# A mechanism of lipid accumulation in brown adipose tissue

> **NIH NIH F31** · UNIVERSITY OF PENNSYLVANIA · 2024 · $40,480

## Abstract

PROJECT SUMMARY
Human variants in the cytoskeleton-associated protein ankyrin-B (AnkB) have been identified as risk factors for
metabolic disorders, including type 2 diabetes and obesity. Mice harboring these variants exhibit AnkB deficiency
in metabolic tissues including white (WAT) and brown adipose tissue (BAT), and develop age and diet-dependent
adiposity, insulin resistance, and glucose mishandling. Simultaneous AnkB deficiency in WAT and BAT also lead
to lipid accumulation in BAT (BAT “whitening”) and to decreases in energy expenditure and oxygen consumption.
These findings suggest that AnkB may function as an important regulator of lipid metabolism and systemic
metabolic regulation through its unexplored roles in BAT. The overarching goal of this study is to elucidate the
cell-autonomous roles of AnkB in BAT. We hypothesize that AnkB regulates lipogenesis in BAT and is required
for maintaining the energetic and glucose-handling capacity of BAT in response to metabolic stressors. To
answer these questions, we proposed to determine the molecular mechanism of association with AnkB
modulation of glucose handling and lipid metabolism in brown adipocytes (aim 1). Additionally, we will define
how AnkB deficiency in BAT regulates energy balance and systemic metabolic homeostasis in response to the
metabolic stressors, such as aging and high-fat diet (aim 2). Completion of the proposed studies will provide
functional insights into AnkB’s contribution to BAT physiology and metabolic homeostasis. The proposed work
will also shed light into the pathophysiological mechanism through which human AnkB variants contribute to
metabolic diseases.

## Key facts

- **NIH application ID:** 10813008
- **Project number:** 5F31DK134160-02
- **Recipient organization:** UNIVERSITY OF PENNSYLVANIA
- **Principal Investigator:** Ashley Aguillard
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $40,480
- **Award type:** 5
- **Project period:** 2023-04-01 → 2026-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10813008

## Citation

> US National Institutes of Health, RePORTER application 10813008, A mechanism of lipid accumulation in brown adipose tissue (5F31DK134160-02). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10813008. Licensed CC0.

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