Investigating obesity and cardiovascular disease

Manchester research is investigating the links between a specific type of fat called perivascular adipose tissue (PVAT) and cardiovascular disease in obesity.

Cardiovascular disease is the leading cause of death worldwide, especially in low- and middle-income countries. It is highly prevalent in people over 60, the fastest-growing age group worldwide, but now more young and middle-aged adults are now at risk because of rising rates of obesity.

Obese patients are at a high risk of developing multi-morbidities, which means they may develop more than one health condition including high blood pressure, high cholesterol or type-2 diabetes, all of which will contribute to reduced life expectancy.

Multi-morbidities in people with cardiovascular disease make approaches to treatment more complicated, and understanding how these conditions progress is key to developing successful new treatments. These conditions can lead to inflammation in the body, which may damage the heart and blood vessels over time.

Adipose tissue: friend turned foe

Scientists at The University of Manchester are studying how a special kind of fat called perivascular adipose tissue (PVAT), which surrounds blood vessels, might be connected to cardiovascular disease in obesity.

In health, PVAT releases factors that play a beneficial role in controlling blood pressure, glucose and insulin. However, in obesity, the fat cells in PVAT grow too large and don't get enough oxygen, resulting in chronic inflammation.

PVAT stops releasing these beneficial factors and instead releases factors that increase blood pressure and glucose, contributing to the development of high blood pressure and diabetes.

Management of multi-morbidities

The first line of treatment for obesity-related diseases is diet and exercise; however, this is difficult for many, and often those who lose weight on a diet will put that weight back on and more.

"The mechanistic links between obesity and cardiometabolic diseases is poorly understood because the solution is obvious, right? 'Just go on a diet'," says Dr Sophie Saxton, who is carrying out research into PVAT.

"But we all know that weight loss is incredibly difficult, and keeping the weight off is a continuous battle. So, there is a desperate need to fully understand how obesity causes these diseases, so that we can develop better treatments."

Even new weight loss drugs such as Ozempic, Wegovy and Mounjaro don't work for everyone, and can have unpleasant side effects. Plus, once people stop taking those drugs, many will regain the weight.

By understanding how fat, inflammation and the immune system interact, researchers hope to explain how these conditions develop and interact at the molecular level, offering new insights into managing and treating multi-morbidity diseases.

Research into PVAT and its role in hypertension and cardiovascular disease has the potential to make a significant global impact by advancing discovery of new therapeutic targets for obesity-related diseases, improving diagnosis and helping to detect or predict cardiovascular risk before symptoms appear.