Developing a 3D non-animal obesity model

The Problem

Declared an epidemic by the World Health Organisation, obesity is now the fifth leading cause of death globally. In the UK alone, obesity affects one in four adults and one in five children.

Why is obesity such a concern? We store the energy from our diet as fat in our adipose tissue inside fat cells, or adipocytes. Obesity occurs when excessive body fat is stored, causing the adipose tissue to become dysfunctional and inflamed. Inflammation reduces oxygen levels, disrupting metabolism, and leading to other health problems. To develop treatments, we must understand the link between fat tissue dysfunction and changes in metabolism.

Current research often relies on animal ‘models’. In fact, animal use in metabolic research is on the rise. The animals, primarily rodents, undergo procedures which can cause them severe suffering.

A potential alternative is 2D in vitro models, but these models can’t fully replicate the complexities of human adipose tissue. There are also practical challenges to overcome; for example, fat cells float in the dishes used for cell culture after accumulating lipids.

The Project

Dr Contessi Negrini and his team are developing a 3D model of healthy and obese adipose tissue for use in metabolic research and drug and toxicity screening. These innovative models could offer a huge step forward in understanding and treating obesity.

The team are using plant-derived soft materials, known as hydrogels. These have been designed to mimic the intricate structure and functions of human fat, including its role in inflammation. Hydrogels are biocompatible, meaning they can safely interact with living tissue without causing harm. This allows the team to create a living model that closely replicates the complex conditions found in obese individuals.

Nicola’s team at Imperial College is working with Dr Vanessa Pellegrinelli’s team at the University of Cambridge. Nicola’s team will design the hydrogels and adipocyte cell culture protocols to create the 3D models; Vanessa’s team will then test the models using their expertise of adipose tissue and how adipocytes function in the lab.

The Potential

This proof-of-concept model will accurately mimic fat tissues in individuals living with obesity. By providing a realistic platform to study fat tissue, researchers will gain crucial insights into how obesity contributes to other health problems.

In the future, they hope to include other cell types, like immune cells. This will better mimic the inflammation that obese patients experience. The team’s long-term goal is to include this in a multi-organ system, like a ‘lab-on-a-chip’.

Ultimately, this research could revolutionise obesity treatment by providing a more accurate understanding of the disease and enabling the development of targeted therapies.