# The Effect of Behavioral Weight Loss on Circulating Extracellular RNA

> **NIH NIH R21** · UNIV OF MASSACHUSETTS MED SCH WORCESTER · 2020 · $125,625

## Abstract

PROJECT SUMMARY
 The notion that not all obese individuals are at the same metabolic risk and that different types and/or
degrees of weight loss alter this risk is debated. Genetic variation and metabolite profiles have been proposed
to resolve metabolic risk in the obese, though the risk attributed to genetics and metabolites remains small.
Novel markers that identify sub-phenotypes of metabolic risk in the obese are therefore necessary to better
understand mechanism, determine the roll of weight loss, and uncover pathways for therapeutic targeting.
Plasma extracellular RNAs (ex-RNAs) are circulating RNAs involved in trans-organ communication in obesity,
epigenetically regulating a complex architecture of gene expression in adipocytes, hepatocytes, and skeletal
muscle to reinforce metabolic syndrome. We recently used RNA sequencing and high-throughput RT-qPCR to
identify plasma ex-RNAs associated with insulin resistance, visceral and hepatic fat, and obesity in several
thousand individuals and validated the association with insulin resistance in an obese pediatric population and
demonstrated alteration after extreme weight loss and diabetes resolution post bariatric surgery.
 In the U.S., the 2016 prevalence of obesity was 39.8% and affected about 93.3 million adults. Despite
the benefits of surgical weight loss, its extensive risks preclude routine utilization and the vast majority of
obese and overweight individuals employ behavioral and dietary approaches. Unknown is the impact of these
significantly more common patterns of weight loss and potential regain on inflammatory/epigenetic markers
including ex-RNAs that are associated with and contribute to metabolic risk. The Weight Loss Maintenance
Randomized Controlled Trial was a two-phase study in which 1032 overweight or obese adults who had lost at
least 4 kg during a 6-month weight loss program (phase 1) were randomized to a weight-loss maintenance
intervention (phase 2). To determine the impact of behavioral weight loss and regain on circulating gene
expression, we propose to; (1) determine if patterns of circulating ex-RNA expression from behavioral weight
loss are similar to bariatric surgical weight loss; (2) determine if specific patterns of ex-RNAs predict individuals
with sustained weight loss vs. regain; and (3) obtain preliminary proteomic data to confirm molecular targets.
The central hypothesis of this proposal is that plasma ex-RNAs known to be associated with metabolic
syndrome are altered after behavioral weight loss and detrimental patterns are influenced by changes in
weight.
 This proposal will leverage strong existing data and utilize technologies and bioinformatics established
in our laboratory to apply a transcriptomic approach to understand the molecular underpinnings of obesity and
uncover potential novel mediators associated with non-surgical weight loss. Data from this project would be
utilized to expand the study with validation in a broader population, contributing ...

## Key facts

- **NIH application ID:** 10041786
- **Project number:** 1R21HL147831-01A1
- **Recipient organization:** UNIV OF MASSACHUSETTS MED SCH WORCESTER
- **Principal Investigator:** JANE E Freedman
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $125,625
- **Award type:** 1
- **Project period:** 2020-08-01 → 2022-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10041786

## Citation

> US National Institutes of Health, RePORTER application 10041786, The Effect of Behavioral Weight Loss on Circulating Extracellular RNA (1R21HL147831-01A1). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10041786. Licensed CC0.

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