Obesity continues to be a major public health concern, with nearly 40% of Americans affected, leading to an increased risk of conditions such as high blood pressure, diabetes, stroke, heart disease, and certain cancers, according to the CDC. A new study from the University of Delaware (UD) aims to explore the genetic factors behind obesity by examining how diet influences gene expression in fat tissue.
Ibra Fancher, assistant professor of kinesiology and applied physiology at UD’s College of Health Sciences, led the research, which reveals significant differences in gene expression within adipose tissue—commonly known as body fat. Once thought of solely as a storage site for fat, adipose tissue is now recognized as a critical endocrine organ. Dysfunction in this tissue is closely linked to cardiovascular and metabolic diseases.
Published in Physiological Genomics, the study used an animal model to investigate how diet affects gene expression in adipose tissue. One group of animals was fed a high-fat, high-calorie Western-style diet, while the other group consumed a standard chow diet for over a year.
“We expected to see substantial changes in fat tissue, and indeed, the adipose depots in the high-fat group were much different, showing significant changes linked to poor diet and obesity,” Fancher said.
Key Findings
Funded by a federal grant from the National Institutes of Health (NIH) through UD’s Center of Biomedical Research Excellence (COBRE) in Cardiovascular Health, the study found that more than 300 genes were differentially expressed in subcutaneous adipose tissue (SAT), which is considered a less harmful form of fat. In contrast, nearly 700 genes were found to be differentially expressed in visceral adipose tissue (VAT), which surrounds vital organs and is known to significantly increase health risks.
“The contrast between VAT and SAT is striking. The expansion of visceral fat, along with its role in inflammation and metabolic diseases, is particularly severe,” Fancher noted. “This study underscores the impact of obesity, which often results from poor diet and inactivity, on specific adipose tissues. This makes these tissues a promising target for interventions aimed at protecting other systems in the body.”
The study also identified four key genes related to metabolism, calcium handling, and inflammation that could warrant further investigation. Fancher and his team are exploring whether these genes can be targeted with existing drugs or used to develop new treatments aimed at improving adipose tissue function in obesity.
Innovative Approach
Fancher collaborated with Bruce Kingham, director of UD’s Sequencing and Genotyping Center at the Delaware Biotechnology Institute, and Shawn Polson, director of the Bioinformatics Data Science Core at UD’s Center for Bioinformatics and Computational Biology. Their combined expertise in RNA sequencing and bioinformatics played a pivotal role in identifying genes and pathways related to obesity.
“Our core facilities provide cutting-edge technologies and the necessary expertise for RNA sequencing and bioinformatics, which were essential for this research,” Polson said. “Through our analysis, we were able to pinpoint obesity-related genes and pathways that varied significantly between VAT and SAT.”
The study also benefited from the contributions of Malak Alradi, a third-year doctoral student in molecular biology and genetics. Alradi helped organize the genes into pathways to better understand their biological relevance. “Before starting this research, I thought fat was the same throughout the body. However, after analyzing the RNA sequencing data, I realized that VAT is far more affected by obesity than SAT,” Alradi explained. “Our approach illustrates how interconnected these biological processes are and why targeting specific pathways could be pivotal for treating obesity.”
Statistical analysis confirmed the key findings, reinforcing the novelty and significance of the genes identified in the study.
Next Steps
Building on these results, Fancher plans to extend his research to human adipose tissue. Collaborating with Dr. Caitlin Halbert, director of bariatric surgery at ChristianaCare, Fancher will investigate whether these findings hold true for human samples.
Fancher also noted that obesity may affect men and women differently, suggesting the possibility of sex-based differences in how genes are expressed in adipose tissue. “Obesity influences the sexes differently, so I wouldn’t be surprised if we find variations between men and women,” Fancher said. “Recognizing these differences is crucial for developing more personalized and targeted interventions.”
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