A groundbreaking international study led by scientists from Ben-Gurion University of the Negev has provided unprecedented insights into the diverse populations of fat cells across different fat tissues in the human body. Using cutting-edge technology, the researchers identified unique subpopulations of fat cells, revealing previously unknown complexities in their functions and intercellular communication.
Published in Nature Genetics, the findings offer a significant leap forward in understanding fat tissue biology, with potential applications for personalized obesity treatments.
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The research was led by Prof. Esti Yeger-Lotem and Prof. Assaf Rudich from Ben-Gurion University’s Faculty of Health Sciences, in collaboration with Prof. Naomi Habib from the Hebrew University of Jerusalem, Profs. Matthias Blüher, Antje Körner, and Martin Gericke from the University of Leipzig, Germany, and Prof. Rinki Murphy from the University of Auckland, New Zealand. Together, they mapped the diversity of fat cells in subcutaneous fat (beneath the skin) and visceral fat (around internal organs), uncovering key differences in their biological roles.
This study is part of the Human Cell Atlas Project, a global initiative aimed at creating a comprehensive map of all human cell types. By contributing to this effort, the researchers have laid the foundation for future studies that could revolutionize our understanding of fat metabolism, obesity, and related diseases, ultimately advancing precision medicine in metabolic health.
“The diversity of fat cells in the different fat tissues in humans is more complex, interesting, and surprising than we previously thought. For example, in addition to the ‘classical’ fat (adipocyte) cells, we found subpopulations of adipocytes, characterized here for the first time, that express RNA molecules indicating unique functions, such as regulation of inflammatory processes, blood vessel formation, extracellular protein deposition, and scarring (fibrosis),” explained Prof. Yeger-Lotem. “After we found them computationally, we were also able to see them under the microscope. We initially thought that these unique cells were created from the classical cells by ‘adopting’ additional, unique functions, but we discovered that the differentiation pathway is actually the opposite: the unique fat cells seem to “lose” their unique functions to become classical fat cells.”
Searching for the source of the differences between subcutaneous and visceral fat, the researchers found that most of the fat cell subpopulations were similar between subcutaneous and intra-abdominal fat. Nevertheless, significant, albeit more subtle, differences were identified between fat cells from the two tissues. For example, intercellular communication in the two tissues differs: fat cells in the intra-abdominal tissue express genes indicating more active communication with immune system cells within the tissue and are involved in pro-inflammatory processes. In contrast, in subcutaneous fat, fat cells communicate more with each other and participate in anti-inflammatory processes. In addition, one of the unique types of fat cells, discovered for the first time in this study, appeared only in the intra-abdominal tissue.
“The new insights into the cellular composition and function of human fat tissues provide a basis for further applied research aimed at promoting personalized medicine in obesity,” explains Prof. Rudich. “We found that the prevalence of the unique fat cells we identified was related to the metabolic complications of obesity: their relative proportion in the tissue is higher the more severe the insulin resistance is. If it turns out that the prevalence of unique fat cells also predicts the degree of personal risk for future development of obesity complications, and/or can predict the individual response to treatment – the findings may have great significance in the pursuit of more personalized treatment for obesity. To this end, we are already working to develop tools that can bring our findings to clinical medicine, for example, developing microscopic examinations of fat tissue and identifying unique fat cells by a clinical pathologist.”
