# Long Non-coding RNA as Mediators of Metabolic Disease

> **NIH NIH R01** · UNIV OF MASSACHUSETTS MED SCH WORCESTER · 2020 · $423,449

## Abstract

Obesity, diabetes, and accompanying lipid and blood pressure dysregulation—collectively termed
“cardiometabolic disease” (CMD)—is a major contributor to cardiovascular disease. Despite long-standing data
implicating small non-coding RNAs in CMD, less is known in regards to long non-coding RNAs (lncRNAs).
Animal studies have recently suggested a role for lncRNAs in lipid homeostasis, fat thermogenesis and
myocardial remodeling, each critical to CMD. While animal studies may heighten a suspicion for lncRNAs in
CMD, studies in human tissue are imperative to establish their role. Studies focused on lncRNA expression in
tissues central to CMD in humans are crucial to understand novel aspects of the molecular physiology of CMD
and its downstream impact on cardiovascular health. Brown adipose tissue (BAT), central in energy
expenditure regulation and metabolism, is inversely correlated with body-mass index (BMI). Preliminary data
from our group using human adipocytes from BAT and white adipose tissue (WAT) has identified specific
lncRNAs that are differentially expressed and altered in proportion with increasing BMI and diabetes. Currently,
in silico determination of lncRNA-mRNA regulation remains problematic (due to lack of curated resources), and
large-scale validation in accessible tissue (e.g., plasma) from populations at-risk for CMD and downstream
cardiovascular risk is lacking. Therefore, understanding the role of lncRNAs in humans must (1) be performed
in human tissues relevant to CMD; (2) identify coordinate changes between lncRNA and mRNA expression (as
possible targets of lncRNA regulation); (3) include association studies between lncRNAs and CMD phenotypes
to enable future larger mechanistic studies in CMD.
 Here, we hypothesize that lncRNAs differentially expressed in BAT vs. WAT or relevant in adipogenesis
will be (1) associated with expression of genes central to CMD pathogenesis and (2) dynamically expressed in
plasma as a function of cardiometabolic perturbations known to impact CMD and cardiovascular disease (e.g.,
bariatric surgery, insulin resistance). To address this central hypothesis, we bring together our preliminary
human adipose tissue RNA-seq data with several very unique resources: (1) ongoing WAT, BAT, and plasma
collection from prospective resources at the NIH Clinical Center and our institution; (2) an NIH-funded study of
individuals pre-/post-bariatric surgery in which we have performed non-coding RNA quantification
(U54HL112311) and have preliminary data establishing large changes in lncRNAs with weight loss; (3)
population-wide data (n=3100) including CMD, mRNA measurements, and available RNA for lncRNA
analyses. This application is based on preliminary data providing candidate lncRNAs that are differentially
expressed in metabolically active fat. It is bolstered by active collaborations and samples previously collected
from NIH/NHLBI sponsored studies, as well as innovative bioinformatics methods to identify possible l...

## Key facts

- **NIH application ID:** 9856461
- **Project number:** 5R01HL145721-02
- **Recipient organization:** UNIV OF MASSACHUSETTS MED SCH WORCESTER
- **Principal Investigator:** JANE E Freedman
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $423,449
- **Award type:** 5
- **Project period:** 2019-02-01 → 2023-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9856461

## Citation

> US National Institutes of Health, RePORTER application 9856461, Long Non-coding RNA as Mediators of Metabolic Disease (5R01HL145721-02). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9856461. Licensed CC0.

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