The Satiety Hormone Leptin Plays a Crucial Role in the Development of Type 2 Diabetes

Impaired transport of the hormone leptin contributes to impaired insulin secretion and contributes to the development of diabetes.

Diabetes

Leptin, also known as the satiety hormone or appetite-suppressing hormone, is a hormone secreted by adipocytes (fat tissue). Its role is to regulate appetite by controlling satiety. In a new study published on Monday 2 August in the journal Nature Metabolism, researchers from the French institute Inserm discovered that its deregulation alters insulin secretion and contributes to the development of diabetes.

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Without the receptor LepR, fat mass increases

Leptin is transported to the brain by cells called tanycytes, to which it binds through receptors called LepR. It is through this process that the hormone is able to cross the blood-brain barrier and transmit a sense of satiety to neurons. Previous studies have shown that it is this transport to the brain that is impaired in overweight or obese people and that this partly explains the disturbances in appetite regulation.

In this new study, researchers have investigated the role of LepR receptors. They observed in mouse models what happens when these receptors are absent. After three months, they found that the mice’s fat mass had doubled, while their muscle mass had halved.

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Reduced leptin transport is linked to the development of type 2 diabetes

The researchers also noted that in order to maintain normal blood sugar levels, the mice secreted more insulin during the first four weeks of the experiment. Three months after the receptor was removed, their ability to secrete pancreatic insulin was exhausted. These characteristics indicate that the mice developed a pre-diabetic state. In the long term, the mice are no longer able to secrete insulin and thus control the amount of glucose in their blood,” the researchers confirm. These data, therefore, suggest that impaired transport of leptin through LepR receptors in the brain is associated with the development of type 2 diabetes.”

Normally, blood glucose rises after glucose intake and then falls back to help it enter the body’s cells. Without the LepR receptor, blood glucose is abnormally high during fasting and rises again after glucose intake. This makes the pancreas unable to release the insulin it needs and it becomes dysfunctional.

Leptin is essential for the brain

As a final step, the researchers reintroduced leptin into the brain to monitor the body’s response. This caused an immediate restoration of the pancreas’ activity, which immediately restored the ability to secrete insulin to regulate blood sugar. This allowed the mice to regain a healthy metabolism.

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“We showed that leptin perception in the brain is crucial for controlling metabolic homeostasis and blood glucose levels. On the other hand, when leptin transport to the brain is blocked, the correct functioning of the neurons that control insulin secretion in the pancreas is altered,” he said. concludes Vincent Prévot, Inserm’s research director and the study’s lead author.

The results of this study will open another avenue for the treatment and prevention of diabetes.

References

Leptin brain entry via a tanycytic LepR–EGFR shuttle controls lipid metabolism and pancreas function