A group of scientists explain a series of tests meant to uncover the link between insulin, lipids, and the vascular system, and they discovered a new mechanism in which endothelial cells, which line blood arteries, influence the body’s metabolism.
The findings were reported in the journal Circulation Research. In a reversal of scientific paradigm, the findings show that vascular dysfunction, rather than being an outcome, may be the cause of adverse metabolic alterations that might lead to diabetes.
“In people with diabetes and insulin resistance, the idea has always been that white fat and inflammation causes dysfunction in the blood vessels, leading to the prevalence of heart disease, eye disease and kidney disease in this patient population,” said King, the Thomas J. Beatson, Jr. Professor of Medicine in the Field of Diabetes at Harvard Medical School. “But we found that blood vessels can have a major controlling effect here, and that was not known before.”
Diabetes is connected with an unwanted decrease in the body’s storage of brown fat, often known as brown adipose tissue, in addition to blood vessel problems. Brown fat, as opposed to white fat, consumes energy, regulates body weight and metabolism, and maintains body temperature. King and colleagues discovered that mice altered with heightened insulin sensitivity exclusively in the blood vessels weighed less than control animals, even when fed a high-fat diet, in a series of tests with a mouse model of diabetes. The additional insulin-sensitive mice were found to have more brown fat than control animals, as well as reduced blood vessel damage.
Further research demonstrated that insulin signals endothelial cells in blood arteries to create nitrous oxide, which then stimulates the formation of brown fat cells. Endothelial cells produced less nitrous oxide in the context of insulin resistance, a reduction known to increase cardiovascular risk, leading to a decrease in brown fat formation. Because brown fat is so important in controlling the body’s weight and metabolism, lower brown fat deposits may be a risk factor for diabetes rather than a symptom of it.
“What we found here is that the endothelial cells lining the blood vessels can have a major controlling effect on how much brown fat you develop,” said King.
“Nitrous oxide comes from endothelial cells to regulate how much brown fat you make, and that finding is very exciting because in the past we thought diabetes causes cardiovascular problems, but that relationship appears to be reversed in this scenario,” he added.
The study’s results pave the way for doctors to employ brown fat and the hormones and inflammatory proteins it regulates as biomarkers for atherosclerosis or cardiovascular disease. This new discovery might pave the way for an altogether new strategy of weight control by expanding brown fat tissues through improved endothelial nitrous oxide production in future animal and clinical research.
“Everything is connected,” said King.
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“We think blood vessels and endothelial cells play an important role not just in regulating brown fat, but also in regulating the whole body’s metabolism. Thus, these endothelial cells are a key factor in regulating weight and developing diabetes and, as other labs have shown, blood vessels appear to be a major regulator of brain function as well. Intervening at the level of endothelial cells could have a major impact on many diseases,” he concluded.
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