Researchers at WashU Medicine have uncovered a potent mechanism originating in the brain that results in the complete depletion of body fat without any reduction in food intake.
The team, spearheaded by Eric L. Scheller from the Department of Medicine, Xiao Zhang from the University of Pennsylvania, and Sri Panicker from Scheller’s lab, was drawn to investigate a unique population of fat cells situated deep within the skeleton.
“Roughly 70% of our bone marrow is comprised of fat that is resistant to modification through diet or physical activity,” states the study’s lead author, Scheller. “We sought to understand the reason behind this resistance.”
The investigators discerned that these specific cells, termed constitutive bone marrow adipocytes, exhibit high expression levels of proteins that actively suppress the breakdown of fat. This characteristic renders them resistant to typical fat loss during daily life. “We refer to these as ‘stable adipocytes’,” mentioned Zhang. In mice, prolonged administration of leptin, a hormone, directly into the brain was successful in unlocking these stable adipocytes, thereby inducing a state of low glucose and insulin levels throughout the body. This metabolic shift deactivated the inhibitors of fat breakdown, leading to the complete eradication of body fat within a few days, despite the mice maintaining their normal eating habits.
This process is so potent that scientists advise caution against its application in humans until a more thorough understanding is achieved. Stable adipocytes are found in locations such as bone marrow, the hands and feet, and surrounding critical glands. In cases of severe wasting diseases, the fat loss from these cells correlates with bone fractures and a diminished quality of life. Scheller’s team aims to prevent this loss, preserving the health of patients suffering from severe wasting conditions, by pinpointing the mechanisms behind this stable fat loss. Conversely, methods designed to coax fat loss from these stubborn adipocytes could inform the development of forthcoming obesity treatments.
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