How glycogen is linked to heat generation in fat cells

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Humans carry with them, often in abundance, at least two kinds of fatty tissue: white and brown. White fat cells are essentially inert containers for energy stored as a single large oily droplet. Brown fat cells are more complex, containing multiple smaller droplets mixed with dark-colored mitochondria – cell organelles that give them their color and are the “engines” that convert the fat droplets into heat and energy.

Some people also have “beige” fat cells, brown cells residing in white fat that can be activated for energy burning.

In recent years, there have been many efforts to find ways to increase the activity of brown or beige fat cells, to induce fat cells, called adipocytes, to burn energy and generate heat in the body. a process called thermogenesis as a way to treat obesity, type 2 diabetes and other conditions.

But the therapeutic potential of brown fat – and perhaps beige fat cells – has been hampered by the complexity of the processes involved. It was not until 2009 that the existence of active brown fat cells in healthy adults was confirmed; previously, it was believed that they were only common in newborns.

In a new study, published online on October 27, 2021 in Nature , an international team of researchers led by senior author Alan Saltiel, PhD, director of the Institute for Diabetes and Metabolic Health at the University of California, San Diego School of Medicine, describes how energy expenditure and production heat are regulated in obesity by a hitherto unknown cell cell. path.

The human body breaks down the carbohydrates consumed into a type of sugar called glucose, which is the main source of fuel for cells. Unnecessary glucose is conditioned and stored as glycogen in liver and skeletal muscle cells, where it can be extracted and used quickly for sudden energy needs or to maintain blood sugar.

Unlike muscles and the liver, the role of glycogen in fat is a mystery. Researchers have found that glycogen does more than just store energy in fat cells. It provides a signal that produces a major change in the way energy is managed.

In this “surprise discovery”, Saltiel and his colleagues report that the browning of fat cells depends on their ability to make and then break down glycogen. The turnover of glycogen sends a signal that it is safe for the cell to “decouple” the production of ATP, the molecule that provides the energy that powers most cellular processes.

“Decoupling is a way to generate heat and, in doing so, to balance energy. This pathway ensures that only fat cells with enough energy to power the generation of heat are allowed to do so, ”Saltiel said.

The dramatic increase in obesity worldwide – 650 million people or 13%, a triple since 1975 – has underscored the importance of understanding how the human body balances energy intake and expenditure.

Glycogen regulates and promotes fat metabolism: the higher the levels, the more robust the metabolic processes, essentially burning fat faster with resulting weight loss in obese mice. In humans, the genes involved in these complex processes have been shown to be weaker in obese or weight gain patients, suggesting that the glycogen pathway is needed in fat cells to burn off excess weight. . The new findings, the authors wrote, suggest that modulating glycogen metabolism in fat cells may provide new approaches for weight loss and overall improvement in metabolic health.

Co-authors include: Omer Keinan, Joseph M. Valentine, Shannon M. Reilly, Mohammad Abu-Odeh, Julia H. Deluca, Benyamin Dadpey, Leslie Cho, and Austin Pan, all at UC San Diego; Haopeng Xiao and Edward T. Chouchani, Dana-Farber Cancer Institute and Harvard University; Sushil K. Mahata, VA San Diego Healthcare System and UC San Diego; Ruth T. Yu, Yang Dai, Michael Downes and Ronald M. Evans, Salk Institute; Christopher Liddle, University of Sydney, Australia; Aldons J. Lusis, UCLA; Markku Laakso, University of Eastern Finland; and Mikael Ryde’n, Karolinska Institutet.

Funding for this research came, in part, from the National Institutes of Health (grants 1R01 DK117850, 1R01 HL147883, F32DK124947, DK057978, DK120480, R01DK117551, R01DK125820, R01DK076906, P30 DK06309591) and the Association (1-12) 19 PDF-177, 1-19-JDF-012) the Claudia Adams Barr program, the Lavine Family Fund, and the National Cancer Center.


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