Molecular Switch Behind Liver Disease Development Identified

Molecular switch transducin beta-like (TBL) 1, appears to be a common feature in the development of fatty liver disease, say scientists. The discovery made in mice is consistent with data from human patients, suggesting that it may provide an underlying explanation for the development of fatty liver in people with obesity and metabolic syndrome. The culprit is the reduced concentration of a little-known transcriptional co-factor known as transducin beta-like (TBL) 1, according to the researchers.

"We haven't entirely solved it yet, but we've seen that a lower abundance of TBL1 is common to multiple mouse models," said Stephan Herzig of DKFZ-ZMBH Alliance in Germany.

"Most importantly, in human livers, the more fat there is the lower this transcriptional co-factor," he said.

In the new study, Herzig's team went in search of components of that regulatory machinery that might be important in the case of fatty liver disease, a condition that is tightly associated with several components of metabolic syndrome, including diabetes and heart disease.

"Fatty liver may be one reason for the further development of insulin resistance. It appears to contribute to some of the long-term complications and is an independent risk factor for cardiovascular complications," said Herzig.

The researchers looked to mice with fatty liver disease of various genetic or dietary causes. In every case, those mice also showed impaired activity of TBL1 in the liver.

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When the researchers disabled TBL1 in the livers of healthy mice, they too went on to show high triglycerides and the buildup of fat in the liver.

In human patients, TBL1 levels were also inversely related to the amount of fat in an individual's liver. In other words, as TBL1 levels go down, it appears that liver fat levels go up.

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The study appeared in the April issue of Cell Metabolism, a Cell Press publication.

Source-ANI