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Fat functions as an essential building block of the human body, serving not only as an energy storage and release mechanism, but also plays a pivotal role in hormonal regulation and immune function.
In recent years, the increasing prevalence of metabolic disorders such as heart disease, hypertension and diabetes has led to intensive scientific research into adipocyte properties and functions. This has yielded a wealth of information about the complex workings of these cells.
But fat cells and their metabolic activity are only part of the story.
Fat-filled lipid droplets, tiny globules of fat many times smaller than fat cells, are a subject of increasing scientific interest.found internal Due to the many different cell types, these lipid particles have long been poorly understood. Although studies are beginning to reveal that these droplets are involved in metabolic function and cell protection, little is known about the physical properties of fat.
Now, beyond biochemistry, researchers at the University of Pennsylvania School of Engineering and Applied Sciences present a groundbreaking study of the physics of these droplets, demonstrating that these droplets have potential for the nucleus of cells. revealed to be a serious threat. In a recently published paper, cell biology journalThey were the first researchers to discover the amazing ability of fat-filled lipid droplets to dent and pierce the nucleus, the organelle that contains and controls the cell’s cells. DNA.
The danger of their detection is high. Nuclear disruption can lead to increased DNA damage, a hallmark of many diseases, including cancer.
The research was led by Dennis E. Disher, Professor Robert D. Bent, and Dr. Irena Ivanovska of the Department of Chemical and Biomolecular Engineering. Dr. Michael Tobin, Research Fellow in the Laboratory of Molecular and Cellular Biophysics, University of Pennsylvania. Candidate of Department of Biotechnology.
“Intuitively, people think of fat as soft,” says Disher. “And at the cellular level it is. But at droplets of this small size (just a few microns instead of the hundreds of microns of mature fat cells), they become less soft. bend very sharply, this changes the physical properties inside the cell, it can be deformed, it can be damaged, it can burst.”
“Imagine,” added Ivanowska. “You’re trying to pop a balloon with your fist. Impossible. You can transform a balloon, but you can’t puncture it. Now imagine you’re trying to pop it with a pen. But it’s the difference between fat cells and cells that contain tiny lipid droplets in the body.It’s not a metabolic difference, it’s a fundamental physical difference.”
The research team’s study reconstructs scientific research on fat and emphasizes that fat’s role in the body is much more than just a number on the scale.
“This is not the norm for fat,” says Tobin. “It’s about how fat works on a scale smaller than the cell and poses a physical risk to the cellular components, even at the DNA level.”
The research team’s work builds on a decade of fundamental research, including Ivanovska’s major contribution to the behavior of nucleoproteins that endow the nucleus with protective structural properties. These proteins dynamically change levels in response to the mechanical environment, providing what the nucleus needs to maintain its integrity.
“There is a continuous process of repairing DNA damage inside the cell,” says Ivanowska. “For this to happen, the nucleus needs to have enough DNA repair proteins. cancer cells may develop.”
Cells live in a dynamic physical and mechanical environment where things can go wrong and can actually cause problems. But there is also an army of molecular helpers constantly working to maintain and repair it.
“The problem is when the nucleus is compromised by toxins, overexposure to UV light, or fat-filled lipid droplets,” says Disher. In that case, DNA damage is very likely, with health consequences. “
Reference: “Small lipid droplets are hard enough to dent the nucleus, dilute the layers, and cause rupture.” Irena L. Ivanovska, Michael P. Tobin, Tianyi Bai, Lawrence J. Dooling, Dennis E. Discher, 2023 5 22nd of the month, cell biology journal.
DOI: 10.1083/jcb.202208123
This research was supported by the National Science Foundation, Human Frontier Science Program, National Institutes of Healthand the Pennsylvania Department of Health.