization:** UT SOUTHWESTERN MEDICAL CENTER
- **Principal Investigator:** Christy M Gliniak
- **Activity code:** F32 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $35,229
- **Award type:** 3
- **Project period:** 2019-12-01 → 2022-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10388782

## Citation

> US National Institutes of Health, RePORTER application 10388782, Methionine Aminopeptidase 2 Regulates Lipid Metabolism in Peripheral Tissues (3F32DK122623-02S1). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10388782. Licensed CC0.

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