Harvard doctors have overturned long-held ideas about obesity, diabetes and heart disease

Insulin resistance is an important risk factor for diabetes, which occurs when the body's cells do not respond to insulin and cannot use glucose (sugar) in the blood
.
This condition is associated
with an increased risk of cardiovascular disease and atherosclerosis.
Atherosclerosis refers to the accumulation of fat in the arteries, which restricts blood flow to body tissues
.
However, the exact mechanism by which insulin interacts with the cells of the vessel wall is unknown
.

In a paper published in Circulation Research, scientists at the Jocelyn Diabetes Center describe a series of studies
designed to investigate the link between insulin, fat and the vascular system.
The research team, led by Dr.
George King, chief scientific officer and research director at Jocelyn University, has discovered an entirely new approach whereby the body's metabolism is controlled
by endothelial cells on blood vessels.
The findings challenge scientific dogma that vascular dysfunction may be the root cause of adverse metabolic changes leading to diabetes, contrary to previous belief
.

"In patients with diabetes and insulin resistance, white fat and inflammation have long been thought to cause vascular dysfunction that contributes to the prevalence of heart disease, eye disease and kidney disease in these patients," said
Thomas J.
Beatson, Jr.
, professor of medicine in the field of diabetes at Harvard Medical School.
"But we found that blood vessels can play a major control role here, which was not known before
.
"

In addition to vascular problems, diabetes is also associated
with an undesirable reduction in the body's storage of brown fat, also known as brown adipose tissue.
Unlike white fat, brown fat burns energy, regulates body weight and metabolism, and maintains body temperature
.
King and his colleagues found that in a series of tests using a mouse model of diabetes, the genetically modified mice only increased insulin sensitivity in their blood vessels, and even when given a high-fat diet, they weighed less
than the control animals.
The study found that mice that were particularly sensitive to insulin had more brown fat than those in the control group, and that vascular damage was reduced
.

Further research by the team found that insulin signals vascular endothelial cells to produce nitric oxide, which in turn triggers the production
of brown fat cells.
In the case of insulin resistance, endothelial cells produce less nitric oxide — a reduction known to increase cardiovascular risk — leading to a decline in
brown fat production.
Because brown fat plays an integral role in regulating body weight and metabolism, less brown fat storage may be a risk factor for diabetes rather than a symptom of
diabetes.

King said: "We found here that endothelial cells in the lining of blood vessels have an important control role
in the formation of brown fat.
The discovery that nitric oxide comes from endothelial cells and is used to regulate the production of brown fat is very exciting because in the past we thought diabetes would cause cardiovascular problems, but in this case, the relationship seems to be reversed
.
”

The study's findings set the stage for using brown fat and the hormones and inflammatory proteins it controls as biomarkers, or markers that doctors can detect, for atherosclerosis or cardiovascular disease
.
In future animal and clinical studies, this new information may open the door to a whole new approach to weight control that increases brown adipose tissue
by increasing endothelial cell nitric oxide production.

"Everything is interconnected," King said
.
"We believe that blood vessels and endothelial cells play an important role not only in regulating brown fat, but also in regulating metabolism throughout the body
.
As a result, these endothelial cells are key in regulating weight and developing diabetes, and as other labs have shown, blood vessels also appear to be the main regulators of
brain function.
Intervention at the endothelial cell level can have a significant impact on
many diseases.
”

Reference: Endothelial cells induced progenitors into brown fat to reduce atherosclerosis