Scientists identify gene essential for normal liver metabolism

As obesity increases a growing need for fat in the body becomes more of an issue. As people become overweight and obese they are at greater risk of developing diabetes insulin resistance and liver failure. But it is still unclear why these diseases develop at the same time that the liver becomes thinner. Researchers at Karolinska Institutet in Sweden have now found a possible answer: genes that are essential for the healthy liver metabolism. The study is published in the journal Cell Metabolism.

Liver fatty liver disease is a common problem that has been seen in different ethnic groups and can present suddenly after a few weeks living with a low-fat diet. Scientists do not yet understand the exact relationship between obesity and liver fat but they do know that the fat in the liver is not transferred from the fat tissue to the bloodstream and therefore fat in the liver is not only the source of unpleasant or unpleasant effects but also a major cause of obesity-related diseases.

Liver inflammation has been linked to obesity-related diseases. As a result people cannot flush the excess fat out of the body even when they have enough energy. In obese individuals the liver has a high production of glucose by a type of cells called glomerular cells-a hormone called lactate-that are usually lacking in the liver. During periods of fasting it is possible for the body to find ways to flush the excess glucose through the blood. In most cases this fluid is pumped by the liver into the bloodstream where it flows back again under ketosis. It is thought that this happens with obese individuals on a high-fat diet but it does not occur in all people regardless of the body mass index.

Few studies have been performed yet in relation to the lactate problem in the liver. Interestingly some of the studies done on mice have reported positive changes in the blood vessels in the liver with greater lactate than in those without the condition. It has been unclear why things are this way in the liver but now an international team of researchers from Karolinska Institutet have identified a possible explanation: genes that are essential for normal liver metabolism.

The study was carried out on mice that were allocated to either a high- or low-fat diet. After two weeks the mice that were assigned the high-fat diet were given access to a high-fat staining diet. Mice that were also given the low-fat diet had access to the same diet for twice as long. In themselves mice on one of the high-fat diets showed more improvements in how their liver worked than mice on the low-fat diet. The mice participating in each diet pairing continued to eat the same way as before.

These changes in metabolic state of the liver can be easily translated into alterations in blood glucose and insulin resistance and we have already seen that these two factors can increase the risk of diabetes and insulin resistance in obesity says principal investigator Claudio Villaverde senior physician and researcher at the Department of Paediatric and Peripheral Medicine at Karolinska Institutet.

In summary the researchers have identified two genes that are essential for the nutritionally well-balanced liver metabolism in obese people: the genes ANC mediates to produce some amino acids and small glycemia enhancer knockout1 (LS1) that suppresses sugar production. The findings suggest that a reduction in the production of glucose could be beneficial-and in the case of a high-fat diet not the recommended amount this is particularly encouraging says Tyler McCross who carried out the study together with Villaverde.

What do the results mean for humans? Lactate levels naturally increase due to the regulation of satiety by the liver and there is no evidence that the reduction in lactate produced by the liver is directly related to a high-fat diet. Therefore the authors believe that the effects on metabolites including lactate may be different in humans. It is also possible that lower levels of lactate in the blood due to obesity may contribute to type II diabetes insulin resistance and metabolic problems. Our goal is simply to find out why humans seem to develop variations in metabolism in parallel with type I diabetes and type II diabetes says Torbjrn Magnusson doctoral student at the Department of Clinical Medicine at Karolinska Institutet who carried out the study (also principal investigator).