The research team found out that metabolic disease affects blood vessels in different organs of our body in a unique way. For instance, blood vessels in the liver and fat tissue struggle to process the excess lipids, kidney vessels develop metabolic dysfunction, lung vessels become highly inflammatory, and transport across the brain vessels is defective.
“As vascular dysfunction drives all major pathologies, from heart failure to atherosclerosis and neurodegeneration, our research shows how bad eating habits molecularly promote the development of diverse diseases,” explains the first author of the study.
“We want to elucidate molecular mechanisms of obesity in order to be able to offer patients tailor-made therapies in the future,” adds the senior author.
The researchers then asked whether a healthy diet could reduce the disease-causing molecular signatures induced by a bad diet. Their results show that a healthy diet can indeed improve the molecular health of blood vessels, albeit only partially.
They find that obesity deregulates gene expression networks, including lipid handling, metabolic pathways and AP1 transcription factor and inflammatory signaling, in an organ- and EC-subtype-specific manner. The transcriptomic aberrations worsen with sustained obesity and are only partially mitigated by dietary intervention and weight loss.
For instance, the blood vessels in the liver recovered nearly completely, but blood vessels in the kidneys retained the disease signature, despite a healthy diet and significant weight loss. This means that some of our blood vessels can develop a “memory” of metabolic disease, which is difficult to reverse.
Organ-specific vulnerabilities of blood vessels in obesity
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