About 16% of adults worldwide (2.5 billion people) are obese, and 37 million children under the age of five are overweight; the prevalence of both conditions has more than doubled between 1990 and today.
It is estimated that 64% of Israelis are overweight or obese, according to the World Health Organization, which defines overweight as having a body-mass index greater than or equal to 25; and obesity as having a BMI greater than or equal to 30.
Once considered a problem of advanced countries, overweight and obesity are also on the rise in middle-income and poor countries, including those in Africa and Asia.
Now, a new international study led by scientists from Ben-Gurion University of the Negev (BGU) in Beersheba has characterized the populations of fat cells in various tissues in the human body. Using innovative technology, the researchers were able to identify for the first time unique subpopulations of fat cells, with more complex predicted functions than previously known, and even identified differences among human fat tissues in intercellular communication.
The researchers studied the diversity of fat cells in subcutaneous and intra-abdominal (visceral) fat tissues in humans. Their findings provide a basis for further research to promote personalized medicine in obesity.
The study has just been published in the prestigious journal Nature Genetics by a research team led by Profs. Esti Yeger-Lotem and Assaf Rudich from the clinical biochemistry and pharmacology department in BGU’s Faculty of Health, who studied the biology of fat cells, in collaboration with Prof. Naomi Habib from the Hebrew University of Jerusalem, Profs. Matthias Bluher, Antje Korner and Martin Gericke from the University of Leipzig, Germany, and Prof. Rinki Murphy from the University of Auckland, New Zealand.
IN THE last 30 years, scientists’ views of fat tissues and cells have transformed from being “boring” tissue whose sole purpose was to store excess energy in the form of fat. It used to be thought that fat is fat, and that all the cells are of the same type. But it isn’t so, and the differences affect the patient. The study is part of an international effort, the Human Cell Atlas Project, to generate a comprehensive map or atlases of all types and subtypes of cells that make up the human body, in partnership with many other labs around the world that analyzed fat removed with permission from adults during surgery.
The team focused on adipose, which is connective tissue that extends throughout the body and is found under the skin (subcutaneous fat), between the internal organs (visceral fat) and even in the inner cavities of bones that produces and secretes hundreds of proteins and other substances into the bloodstream.
The aim was to better understand what these special cells do and how they cause disease. “If you find specific cells, you can suit them to patients and treat them individually,” Yeger-Lotem told The Jerusalem Post. “There are people who lose weight and then gain again, so it would be beneficial if we could predict this.”
How study was carried out
THE STUDY used innovative technology that maps RNA molecules which are the basis for translating the genome into proteins. The technology is based on attaching a unique single-cell-specific “barcode” to RNA molecules originating from each cell. Thousands of cells that make up the tissue are thereby barcoded simultaneously, enabling the detection of cells containing similar subsets of RNA molecules that belong to the same cell type, and cells with distinct subsets of RNA molecules that belong to different, uncharacterized sub-types. They regulate a wide variety of processes through intercellular communication within the fat tissue and with the brain, blood vessels, liver, and pancreas tissues.
It became clear that adipose is not a single tissue. Instead, fat tissues in separate locations in the body – for example, under the skin, or inside the abdominal cavity and around the internal organs (visceral fat) – function differently and have a diverse impact on health and disease. Visceral adipose tissue develops in obesity as a more inflammatory tissue, containing more immune system cells whose communication with fat cells contributes to the metabolic complications (diabetes and fatty liver) and cardiovascular ones of obesity.
“The diversity of fat cells in the different fat tissues in humans is more complex, interesting, and surprising than we previously thought,” Yeger-Lotem explained.
“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). After we found them computationally, we were also able to see them under the microscope.”
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.
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, Rudich said.
“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.”
