# Immune pathways in adipose thermogenesis

> **NIH NIH R01** · UNIVERSITY OF CALIFORNIA LOS ANGELES · 2022 · $455,553

## Abstract

Abstract
Adipose tissue plays a central role in metabolic and energy homeostasis, and dysregulation of adipocyte
function is fundamental to the pathogenesis of the metabolic syndrome. Our group has a track record of
identifying and characterizing important proteins involved in adipocyte biology, including PPARγ, TLE3, and
PSPC1. Recently, we uncovered a novel physiological regulator of adipose thermogenic activity: the cytokine
IL10. This proposal builds upon this discovery to address important questions regarding the regulation of
systemic metabolism, adipose thermogenesis, and the crosstalk between immune cells and adipocytes within
adipose tissue depots. Regulatory pathways that stimulate adipose tissue thermogenesis have been
extensively characterized, but the limiters of energy expenditure have remained poorly defined. We have
discovered that IL10 signaling through STAT3 in adipocytes regulates thermogenic gene expression and
energy expenditure. The IL10 receptor alpha (IL10Rα) is highly enriched in mature adipocytes and is induced
in response to differentiation, obesity, and aging. Preliminary data indicate that IL-10 signaling inhibits beta-
adrenergic signaling in beige adipocytes, and reduces the occupancy of ATF and C/EBPβ on thermogenic
gene promoters. Moreover, inhibiting the expression of the IL10 receptor alpha (IL10Rα) in adipose tissue with
antisense oligonucleotides (ASOs) is protective against diet-induced obesity, suggesting that the adipose IL10
axis might be targeted therapeutically. Here we propose to further define the specific cell types and tissues
that produce and receive IL-10 signals affecting metabolism, to elucidate the mechanisms by which IL10
signaling regulates adipocyte gene expression, and to understand the roles of adipose tissue immune cell
populations in the regulation of thermogenesis by IL10. Specific Aim 1 is to characterize the adipocyte-intrinsic
role of IL-10 signaling in lipid storage and thermogenesis in adipose tissue. Specific Aim 2 is to define the
mechanisms underlying transcriptional modulation of thermogenesis by IL-10. Specific Aim 3 is to delineate
the role of adipose tissue-resident immune cells in the regulation of thermogenesis by IL10.

## Key facts

- **NIH application ID:** 10460987
- **Project number:** 5R01DK120851-04
- **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:** $455,553
- **Award type:** 5
- **Project period:** 2019-09-16 → 2023-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10460987

## Citation

> US National Institutes of Health, RePORTER application 10460987, Immune pathways in adipose thermogenesis (5R01DK120851-04). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10460987. Licensed CC0.

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