# The Role of Adipocyte Lipolysis in Thermoregulation

> **NIH NIH R01** · UNIVERSITY OF MARYLAND BALTIMORE · 2022 · $431,816

## Abstract

Project Summary
Adipose tissue critically regulates whole-body energy homeostasis. Mammals have two major adipose tissues:
white adipose tissue (WAT) and brown adipose tissue (BAT). WAT stores excess energy while BAT dissipates
energy as heat for non-shivering thermogenesis. Some adipocytes in WAT, like brown adipocytes, express
uncoupling protein-1 (UCP1), a protein that mediates heat generation by un-coupling mitochondrial respiration
from ATP synthesis. This population of adipocytes is recently named “beige” or “brite” adipocytes. The quantity
of beige adipocytes increases during cold adaptation or sympathetic activation, a process referred to as WAT
browning. Mobilization of stored cellular energy for use during starvation or increased energy demand (e.g.,
cold adaptation) requires hydrolysis of triglycerides stored in cytosolic lipid droplets (LDs) (i.e., intracellular
lipolysis). A gene critically implicated in intracellular lipolysis is CGI-58 (Comparative Gene Identification-58). In
mammals, CGI-58 is ubiquitously expressed with the highest expression in fat. It interacts with LD coat
proteins and activates ATGL (Adipose Triglyceride Lipase) to promote intracellular lipolysis. It was believed
that intracellular lipolysis in BAT is essential for thermogenesis, but this has not been examined in vivo. We
surprisingly found that mice lacking CGI-58 in BAT, i.e., BAT-specific CGI-58 knockout (BAT-KO) mice, are not
cold sensitive even in the fasted state. This proposal is to define the underlying adaptive mechanisms. Our
preliminary studies suggest a central hypothesis: BAT deficiency in intracellular lipolysis may reprogram BAT
to take up more circulating thermogenic substrates derived from WAT lipolysis and diet and by inducing WAT
thermogenesis through activation of the sympathetic nervous system. We will test this hypothesis by examining
BAT thermogenesis, BAT uptake of circulating substrates, and WAT thermogenesis under different
temperature, sympathetic, and nutritional states. We will also explore the origin of beige adipocytes in BAT-KO
mice. Additionally, we will examine whether WAT lipolysis is required for thermogenesis and WAT browning in
BAT-KO mice by using a pharmacological inhibitor of intracellular lipolysis and by simultaneous deletion of
CGI-58 in both BAT and WAT (FAT-KO mice). In some experiments, we will compare adipose CGI-58 and
ATGL KO mice to gain insights into other lipolytic roles of CGI-58. Furthermore, we will define how BAT
lipolysis regulates energy balance, glucose disposal, insulin sensitivity, and tissue lipid metabolism. Finally, we
will search for novel insights into how lipolysis deficiency augments adipose sympathetic drive. We will
generally measure blood levels of lipids/adipokines/hormones, and tissue levels of lipids/gene expression to
establish how CGI-58 deficiency in different adipocytes regulates lipid/energy metabolism at biochemical and
molecular levels. Thermogenesis dissipates energy. Perturbat...

## Key facts

- **NIH application ID:** 10225316
- **Project number:** 5R01DK116496-05
- **Recipient organization:** UNIVERSITY OF MARYLAND BALTIMORE
- **Principal Investigator:** Liqing Yu
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $431,816
- **Award type:** 5
- **Project period:** 2018-06-15 → 2024-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10225316

## Citation

> US National Institutes of Health, RePORTER application 10225316, The Role of Adipocyte Lipolysis in Thermoregulation (5R01DK116496-05). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10225316. Licensed CC0.

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