York-led research results in breakthrough discovery for obesity-related health issues

Blood vessels

New research led by York University Faculty of Health Professor Tara Haas could be considered a breakthrough discovery in understanding obesity-associated events that worsen an individual’s health.

Tara Haas
Tara Haas

Haas and a multidisciplinary team of scientists investigated the cause of a vascular dysfunction that links obesity with undesirable health outcomes, such as inflammation and diabetes, and made a novel finding that blood vessels may participate in the control of whole-body energy balance.

Researchers, including York Professors Emilie Roudier, Rolando Ceddia and Christopher Perry, studied a process of the vascular system called angiogenesis and how its repression in the body relates to the unhealthy expansion of adipose (fat) tissue.

Angiogenesis, which is the new formation of tiny blood vessels called capillaries, helps to maintain normal healthy functions in tissue, particularly when that tissue enlarges. However, when adipose tissue expands as it stores excess fat, angiogenesis is repressed and new capillaries fail to grow.

“It is not clear why exactly new capillaries fail to form in obesity,” said Haas.

Previous research led by Haas, a professor in the School of Kinesiology & Health Science, found the levels of a particular protein called “FoxO1” increase in endothelial cells (the main cells that comprise capillaries) during obesity.

“What we know is that a protein called FoxO1 (short for Forkhead box O) is present in the cells that line the inside of blood vessels, and that it can stop the development of new capillaries. FoxO1 controls how cells spend their energy, and it can force them to go into a resting state. During obesity, the levels of FoxO1 increase in capillary endothelial cells. Therefore, it may be possible that FoxO1 prevents new blood vessels from growing in the fat tissues of obese individuals,” she said.

An image of blood vessels

In the study published Dec. 4 in the online journal ELife, researchers investigated whether the FoxO1 protein is the reason why capillaries fail to grow in the adipose tissue of obese individuals.

The team inhibited the production of FoxO1 protein, and monitored the behaviour of capillary endothelial cells and the resultant influences of these changes on the expansion of adipose tissue. What they found was that lowering FoxO1 levels promoted angiogenesis and caused a healthier adipose tissue – in particular, with a high-fat diet. Remarkably, lower levels of endothelial cell FoxO1 also led to an increase in the use of glucose, and less weight gain, despite consuming a diet high in fat.

“Our study showed that removing FoxO1 made endothelial cells ‘hyper-active,’ ” said Haas, adding that this enabled the formation of a lot of new blood vessels in the fat tissue, and it also helped to use excess energy.

The results show that targeting FoxO1 in the cells that line capillaries helps new blood vessels to grow, and that this could mitigate the health problems that arise with obesity, such as high levels of blood glucose (diabetes) and circulating fats.

Martina Rudnicki
Martina Rudnicki

“Our findings provide mechanistic insights into how lowering FoxO1 levels in endothelial cells acts to stimulate the growth of vessels in the adipose tissue during obesity, and also raise the novel concept that blood vessels may participate in the control of whole-body energy balance,” said Martina Rudnicki, a postdoctoral fellow in the Haas lab who was the primary person conducting the research.

Rudnicki was invited to present these results at the international conference called Metabolism in Cancer and Stromal Cells (2nd edition), held in Belgium last month. She was honoured with first prize for her talk.

While these results are promising, more research is needed to investigate the optimal way to target these cellular processes to obtain positive health outcomes.

The research was funded by a Canadian Institutes of Health Research grant to Haas and Roudier.