Active Diabetes, Hormones & Metabolism NIHR-supported project Lungs & Breathing

A novel paradigm of intracrine fatty acid receptor signalling at lipid droplets: implications for adipocyte physiology and metabolic disease

Funder NIHR (part of DHSC)
Recipient organisation NIHR Birmingham Biomedical Research Centre
NIHR support Recorded as supported by this research centre
Period Feb 2025 — Jan 2028

In plain English

AI plain-English summary

Inside fat cells, fatty acids are stored in microscopic droplets, and this project investigates how two specific receptors on those droplets control the release of that fat. Obesity affects over 650 million people worldwide and is projected to cost over US$1 trillion by 2025. The problem is that when fat accumulates excessively, it raises the risk of heart attacks, strokes, insulin resistance, diabetes, and liver inflammation. Current therapies for these metabolic disorders are limited because scientists do not fully understand the fundamental cellular machinery that governs how fat cells store and release fatty acids. This project focuses on two G protein-coupled receptors, FFA2 and FFA4, which are activated by fatty acids inside adipose cells and are already being considered as potential drug targets. If this research succeeds, it will reveal novel molecular mechanisms controlling fat storage and release. That deeper understanding could lead to more targeted therapies for obesity-related metabolic diseases, potentially improving treatments for diabetes and cardiovascular conditions. This is fundamental science—it does not promise an immediate cure, but it fills a critical gap in knowledge about how fat cells work at the molecular level, which is a necessary step before better drugs can be designed.

View original technical description
Obesity is a growing global health concern, affecting more than 650 million people worldwide and predicted to cost over US$ 1 trillion by 2025. The adipose tissue serves as an important storage of energy in the form of fatty acids contained in fat. Inside adipose cells, fatty acids are stored in specialised cellular structures known as ‘lipid droplets’, from where they are released during fasting in a process termed lipolysis. When someone develops obesity, their body stores an excessive amount of fat, leading to health problems. One major issue is that fat accumulation significantly increases the risk of cardiovascular diseases such as heart attacks and strokes. Additionally, it can lead to insulin resistance, causing diabetes, and inflammation, affecting the function of several organs such as the liver. This project addresses the urgent need to better understand the fundamental cellular and molecular mechanisms that control the storage and release of fatty acids in order to develop improved therapies for obesity-related metabolic disorders. In particular, we focus on the free fatty acid receptors 2 and 4 (FFA2/4), two G protein-coupled receptors (GPCRs) activated by fatty acids in adipose cells, which are under consideration as potential drug targets for obesity-related metabolic disorders. Our research holds promise for identifying novel molecular mechanisms involved in the control of fatty acid storage and release in physiology and disease, with potential implications for the therapy of obesity-related metabolic disorders.

Researchers

Davide Calebiro (Principal Investigator)

Related Research

Grants with similar aims, by meaning.

Long Chain Fatty Acid Mediated Communication Between Metabolism and Inflammation as a Potential Therapeutic Target for Type 2 Diabetes
Physiological functions and mechanisms of action of the short chain fatty acid receptor FFAR2 dissected using allosteric and biased activating ligands
Characterisation of the role of endoplasmic reticulum stress signalling in the obesity-driven inflammatory drift in adipose tissue
New paradigm of GPCR signalling at intracellular sites in metabolic diseases
Tackling type 2 diabetes by reducing the chronic release of toxic amounts of fatty acids from adipocytes

Original classification

Women's Metabolic Health

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