What if the problem is not limited to cholesterol? In summary, what if different streams of fatty acids combine in the blood flow, triggering distinct chronic or acute pathologies?
Excess cholesterol is now well known to form artery-clogging plaques (atheroma) which can lead to stroke, arterial disease, heart attack, etc. This new research deciphers how another class of lipids, sphingolipids, also contributes to arterial plaques and atherosclerotic cardiovascular diseases.
Another “source” of cardiovascular disease in addition to cholesterol
The study The longitudinal study is carried out on mice fed a high-fat diet, without additional cholesterol addition, and follows the circulation of these fat flows in the models' bodies. The analysis reveals that:
- the progression of atherosclerotic cardiovascular disease induced by high trans fats is promoted by certain trans fats in ceramides and by other sphingolipids;
- the discovery that sphingolipids promote the formation of atherosclerotic plaques reveals another “source” of cardiovascular disease in addition to cholesterol.
What processes? When dietary fats enter the body through the foods we eat, they must be sorted and transformed into compounds called lipids, such as triglycerides, phospholipids, cholesterol or sphingolipids. Lipoproteins, such as the famous HDL (high density lipoproteins or “good cholesterol”), LDL (low density lipoproteins or “bad cholesterol”) and VLDL (very low density lipoproteins or very low density lipoproteins). low density), are used to transport these lipids in the blood.
Sphingolipids have become useful biomarkers for diseases such as atherosclerotic cardiovascular disease, nonalcoholic fatty liver disease, obesity, diabetes, peripheral neuropathy, and neurodegeneration. However, it is unclear how the incorporation of different dietary fats into sphingolipids leads to the development of atherosclerotic cardiovascular disease.
The fate of dietary fat is often determined by the protein that metabolizes them. The team therefore explored the “metabolic landscape” that allows the production of sphingolipids:
- a protein, SPTacts as a valve to regulate the synthesis of sphingolipids from fat molecules and amino acids, such as serine;
- trans fats are incorporated into sphingolipids by SPT;
- this promotes the excessive secretion of lipoproteins into the blood circulation, which then promotes the development of atherosclerotic cardiovascular disease;
- the incorporation of trans fats through the SPT protein further increases the secretion of lipoproteins by the liver, which accelerates the formation of atherosclerotic plaques;
- Sphingolipid metabolism is therefore a key factor in the progression of cardiovascular diseases induced by specific dietary fats.
By gradually identifying the different molecules circulating in our body that are involved in the progression of atherosclerosis, it becomes possible to broaden the treatment options.
A completely new therapeutic approach must therefore open with this study: the main author, Dr. Christian Metallo, professor of metabolism at Salk, specifies here: “Fats make up an important part of our diet, and the consumption of trans fats is known to promote cardiovascular disease. Many studies have been conducted on how trans fats promote cardiovascular risk, but it always comes back to cholesterol. By looking at the question from another angle, without considering cholesterol as a factor, we identify an enzyme (SPT) and a pathway linked to cardiovascular diseases that we can add to our therapeutic targets..
