# Autoimmune Basis of Acquired Lipodystrophies

> **NIH NIH R01** · UT SOUTHWESTERN MEDICAL CENTER · 2024 · $703,888

## Abstract

Obesity remains a major health problem in US and causes metabolic complications such as
diabetes, dyslipidemia and insulin resistance. Similar complications also occur in patients with
autoimmune lipodystrophies characterized by almost complete (acquired generalized
lipodystrophy or AGL) or partial (acquired partial lipodystrophy, APL) loss of body fat. Recently,
circulating autoantibody against perilipin-1 (PLIN1) has been implicated in the pathogenesis of
AGL. However, nearly two-thirds of AGL patients do not have PLIN1 autoantibodies suggesting
other adipocyte antigens may be involved in the autoimmune response. Furthermore, the
pathogenesis of APL remains unknown. Thus, the first two aims of this proposal are to identify
additional autoantibodies against adipocyte expressed proteins that cause AGL or APL and to
determine their function in adipocyte biology. We will use two state-of-the-art complementary
techniques, a. Phage ImmunoPrecipitation Sequencing (PhIP-Seq) Assay and b. Human
Proteome Microarray (HuProtTM version 4 Chip) to identify the serum autoantibodies in AGL and
APL patients. Our recent data from a mouse model of human autoimmune polyglandular
syndrome type 1)(Aire-/- mice) reveal circulating PLIN1 autoantibodies and loss of both
subcutaneous and visceral fat due to inflammatory lesions in adipose tissue. Therefore, the third
aim of our proposal is to determine underlying autoimmune mechanisms involved in loss of
tolerance to perilipin-1 in Aire-/- mice. Lastly, we will determine pathogenicity of novel
autoantibodies discovered in patients with AGL and APL against adipocyte expressed proteins
by infusing them into mice and evaluating loss of body fat, development of insulin resistance and
metabolic derangements. These studies will unravel autoimmune mechanisms involved in
causation of lipodystrophy, and insulin resistance and its associated morbidities. This new
knowledge may provide targets for developing novel drugs for treating diabetes, dyslipidemias
and hepatic steatosis.

## Key facts

- **NIH application ID:** 10981898
- **Project number:** 1R01DK137904-01A1
- **Recipient organization:** UT SOUTHWESTERN MEDICAL CENTER
- **Principal Investigator:** Mark S Anderson
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $703,888
- **Award type:** 1
- **Project period:** 2024-09-01 → 2028-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10981898

## Citation

> US National Institutes of Health, RePORTER application 10981898, Autoimmune Basis of Acquired Lipodystrophies (1R01DK137904-01A1). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10981898. Licensed CC0.

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