# Membrane homeostasis in adipose physiology and obesity

> **NIH NIH R01** · UNIVERSITY OF CALIFORNIA LOS ANGELES · 2022 · $470,590

## Abstract

ABSTRACT
 A major long-term goal of our laboratory is to delineate regulatory mechanisms that control adipocyte
development and systemic physiology. This proposal will address a new regulatory pathway involved in
adipocyte nutrient sensing, adipose tissue physiology, and adipose depot-specific energy expenditure. The
proposed studies are focused on understanding how dynamic regulation adipocyte membrane composition
contributes to the control of whole-body metabolic homeostasis in living animals. Preliminary data implicates
the phospholipid remodeling enzyme Lpcat3 as novel mechanistic link between dietary fatty acid intake,
adipose tissue homeostasis, and susceptibility to obesity. This proposal builds upon our preliminary
discoveries to address important questions regarding the relationship of membrane lipid composition to
adipose tissue function and systemic physiology and energy balance. We have previously shown that the
enzyme Lpcat3 is uniquely required for the incorporation of the 6 polyunsaturated fatty acids into
phospholipids. Our preliminary data reveal that adipose Lpcat3 expression is induced in the setting of cold
exposure or diet-induced obesity. Moreover, initial characterization of mice lacking Lpcat3 selectively in
adipose tissues has revealed two distinct phenotypes: one traced to white adipose tissue (WAT) and one
traced to brown adipose tissue (BAT). Adipose Lpcat3 KO mice fed a high-fat diet develop a lipodystrophic
phenotype are unable to appropriately expand their WAT, leading to ectopic hepatic lipid accumulation and the
compensatory upregulation of fatty acid oxidation in WAT. At the same time, BAT Lpcat3 KO mice show an
abnormal response to cold challenge, characterized by marked ER stress. A striking commonality between
these WAT and BAT KO models is the compensatory production of FGF21 in an apparent effort to maintain
energy homeostasis. We hypothesize that the fine tuning of adipose tissue membrane composition by Lpcat3
is a critical adaptive response to cold and dietary challenge that permits optimal lipid storage and catabolic
function in a range of environments. We will address these hypotheses with the following specific aims.
Specific Aim 1 is to elucidate the role of membrane phospholipid remodeling in nutrient sensing and healthy
adipose tissue expansion. Specific Aim 2 is to determine the role of phospholipid remodeling in BAT function
and response to thermal stress.

## Key facts

- **NIH application ID:** 10455597
- **Project number:** 5R01DK129276-02
- **Recipient organization:** UNIVERSITY OF CALIFORNIA LOS ANGELES
- **Principal Investigator:** PETER J TONTONOZ
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $470,590
- **Award type:** 5
- **Project period:** 2021-07-22 → 2025-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10455597

## Citation

> US National Institutes of Health, RePORTER application 10455597, Membrane homeostasis in adipose physiology and obesity (5R01DK129276-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10455597. Licensed CC0.

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