# Lipid storage and utilization in physiology and obesity

> **NIH NIH R01** · UNIVERSITY OF CALIFORNIA LOS ANGELES · 2023 · $553,800

## Abstract

ABSTRACT
 A major goal of our laboratory is to delineate regulatory mechanisms that control adipocyte development
and systemic physiology in obesity and diabetes. This proposal will address a new regulatory pathway
involved in adipose tissue adipose depot-specific energy expenditure. Understanding how metabolic tissues
store and utilize lipids is of central relevance to normal physiology, obesity and diabetes. Excess neutral lipids
are stored in lipid droplets (LDs)–dynamic organelles that expand and shrink depending on the metabolic
needs of the cell. The molecular mechanisms that link lipid LD dynamics and function to tissue metabolism are
incompletely understood. Defining the molecular pathways that govern fuel utilization in tissues is important for
understanding systemic homeostasis and the underlying causes of pathological lipid accumulation in the
setting of metabolic disease. We have identified Clstn3, an adipose tissue- and liver-selective product of the
Clstn3 gene, as a key determinant of multilocular LD morphology and function. Clstn3 is an integral ER
membrane protein that localizes to ER-LD contact sites via conserved hairpin-like domains. Loss of Clstn3 in
mouse brown adipose tissue (BAT) increases LD size, reduces triglyceride utilization, and leads to cold-
induced hypothermia. Conversely, ectopic expression of Clstn3 in adipocytes is sufficient to reduce LD size
and enforce a multilocular LD phenotype. Collectively, these initial discoveries have revealed a previously
unrecognized molecular mechanism that maximizes LD surface area and facilitates lipid utilization in
thermogenic adipocytes and potentially other cells. The overall goal of this proposal is to further define the
mechanisms of Clstn3 action and its contributions to metabolic physiology. Specific Aim 1 will elucidate
mechanisms by which Clstn3 regulates LD structure and function. Specific Aim 2 will investigate the ability of
Clstn3 to modify white adipocyte function. Specific Aim 3 will define the role of Clstn3 in lipid metabolism in
other tissues. These studies are expected to provide fundamental insight into pathways regulating LD function
and may suggest opportunities for modulating lipid utilization in the setting of metabolic disease.

## Key facts

- **NIH application ID:** 10663760
- **Project number:** 1R01DK136150-01
- **Recipient organization:** UNIVERSITY OF CALIFORNIA LOS ANGELES
- **Principal Investigator:** PETER J TONTONOZ
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2023
- **Award amount:** $553,800
- **Award type:** 1
- **Project period:** 2023-05-01 → 2027-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10663760

## Citation

> US National Institutes of Health, RePORTER application 10663760, Lipid storage and utilization in physiology and obesity (1R01DK136150-01). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10663760. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*