A study of Salk Institute has identified a new protagonist in the development of atherosclerosis, a frequent cause of cardiovascular diseases: sphingolipids, a type of lipid that, like cholesterol, contributes to the formation of arterial plaques and increases the risk of serious events such as accidents. cerebrovascular accidents and heart attacks. Posted in ‘Cell Metabolism‘, this finding opens new therapeutic possibilities to combat these conditions.
For years, trans fats have been linked to increased cardiovascular risk, but attention has primarily focused on their impact on cholesterol levels. However, this new study highlights how these fats, processed by an enzyme called SPT, are incorporated into sphingolipids in the liver. This causes excessive secretion of harmful lipoproteins (such as VLDL) into the bloodstream, contributing to the formation of atherosclerotic plaques.
The researchers conducted an experiment on mice fed diets rich in trans or cis fats, but low in cholesterol. The results showed that trans fats, unlike cis fats, favor the accumulation of harmful sphingolipidsleading to an increase in arterial plaques, fatty livers and insulin resistance. On the contrary, cis fats, present in natural foods such as fish or nuts, generated less harmful effects, limited to short-term weight gain.
The research focused on the SPT enzyme, key in the synthesis of sphingolipids from fats and amino acids such as serine. By inhibiting this enzyme in animal models, scientists were able to significantly reduce the formation of trans fat-induced atherosclerotic plaques, pointing to SPT as a crucial target for future treatments.
“The fat in our diet has a profound impact on our health, and we now better understand how sphingolipid metabolism contributes to cardiovascular risk,” explains Professor Christian Metallostudy leader. “Our findings may lead to new therapies that go beyond traditional statins, opening paths towards more personalized and effective medicine.”
Despite the efforts of the World Health Organization to eliminate trans fats from foods, almost 4 billion people will still be exposed to their harmful effects in 2024 due to failure to follow best practices. This study highlights the importance of new strategies to combat cardiovascular disease in people who are still at risk.
The team also plans to investigate a specific subunit of the SPT enzyme, suspected of selectively expelling dangerous lipids from the liver. This approach could lead to the development of innovative drugs capable of preventing and treating ASCVD without relying exclusively on cholesterol control.
With these advances, researchers hope to transform the treatment of cardiovascular diseases, offering cholesterol-free alternatives that target sphingolipid metabolism. These findings represent a crucial step towards more effective therapies tailored to the needs of each individual.
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