How a brain receptor called MC4R may cause antipsychotic-related weight gain and diabetes

Hypothalamic MC4Rs and Antipsychotic Drug-Induced Metabolic Syndrome

['FUNDING_R01'] · UT SOUTHWESTERN MEDICAL CENTER · NIH-11289426

Researchers are looking at whether changes to a brain receptor called MC4R explain why people taking antipsychotic medications often gain weight and develop diabetes.

Quick facts

Phase['FUNDING_R01']
Study typeNih_funding
SexAll
SponsorUT SOUTHWESTERN MEDICAL CENTER (nih funded)
Locations1 site (DALLAS, UNITED STATES)
Trial IDNIH-11289426 on ClinicalTrials.gov

What this research studies

The team created mouse models that mimic the weight gain and metabolic problems caused by common antipsychotics (olanzapine and risperidone). They found that increased eating drives the weight gain and that antipsychotic treatment lowers Mc4r levels in the hypothalamus before weight rises. Electrophysiology experiments showed these drugs acutely inhibit MC4R-expressing neurons through a postsynaptic potassium conductance. The current work will dig deeper into how antipsychotics disrupt MC4R signaling in mice and test approaches that could point to ways to prevent these metabolic side effects in patients.

Who could benefit from this research

Good fit: Adults taking antipsychotic drugs such as olanzapine or risperidone who are concerned about weight gain or metabolic changes are the most relevant patients for this research.

Not a fit: People not taking antipsychotic medications or whose metabolic problems have other causes are unlikely to benefit directly from this specific work.

Why it matters

Potential benefit: Could lead to strategies or treatments that prevent or reduce antipsychotic-related weight gain and diabetes risk for people on these medications.

How similar studies have performed: Prior studies have linked MC4R to appetite and obesity, and this project builds on new mouse model work that newly connects MC4R dysfunction to antipsychotic-induced metabolic syndrome.

Where this research is happening

DALLAS, 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.

View on NIH RePORTER →

Conditions: Adult-Onset Diabetes Mellitus

Last reviewed 2026-05-15 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.