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Researchers discover new way fat cells sense fatty acids to adapt their metabolism

Findings could inform the development of novel therapies for metabolic diseases

5 August 2025

Researchers from the University of Birmingham have uncovered a completely new mechanism by which fat cells (adipocytes) control how they store and release fat.

Published today in Nature Chemical Biology, their study shows that a receptor previously known to respond to dietary fats can also work inside the cell, next to fat storage compartments called lipid droplets.

The results of the study change our understanding of how fat metabolism is regulated and could lead to new strategies in treating obesity, diabetes and other metabolic diseases.

The study is a collaboration with scientists at the Universities of Copenhagen, Glasgow and Montréal. The work was partially carried out at and supported by the Centre of Membrane Proteins and Receptors (COMPARE) and the National Institute for Health and Care Research (NIHR) Birmingham Biomedical Research Centre.

This discovery could change the way we think about drug development for metabolic diseases, offering more precise ways to regulate fat metabolism.

Professor Davide Calebiro, Department of Metabolism and Systems Science, University of Birmingham

Fat cells are specialised cells that store energy in the form of fat. When our body needs energy, fat cells release fatty acids in a process called lipolysis. Lipolysis is a delicate process; too much can lead to excess fat in the blood (a risk factor for diabetes and heart disease), while too little can make it difficult for the body to access stored energy.

Receptors like the one the researchers investigated (known as free fatty acid receptor 4 or FFA4), are part of the large family of G protein-coupled receptors (GPCRs). These receptors are found in cell membranes and play a crucial role in cell signalling. Traditionally, these receptors were thought to only be active on the cell surface, responding to signals from outside the cell.

However, the researchers found that FFA4 receptors are mainly located inside fat cells, on internal membranes near lipid droplets. When fat is broken down, the released fatty acids immediately activate these internal receptors. This triggers a local “brake” on fat breakdown, creating a fast, self-regulating feedback loop at each individual lipid droplet.

This ‘intracrine’ signalling (meaning the cell uses its own internally generated signal) is a completely new concept for metabolite-sensing receptors like FFA4.

We were surprised to find that FFA4 works like a built-in sensor inside fat cells, controlling fat breakdown in real time. This discovery reveals that fat cells have a highly localised way to control fat release, which could be crucial for maintaining healthy metabolism.

Dr Shannon O’Brien, Research Fellow, University of Birmingham

Understanding this mechanism opens up new possibilities for designing innovative therapies that specifically target these intracellular FFA4 receptors. These treatments could help regulate fat storage and release in a more precise way, which could be particularly beneficial for people with metabolic diseases such as type 2 diabetes or obesity.

Davide Calebiro, Professor of Molecular Endocrinology at the University of Birmingham and senior author of the study, said: “This discovery not only describes a completely novel mechanism of ‘intracrine’ signalling, which could be relevant for other metabolically relevant receptors, but could also lead to the development of a new generation of more effective and better tolerated therapies for metabolic diseases”.

Notes for editors

Notes for editors

For media enquiries please contact Tim Mayo or Holly Young, Press Office, University of Birmingham, tel: +44 (0)7815 607 157.

University of Birmingham

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  • University of Birmingham
  • University Hospitals Birmingham NHS Foundation Trust
  • Birmingham Women's and Children's Hospitals NHS Foundation Trust
  • Aston University
  • The Royal Orthopaedic Hospital NHS Foundation Trust
  • Sandwell and West Birmingham Hospitals NHS Trust
  • Health Innovation West Midlands
  • Birmingham and Solihull Mental Health NHS Foundation Trust
  • Birmingham Community Healthcare NHS Foundation Trust

About the National Institute for Health and Care Research

The mission of the National Institute for Health and Care Research (NIHR) is to improve the health and wealth of the nation through research. We do this by:

  • Funding high quality, timely research that benefits the NHS, public health and social care;
  • Investing in world-class expertise, facilities and a skilled delivery workforce to translate discoveries into improved treatments and services;
  • Partnering with patients, service users, carers and communities, improving the relevance, quality and impact of our research;
  • Attracting, training and supporting the best researchers to tackle complex health and social care challenges;
  • Collaborating with other public funders, charities and industry to help shape a cohesive and globally competitive research system;
  • Funding applied global health research and training to meet the needs of the poorest people in low and middle income countries.

NIHR is funded by the Department of Health and Social Care. Its work in low and middle income countries is principally funded through UK international development funding from the UK government.

This study has been delivered through the National Institute for Health and Care Research (NIHR) Birmingham Biomedical Research Centre (BRC). The views expressed are those of the authors and not necessarily those of the NIHR or the Department of Health and Social Care.

The NIHR Birmingham Biomedical Research Centre (BRC) is part of the NIHR and hosted by University Hospitals Birmingham NHS Foundation Trust (UHBFT) in partnership with the University of Birmingham (UoB). The BRC’s research programme focuses on inflammation and the diagnosis, prevention and treatment of its associated long-term illnesses.

Featured staff

  • Professor Davide Calebiro

    Head of the Department of Metabolism and Systems Science

    Staff Profile for Professor Davide Calebiro, Professor of Molecular Endocrinology and Wellcome Senior Research Fellow at the Department of Metabolism and Systems Science at the University of Birmingham.

    Phone: +44 (0)121 414 3928
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