# Accumbal adaptations that contribute to weight regain after weight loss

> **NIH NIH R01** · WASHINGTON UNIVERSITY · 2024 · $494,953

## Abstract

Project Summary/Abstract
Losing weight can be life saving for people with obesity. However, among patients that do lose significant
weight, most have trouble keeping the weight off. People with obesity that lose weight experience
physiological, neural, and behavioral changes that drive weight regain. These changes resemble adaptive
mechanisms that defend body weight during periods of food scarcity, but for people trying to achieve a healthy
body weight and stay there, these mechanisms are decidedly maladaptive. Intervening to counteract them has
the potential to revolutionize the clinical approach to weight loss for people with obesity. The objective of this
proposal is to understand how the function of a brain area known as the nucleus accumbens is altered across
the weight “gain-loss-regain” cycle in mice. Our central hypothesis is that obesity is associated with
adaptations in the brain’s reward circuitry that enhance the pursuit of palatable foods, promoting weight regain
after obese animals lose weight, and thereby perpetuating this cycle. In Aim 1, we will use ex vivo
electrophysiological approaches to monitor changes in intrinsic and synaptic properties of accumbal neurons
as obese mice lose weight, critically determining adaptations that persist after weight loss. In Aim 2, we will
employ in vivo calcium imaging to measure the activity of specific populations of accumbal neurons as mice
gain, lose, and regain weight. Finally, in Aim 3 we will use viral genetic strategies to selectively silence specific
populations of accumbal neurons to determine whether this: 1) facilitates weight loss in obese mice that remain
on a high-fat diet; and/or 2) inhibits weight re-gain in formerly obese mice who have lost weight. Our long-term
goal is to understand how obesity alters reward circuitry and discover methods for reversing these changes.
This research will provide a critical foundation to advance efforts to improve weight loss outcomes in people
with obesity.

## Key facts

- **NIH application ID:** 10781678
- **Project number:** 1R01DK138131-01
- **Recipient organization:** WASHINGTON UNIVERSITY
- **Principal Investigator:** Alexxai V Kravitz
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $494,953
- **Award type:** 1
- **Project period:** 2024-04-01 → 2028-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10781678

## Citation

> US National Institutes of Health, RePORTER application 10781678, Accumbal adaptations that contribute to weight regain after weight loss (1R01DK138131-01). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10781678. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*