"When we increased lipin in the muscle, the cells burned carbohydrates before fat. When lipin is absent, however, the cells burn fat before carbohydrates," explained Reue.

"We saw a different effect when lipin acted on fat tissue," she noted. "High levels of lipin promoted fat storage. Lipin deficiency prevented the cells from forming and storing fat."

In other words, the mice with excess lipin in their fat gained weight because their cells stored more fat. The mice with more lipin in their muscle grew obese because the gene repressed their metabolism, causing them to burn fewer calories than normal mice.

In contrast, Reue's study showed that lipin-deficient mice expended more energy to perform their daily activities. Because lipin moderates calorie use in muscle, its absence caused the mice to burn more calories to fulfill the same tasks as normal mice.

"Our study suggests that variations in lipin levels could determine a person's tendency to gain weight by influencing how their body stores and burns fat," explained Reue.

"Prior to our research, scientists typically viewed obesity and emaciation as opposite ends of the spectrum caused by changes in different genes," Reue said. "Yet lipin is a single gene that can regulate body-fat content from one extreme to the other. As a result, it may present a target for the treatment of human diseases related to both excess and insufficient fat."

In an unexpected finding, the study also discovered that lipin levels helped the fat cells metabolize glucose more efficiently, leading to lower blood-sugar levels. The obese mice with excess lipin in their fat tissue demonstrated even lower blood-sugar levels than normal mice with regular levels of lipin.

"Because obesity and lipodystrophy are both associated with insulin resistance and high blood suga
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Contact: Elaine Schmidt
eschmidt@mednet.ucla.edu
310-794-2272
University of California - Los Angeles
18-Jan-2005