Stop the development of diabetes
A group of researchers changed the course of diabetes by inactivating the enzyme dihydroceramide desaturase 1 (DES1). This prevented him from removing the final hydrogen atoms from the ceramide lipid and led to a decrease in the total amount of ceramides in the body. The DES1 enzyme is a potential target for the development of new treatments for common diseases (prediabetes, diabetes, cardiovascular diseases).
Ceramide plays an important role in metabolism: the authors compare this lipid with cholesterol in importance – a decrease in ceramide levels can reverse the signs of diabetes and other metabolic diseases.
The researchers tested the hypothesis on adult genetically modified mice by blocking the final stage of ceramide synthesis: they turned off the gene encoding DES1 in the tissues of the entire body or only in the liver or fat cells. To selectively reduce DES1 production by destroying the RNA precursor, a short hairpin of RNA was injected into the adult liver.
At first, the mice were given a feed with a high fat and carbohydrate content, similar in composition to a shortbread dough, six times higher than the fat content of the usual rodent diet. The mice gained twice their weight in three months. They developed insulin resistance and accumulated fat in the liver – these are signs of a metabolic disorder. The researchers then reduced the synthesis of ceramides and observed significant changes for several weeks. The mice remained obese, but became healthy. Metabolism was restored: fat was gradually excreted from the liver, sensitivity to insulin and glucose increased. The mice remained healthy for two months. The long-term consequences are currently being investigated.
In another experiment, the level of ceramides was lowered before mice began to receive high-calorie food. This tactic prevented weight gain and the development of insulin resistance.
The effect of the reduction of ceramides on human health is still unknown, but the results obtained indicate their connection with metabolic disorders. Perhaps screening tests for ceramides will help calculate the risk of developing diabetes or heart failure.
The group is currently developing drugs that inhibit DES1, with the aim of creating a new drug against diabetes.
"Bad" ceramides
The researchers found that ceramides trigger a number of mechanisms that contribute to the accumulation of fat in cells, as well as impair the ability of cells to use glucose as fuel. This happens as a result of activation of the Akt/PKB molecular pathway, which inhibits both the ability of cells to synthesize sugars and to remove them from the bloodstream. In addition, ceramides partially slow down lipid metabolism, causing liver cells to increase the accumulation of fatty acids, and adipose tissue to burn less fat.
One of the advantages of ceramides is that they strengthen the cell membrane and protect the cell. When a lot of fat accumulates in the cells, an increase in the level of ceramides helps to strengthen the outer membrane and prevent ruptures. But with a chronic overabundance of lipids, for example, with obesity, the level of ceramides is constantly increased. This leads to a decrease in insulin sensitivity and fatty degeneration of the liver.
Thus, ceramides are a protective mechanism during overeating, helping the body cope with a situation when the amount of fat entering the cells exceeds its energy needs and the ability to accumulate.
Article by B. Chaurasia et al. Targeting a ceramide double bond improves insulin resistance and hepatic steatosis is published in the journal Science.
Aminat Adzhieva, portal "Eternal Youth" http://vechnayamolodost.ru according to Eurekalert: Tiny change has big effects, reverses prediabetes in mice.