Science & Technology

This molecule regulates fat burning in mice. – Science Inquirer

Boston – Obesity affects more than one-third of adults in the United States in relation to serious health problems such as cancer, diabetes and cardiovascular disease. Currently, there are few safe and effective non-surgical therapeutic interventions available to obese patients.

Now, an interdisciplinary team of researchers has demonstrated that a metabolic regulator called Them1 prevents intracellular fat burning by blocking access to fuel sources. The study, led by a microscope expert at the Beth Israel Deaconess Medical Center (BIDMC) and a metabolic expert at Weill Cornell Medicine and New York-Presbyterian, may contribute to the development of new types of obesity treatments.The team’s findings were released on June 9th Nature Communications..

To explain how the protein Them1 turns off heat production, BIDMC cell biology and microscopy experts Susan Hagen, PhD, is the research vice chair of BIDMC’s surgical department, Yue. Li and PhD are postdoctoral fellows in her lab. The effect of Them1 on laboratory-grown mouse brown adipocytes was observed using light and electron microscopy.

“These ones are interesting molecules,” Hagen said. “Inhibiting or blocking its expression increases metabolism and causes weight loss.”

Experiments have shown that when cells are stimulated to burn fat, chemical modifications cause the Them1 molecules to spread or spread throughout the cell. This frees the cell’s power plant, called mitochondria, and efficiently converts the cell’s fat storage into energy. However, when stimulation ceases, Them1 molecules are quickly reorganized into structures called biomolecular condensates. Located between mitochondria and the fat they use as fuel, the condensed Them1 molecule limits energy production.

“It turned out to be very interesting,” said Hagen, director of BIDMC’s core microscope and histology facility and associate professor of surgery at Harvard Medical School. “We asked other microscopy experts if they had seen anything like anomalous images found in stationary cells. Using very sophisticated electron microscopy techniques, we As far as I know, I was able to show for the first time what a bimolecular condensate looks like under an electron microscope. “

“This study describes a new mechanism that regulates metabolism,” said Vincent Astor of Weil Cornell Medicine, Head of Gastroenterology and Hepatology at Weil Cornell Medicine and New York Elders / Weil Cornell Medical Center. David Cohen, a professor of medicine, said. “Them1 hacks the energy pipeline and cuts off the fuel supply to the energy-burning mitochondria. This finding is obese because humans also have brown fat and produce more Them1 in cold conditions. It can have a stimulating effect on the treatment of obesity. “

Cohen and Hagen, members of the Harvard Gastroenterology Center, have been collaborators since 1983. The current study is partially supported by a five-year multi-PI grant from the National Institutes of Health, including collaborators with structural expertise. Biology at Emory University.

“This was the most fun I’ve ever had in science,” Hagen added. “By including multiple principal investigators with different expertise, we can do things that we can never do.”

Co-authors included BIDMC’s Yue Li, Samaksh Goyal, Lay-Hong Ang, and Mahnoor Baqai. Norihiro Imai, Haley T. Nichols, Weil Cornell’s Teeball I. Crisco. Brain R. Roberts, Matthew C. Tillman, Anne M. Roberts, Eric A. Altland of Emory University.

This study included the National Institutes of Health (R01 DK 103046, R01 DK0488730 and NIHT32 DK007533), Harvard Gastroenterological Center (P30 DK034854), and the National Institutes of Health’s Equipment Sharing Equipment Grant Program for High Pressure Freezers (S10 OD019988-01). , Pinnacle Research Award from AAASLD Foundation, Weill Cornell Department of Medicine Pre-Career Award, American Heart Association Postdoctoral Fellowship, and Research Science Institute / Center for Excellence in Education Summer Research Fellowship.

The author has not declared competing interests.

About Beth Israel Deaconess Medical Center
Beth Israel Deaconess Medical Center is a patient care, education, and research affiliate of Harvard Medical School and consistently ranked as a national leader among independent hospitals funded by the National Institutes of Health. It is attached. BIDMC is the official Boston Red Sox hospital. For more information, please visit:

Beth Israel Deaconess Medical Center is part of Beth Israel Lahey Health. It is a healthcare system that brings together academic and educational hospitals, community hospitals, specialty hospitals, more than 4,000 doctors and 35,000 employees on a common mission to increase access to superior health care. Advance the science and practice of medicine through breakthrough research and education.

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This molecule regulates fat burning in mice. – Science Inquirer This molecule regulates fat burning in mice. – Science Inquirer

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