How does overeating lead to diabetes? A wave of neurotransmitters

Obese people are ten times more likely to develop diabetes than lean people. Researchers trying to understand why have found an answer in the same system that controls the body’s fight-or-flight response. The findings¹In mice, you’re challenging long-held assumptions about how eating too much can make you sick.

The study suggests that consuming a high-fat diet causes a surge of neurotransmitters throughout the body, leading to the rapid breakdown of fatty tissue in the liver – a process normally controlled by the release of insulin. The release of high levels of fatty acids is linked to a host of health problems, from diabetes to liver failure².

Stem cells reverse diabetes in women – a world first

Researchers previously thought that the biggest problem is caused by obesity diabetes there was a lack of insulin activity, which means that the body cannot stop the dangerous release of fatty acids. But “rather than the breaks not functioning,” the latest study finds that there is a separate lever – neurotransmitters in the liver and other tissues – pushing hard on the accelerator, says Martina Schweiger, a biochemist at the University of Graz, Austria. “This is indeed a paradigm shift.”

The research was published in Cell metabolism on October 21.

Insulin resistance

More than 890 million people worldwide have this obesitythat’s a important risk factor for developing diabetes and other metabolic disorders. Researchers have long known that the disease progresses when insulin stops lowering glucose levels in the blood. Christoph Buettner and Kenichi Sakamoto, both physiologists at Rutgers University in New Brunswick, New Jersey, and their colleagues wanted to better understand the nature of this insulin resistance.

Buettner has long studied the role of insulin in the brain in regulating metabolism³So he and his team turned their attention to the sympathetic nervous system, which delivers neurotransmitters such as norepinephrine to tissues throughout the body. The researchers used a mouse model they had previously developed in which they deleted a gene that expresses a key enzyme needed to produce these neurotransmitters. The gene was deleted only in the mouse’s limbs and some organs, not in the brain, to ensure the mouse’s survival.

The researchers gave the modified mice a diet rich in fats such as lard, coconut oil and soy oil. Over more than two months of observation, both modified and unmodified mice ate the same amount of food, gained weight in similar amounts, and maintained similar insulin signaling activity, which is the cascade of events that occurs after insulin binds to its target receptor on a cell. .

But the modified mice did not show increased breakdown of fat tissue and insulin resistance and ultimately did not show increased signs of fatty liver disease and tissue inflammation. The unmodified mice, on the other hand, developed insulin resistance, which can lead to diabetes. They also showed increased signs of inflammation and liver disease.

Signals in the brain

The findings suggest that neurotransmitters are responsible for causing insulin resistance and its associated problems, Buettner says. He and his colleagues are now investigating the role of these neurotransmitters in other conditions, such as insulin resistance caused by menopause.

“This study is pretty solid,” says Schweiger, but “there are still some pieces of the puzzle missing.” The question now, for example, is how the high-fat diet causes the increase in neurotransmitters, she says.

She also says more work is needed to better understand the implications of the findings for people. So far, drugs that block the activity of neurotransmitters involved in the sympathetic nervous system have not provided benefits in people with obesity. It’s possible that targeting these drugs to specific tissue and avoiding the brain could be more promising, Buettner says.