Research challenges belief that high ceramide levels cause heart disease

Research rejects the conventional belief that high levels of ceramides cause cardiovascular diseases in obesity and diabetes patients. Instead, suppressing this type of fat in the lining of blood vessels causes damage and chronic illness, argue researchers at Weill Cornell Medicine, US.

When ceramide breaks down in the body, it produces sphingosine-1-phosphate (S1P). The researchers found that two proteins, Nogo-B and ORMDL, decreased the production of ceramides and SP1 in obesity. This increased blood pressure, impaired vascular regulation, and raised glucose levels.

Targeting this metabolic pathway could have multiple beneficial effects in treating cardiometabolic diseases related to obesity, the researchers suggest.

“Recent data show that >1.6 billion people worldwide are overweight or obese, a condition causally linked to diabetes, non-alcoholic liver steatosis, and cardiovascular disease,” notes the paper.

“Endothelial dysfunction is an early event in the onset of cardiometabolic diseases, including diabetes, obesity, and atherosclerosis, and emerging studies have shown that it can also enhance metabolic dysregulations.”

Importance of ceramides

The study explains that ceramides are naturally found in the body and function to regulate blood vessel tone and dilate or contract vessels to control blood pressure. They help prevent blood clots and enable blood’s easy flow.

The research team previously found that ceramides increase as a protective response in a mouse model of coronary artery disease.

Dr. Annarita Di Lorenzo, professor of pathology and laboratory medicine at Weill Cornell Medicine, comments: “Ours is the first in vivo study that measures the levels of the lipids in the endothelial cells of an animal model. In obese mice fed a high-fat diet, ceramides do not build up — they decrease compared to lean mice.”

Targeting ceramide’s metabolic pathway could have multiple beneficial effects in treating cardiometabolic diseases related to obesity, the researchers suggest.According to a different study, dietary interventions that are beneficial in regulating ceramide levels include the Mediterranean diet, lacto-ovo-vegetarian diet, calorie-restricted diet, limiting the consumption of dairy products, and dietary supplements that contain polyunsaturated fatty acids, dietary fibers, and polyphenols.

Metabolic activity opens new solutions 

The study published in Nature Communications shows that removing Nogo-B proteins in blood vessels in obese mice improved blood vessel health.

Lorenzo comments: “By knocking out this inhibitor, we preserved vascular health. This also showed that regulating ceramide metabolism causes vascular dysfunction and inflammation in obesity.”

“These mice have the same body weight and diabetes as controls, but their blood vessel health is much better.”

The paper suggests that targeting this metabolic pathway could provide new solutions to treat cardiometabolic obesity-related diseases.