Amazing stuff!
"The study ... challenges the conventional belief that ceramides, a type of fat, accumulates in blood vessels causing inflammation and health risks. Instead, their findings reveal that when ceramides decrease in endothelial cells lining blood vessels, it can be damaging and cause chronic illnesses. Ironically, the findings could ultimately lead to therapies that maintain high levels of these protective lipids in patients with obesity. ...
In obese mice fed a high-fat diet, ceramides do not build up – they decrease compared to lean mice. ...
Ultimately, when ceramide is broken down by the body it produces a compound called sphingosine-1-phosphate (S1P), which builds up and protects mice against cardiovascular disease. But when this process doesn’t work the mice are left vulnerable.
The researchers also found that two proteins, Nogo-B and ORMDL, decreased the production of ceramides and S1P in obesity. This decrease leads to increased blood pressure, impaired vascular regulation and higher glucose levels – all of which contribute to cardiometabolic conditions that affect the heart (cardiovascular system) and energy processing (metabolism), like diabetes like diabetes, hypertension, coronary artery disease and stroke. ..."
From the abstract:
"Accrual of ceramides, membrane and bioactive sphingolipids, has been implicated in endothelial dysfunction preceding cardiometabolic diseases. Yet, direct in vivo evidence, underlying mechanisms, and pathological implications are lacking.
Here we show that suppression of ceramides and sphingosine-1-phosphate (S1P), a product of ceramide degradation, are causally linked to endothelial dysfunction and activation, contributing to vascular and metabolic disorders in high fat diet fed (HFD) male mice.
Mechanistically, the upregulation of Nogo-B and ORMDL proteins suppress ceramide de novo biosynthesis in endothelial cells (EC) of HFD mice, resulting in vascular and metabolic dysfunctions.
Systemic and endothelial specific deletion of Nogo-B restore sphingolipid signaling and functions, lowers hypertension, and hepatic glucose production in HFD.
Our results demonstrate in vivo that ceramide and S1P suppression rather than accrual contributes to endothelial dysfunction and cardiometabolic diseases in HFD mice. Our study also sets a framework for the development of therapeutic strategies to treat these conditions"
Fig. 7: The inhibition of ceramide de novo biosynthesis by Nogo-B in HFD mice results in the suppression of both ceramide and S1P, contributing to vascular and metabolic disorders.
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