# Lnc'ing White Fat to Brown Fat Thermogenesis

> **NIH NIH DP1** · DANA-FARBER CANCER INST · 2020 · $885,000

## Abstract

ABSTRACT
Approximately 160 million American men, women and children are overweight or obese. Almost 75% of men,
60% of women and 30% of boys and girls under the age of 20 are obese or overweight. Obesity is associated
with numerous co-morbidities including diabetes, cardiovascular disease, and cancers. There are two types of
fat. Brown fat is common in newborns and small mammals. It is useful for generating heat, especially in small
bodies that tend to lose heat. White fat increases as people age and is useful for storing energy and insulating
against heat loss. Increased white fat is associated with increased obesity-related disease whereas increased
brown fat is associated with reduced obesity-related disease.
Several recent studies of adipose tissue have identified transcriptional signatures associated with brown fat
adipogenesis and specifically thermogenic programs. Some of these studies have also identified long non-
coding RNAs (lncRNAs) associated with white fat and brown fat identity and function. However, the
mechanism(s) of how these lncRNAs affect transcriptional programs and determine brown fat identity and
function are poorly understood.
We propose to use our recently developed lncRNA-based yeast three hybrid (Y3H) assay to systematically
define lncRNA-protein interactions for 318 conserved lncRNAs implicated in brown fat adipogenesis. Our Y3H
system is capable of detecting lncRNA-protein interactions that are otherwise difficult to detect due to issues of
low-abundance and low-affinity interactions. Overlaying lncRNA-protein interactions onto existing protein-
protein interaction networks will define lncRNA-regulated pathways of normal brown fat adipogenesis and will
also identify lncRNA-regulated pathways that might be manipulated to increase thermogenesis. Because we
will screen overlapping lncRNA fragments of these 318 individual lncRNAs, these studies will enable
systematic lncRNA structure-function analyses. The information obtained through this structure-function
analysis will be critical for establishing sequence and/or structural parameters which may enable prediction of
lncRNA-protein binding activity, thereby advancing our understanding of the biology of lncRNAs, even those
not included in this initial screen.
For a set of lncRNA-protein interactions, we will validate roles in mouse models of brown fat adipogenesis by
increasing (by ectopic expression) or decreasing (by knockdown) lncRNAs and their associated proteins in
brown fat progenitor cells. We will assess the effects of these interactions by testing obesity, brown fat lineage
commitment (by FACS analysis) and thermogenesis (by transcriptional profiling). Thus, these studies will (1)
identify lncRNA-protein interactions directing adipogenesis and thermogenesis; (2) develop a platform for
systemically studying lncRNAs; and (3) provide pre-clinical evidence support clinical trials targeting lncRNA-
directed pathways for obesity-related diseases.

## Key facts

- **NIH application ID:** 10064214
- **Project number:** 1DP1DK126161-01
- **Recipient organization:** DANA-FARBER CANCER INST
- **Principal Investigator:** CARL D NOVINA
- **Activity code:** DP1 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $885,000
- **Award type:** 1
- **Project period:** 2020-09-11 → 2022-09-10

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10064214

## Citation

> US National Institutes of Health, RePORTER application 10064214, Lnc'ing White Fat to Brown Fat Thermogenesis (1DP1DK126161-01). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10064214. Licensed CC0.

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