# Phenotype-Tailored Lifestyle intervention for Obesity: A Randomized Trial

> **NIH NIH R01** · MAYO CLINIC ROCHESTER · 2024 · $674,391

## Abstract

PROJECT SUMMARY
Obesity is a chronic, relapsing, and multifactorial disease, with a prevalence of 42%. Obesity treatment is
challenging in clinical practice because of the physiologic and behavioral adaptations that occur during the
weight-reduced state to preserve energy. Our overall goal is to develop an evidence-based, phenotype-guided
approach for obesity treatment that enhances weight loss and induces weight loss maintenance despite weight-
reduced state adaptations. Our research has identified obesity phenotypes based on energy homeostasis and
behavioral traits. Obesity phenotypes include abnormal satiation (i.e., requiring more calories at each meal to
achieve fullness), abnormal postprandial satiety (i.e., accelerated gastric emptying and increased postprandial
hunger), emotional eating (i.e., eating in response to positive or negative emotions), and abnormal resting energy
expenditure (i.e., low resting energy expenditure). In pilot clinical studies, these obesity phenotypes have
predicted weight loss response to anti-obesity medications and bariatric endoscopic devices. We recently
published data from a 12-week proof-of-concept, non-randomized clinical trial of 165 patients in which 84
participants received lifestyle interventions designed for each phenotypic trait they had and 81 received standard
lifestyle recommendations. The phenotype-tailored lifestyle intervention (PLI) resulted in greater weight loss
compared to the standard lifestyle intervention (SLI) approach for obesity. Patients in the PLI showed
improvement of their phenotype-defining trait(s). Improvement in these traits may explain the greater weight loss
as they potentially counteract physiologic and behavioral adaptations of the weight-reduced state. To validate
these data, we must study PLI in a longer-term and randomized clinical trial. Furthermore, the current methods
used to identify phenotypes in our preliminary studies are time-consuming, invasive, expensive, limited to a few
academic centers, and not accessible for most patients. In an academic-industry partnership, we have developed
a novel biomarker test that predicts obesity phenotypes but that needs to be validated in a large prospective
cohort. As such, we have formulated the following central hypothesis: “tailoring lifestyle recommendations to
obesity phenotypes will enhance long-term weight loss outcomes in adult patients with obesity”. To test our
central hypothesis, we propose a 12-month randomized, blinded, parallel clinical trial in adults with
obesity to test three aims: 1) To compare the outcomes of PLI vs. SLI program; 2) After a 12-month weight loss
program, to compare the long-term effect of PLI compared to SLI on physiological (i.e., satiation, postprandial
satiety, energy expenditure) and behavioral (i.e., emotional eating) adaptations; and 3) To explore whether a
phenotype biomarker predicts weight loss in response to PLI compared to SLI. Significance: Our study has the
potential to introduce a...

## Key facts

- **NIH application ID:** 10853766
- **Project number:** 1R01DK139028-01
- **Recipient organization:** MAYO CLINIC ROCHESTER
- **Principal Investigator:** Andres J Acosta
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $674,391
- **Award type:** 1
- **Project period:** 2024-07-15 → 2029-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10853766

## Citation

> US National Institutes of Health, RePORTER application 10853766, Phenotype-Tailored Lifestyle intervention for Obesity: A Randomized Trial (1R01DK139028-01). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10853766. Licensed CC0.

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