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A new understanding of how glucose makes you fat

Drs. make connection between glucose and fat
Drs. Keun Ryu (left) and W. Lee Kraus examined compartments inside cells that house NAD+ molecules to determine how they activate genes that make fat cells.

Glucose is the energy that fuels cells, and the body likes to store glucose for later use. But since too much glucose can contribute to obesity, scientists have long wanted to understand what happens within a cell to tip the balance.

To solve this riddle, researchers at UT Southwestern’s Cecil H. and Ida Green Center for Reproductive Biology Sciences examined specialized compartments inside the cell to reveal the role of a molecule termed NAD+ in turning on genes that make fat cells.

Some scientists believe that boosting the production of NAD+ – a molecule found in every cell of the body – may be tied to better health and to slowing down the aging process.

UT Southwestern biologists examined individual compartments inside cells that house NAD+ molecules to determine how they control genes that are essential to the fat-storing process. This knowledge that could help in a wide range of ailments, including metabolic disorders, neurodegenerative diseases, inflammation and aging, and cancer.

“This compartmentalization ends up having profound effects on gene expression in the nucleus, as well as metabolism in the cytoplasm, the jellylike substance outside the cell’s nucleus,” said Dr. W. Lee Kraus, senior author of the study in Science. “We found that these processes play key roles in fat cell differentiation and in cancer cells.”

Previous thinking in the field, Dr. Kraus said, was that NAD+ was evenly distributed throughout cells and moved freely between different subcellular compartments.

“We showed that NAD+ is actually compartmentalized – there are separate nuclear and cytoplasmic pools of NAD+ whose levels change under certain cellular conditions,” explained Dr. Kraus, Director of the Green Center and Professor of Obstetrics and Gynecology, and Pharmacology.

Accounting for the levels of NAD+ biosynthesis separately rather than in their totality helped increase the understanding of the biology involved, said first author Dr. Keun Ryu, a postdoctoral researcher in Obstetrics and Gynecology.

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