Brain circuit linking leptin signals to overeating of tasty, high‑fat foods

A leptin-responsive lateral hypothalamus to ventrolateral periaqueductal gray circuit for palatable food overconsumption

NIH-funded research Virginia Polytechnic Inst and St Univ · NIH-11325731

This project looks at how a leptin‑responsive brain pathway may drive renewed overeating of high‑fat, highly palatable foods in people who tend to regain weight after dieting.

Quick facts

Grant typeR01 grant
Study typeNIH-funded research
Funding institutionVirginia Polytechnic Inst and St Univ NIH-funded
Lab location1 site (Blacksburg, United States)
Project IDNIH-11325731 on NIH RePORTER

What this research studies

Researchers will map and manipulate a specific brain circuit between the lateral hypothalamus and the ventrolateral periaqueductal gray that responds to the hormone leptin to see how it affects preference for and intake of high‑fat foods after a period of abstaining. The team will measure leptin signaling and molecular changes in that pathway and test how changing activity in those neurons alters relapse‑like overeating. Most experiments are done in lab models to reveal the neural and molecular steps that could make this circuit insensitive to leptin after dieting. The goal is to identify targets that could eventually be used to reduce cravings and prevent weight regain.

Who could benefit from this research

Good fit: People with obesity who struggle with strong cravings for high‑fat or highly palatable foods and who commonly regain weight after dieting would be the most relevant group.

Not a fit: People whose weight issues are driven primarily by factors other than overeating of palatable foods, or those needing immediate clinical treatment, may not directly benefit from this basic‑science work in the short term.

Why it matters

Potential benefit: If successful, the work could point to new biological targets to reduce relapse to overeating and help people keep weight off after dieting.

How similar studies have performed: Previous animal studies have linked leptin and hypothalamic circuits to feeding behavior, but the specific leptin‑responsive lateral hypothalamus to vlPAG pathway and its role in post‑diet overeating is largely novel.

Where this research is happening

Blacksburg, United States

Researchers

About this research

  1. This is an active NIH-funded research project — typically early-stage science, not a clinical trial accepting patient enrollment.
  2. Some NIH-funded labs run parallel clinical studies or seek volunteers for related work. To check, contact the principal investigator or institution listed above.
  3. For full project details, budget, and progress reports, visit the official NIH RePORTER page below.
Last reviewed 2026-06-10 by the Find a Trial editorial team. Information on this page is for educational purposes and is not medical advice. Always consult qualified healthcare professionals about clinical trial participation.