PhD defence: Ibrahim AlZaim

On Monday 28 September at 13:00, Ibrahim AlZaim defends his PhD dissertation entitled “The Genetic and Epigenetic Determinants of Adipose Tissue Vascular Dysfunction in Human Obesity”.

Adipose tissue undergoes extensive changes during obesity. Among other things, the tissue becomes inflamed and progressively loses its normal function. Research has tradtionally focused on fat cells and immune cells, while blood vessels within adipose tissue have received considerably less attention.

In his PhD project, Ibrahim AlZaim investigated the blood vessels of human adipose tissue at the single-nucleus resolution. By combining advanced sequencing technologies with studies of human tissue and validation in cell and animal models, the project mapped the different vascular cell populations and examined how they change during obesity and type 2 diabetes.

The findings reveal that the blood vessels in adipose tissue comprise more heterogeneous cell states than previously appreciated. The project further shows that obesity causes extensive changes in these cells and that some of these responses differ between males and females.

One part of the project focused specifically on endothelial cells, which form the inner lining of blood vessels. The project characterized an immunomodulatory endothelial cell state in which these cells respond to inflammatory signals and acquire properties normally associated with the immune system. These cells become more abundant in metabolically unhealthy obesity and are associated with insulin resistance, while their abundance decreases following weight loss. 

The experiments further point to the inflammatory molecule interferon-gamma as a signal capable of driving this endothelial state. When interferon-gamma signaling was specifically inhibited in endothelial cells in a mouse model of obesity, several of the harmful changes occurring in the adipose tissue were reduced.

Together, the PhD project demonstrates that blood vessels are not simply passive victims of obesity. Instead, vascular cells actively respond to their environment and can themselves contribute to inflammation and the remodeling of the adipose tissue. The findings provide a new perspective on the role of blood vessels in metabolic diseases and suggest that the vasculature could eventually provide new opportunities for therapeutic intervention.

The summary is written by the PhD student. 

The defence is public and takes place in Universitetsbyen 1790-329, Aarhus University. Please see the press release for more information.

Contact

PhD student Ibrahim AlZaim
E-mail: ima@biomed.au.dk
Phone: +45 52797075

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