Targeting the body’s ceramide chemistry in an exceedingly refined method may lead to the event of safe new treatments for kind two polygenic disease, cardiovascular disease, and different metabolic conditions.
This was the suggestion that scientists created when finding that they may reverse prediabetes in mice with blubber by silencing associate degree protein answerable for the ultimate step of ceramide production.
Deactivating the protein, known as dihydroceramide desaturase one (DES1), lowered levels of ceramide within the body, they note in an exceedingly recent Science paper concerning their work.
Switching off DES1 additionally prevented mice on a high fat diet from developing liver disease and internal secretion resistance. These 2 conditions ar prime risk factors for cardiovascular disease and polygenic disease.
DES1 controls the conversion of dihydroceramide into ceramide with alittle chemical shift of 2 element atoms. This refined alteration effectively inserts a “double bond into the backbone” of the lipoid molecule.
Previous investigations had already urged that reducing ceramide levels might probably reverse metabolic malady and polygenic disease. However, the ways that they used would end in severe facet effects.
Ceramides because the next cholesterol’
The new study takes the analysis in an exceedingly splendid therapeutic direction. It suggests that it may well be attainable to scale back ceramide levels in an exceedingly safe method with alittle, well regular tweak to the method of ceramide production.
“Our work,” says co-senior study author faculty member. Scott A. Summers, department chair of Nutrition and Integrative Physiology at the University of American state in Salt Lake town, “shows that ceramides have associate degree important role in metabolic health.”
“We’re thinking of ceramides because the next sterol,” he adds.
Scientists ar still sorting out however lowering the ceramides affects the body. However, there’s proof, Prof. Summers argues, of a link between ceramides and metabolic malady.
He says that some doctors ar already effecting tests of ceramide levels as the way to assess people’s risk for cardiovascular disease.
“Ceramides contribute to the lipotoxicity that underlies polygenic disease, internal organ steatosis [fatty liver], and cardiovascular disease,” note the authors of the new study.
If ceramides is a reason behind malady, what purpose do they serve within the body? The researchers investigated this question by assessing the impact of ceramide on metabolism.
Ceramide professionals and cons
In a 2013 study into DES1 and ceramides, Prof. Summers and his co-authors mentioned however blubber might increase metabolic malady risk, and the way ceramides contribute.
The theory is that in folks with blubber, the body’s tissues receive associate degree abundance of lipids that they can’t store, and this ends up in a buildup of “fat-derived molecules that impair tissue perform.”
Prof. Summers and his colleagues discovered that ceramides depart variety of processes that increase fat storage in cells. additionally, they disrupt the power of cells to urge energy from sugar, or glucose.
The lipids additionally block the process of fatty acids. they are doing this in 2 ways: by obtaining the liver to store additional fatty acids, and by reducing fat burning in tissues.
Ceramides even have different functions. one in all these is to strengthen cell walls.
Prof. Summers so suggests that as a result of increasing fat storage raises ceramide levels, it might appear that ceramides have a job in protective cells from rupturing throughout times of masses, once the body will increase its fat stores.
However, within the case of blubber, ceramide seems to require on the role of a cyanogenetic lipoid.
Obese mice had improved metabolic health
In the recent study, the researchers lowered ceramide levels in mice by move off the last step of ceramide synthesis. To accomplish this, they sequencetically designed mice within which they may cut the gene for DES1 in adult animals.
They developed 2 ways that of change off DES1: globally and by selection. within the international approach, they silenced DES1 within the whole body. within the selective approach, they shifted the protein in selective locations, like within the liver or fat cells.
When they shifted DES1 to lower ceramides in very weighty mice with internal secretion resistance and liver disease, they found that either approach worked. The animals’ metabolic health improved, although they remained weighty.
Their livers got eliminate fat, and their internal secretion and aldohexose responses were as sharp as those of healthy, lean mice. when two months of observation, the animals remained in physiological condition.
Prof. Summers explains that though the mice failed to shed any weight, their bodies had modified the method that they processed nutrients.
In another set of experiments, the team found that reducing ceramide levels before putting the mice on high fat diets stopped the animals from gaining weight and developing internal secretion resistance.