Severe Diabetes may be Cured by Restoring Leptin Sensitivity in Brain

Restoring leptin sensitivity to a tiny area of POMC neurons in the brain's hypothalamus cures mice deficient in the leptin-receptor of severe diabetes

Restoring leptin sensitivity to a tiny area of POMC neurons in the brain's hypothalamus cures mice deficient in the leptin-receptor of severe diabetes, according to a study by scientists at Beth Israel Deaconess Medical Center (BIDMC).

Writing about their findings in the journal Cell Metabolism, the researchers say that their findings may help further expand the understanding as the leptin's role in the brian's complex neurocircuitry behind weight gain and glucose control.

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"This discovery suggests a new therapeutic pathway for drugs to treat insulin-resistant diabetes in humans with severe obesity, and possibly even to stimulate their urge to exercise," says Dr. Christian Bjorbaek, a researcher in the Division of Endocrinology, Diabetes and Metabolism at BIDMC and Associate Professor of Medicine at Harvard Medical School.

"We know that the majority of humans with Type 2 diabetes are obese and that weight loss can often ameliorate the disease. However, in many cases, it's difficult for these individuals to lose weight and can keep weight off. If, as these findings suggest, there is a system in the brain that can control blood-glucose directly, it offers hope for the identification of novel anti-diabetic drug targets," Bjorbaek added.

Leptin, which was first identified in 1994 as an appetite and weight-regulation hormone, is known to play a key role in energy homeostasis through its effects on the central nervous system.

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Previously conducted studies have already shown that a region of the brain's hypothalamus, known as the arcuate nucleus (ARC), is one key area where leptin exerts its influence.

Within the ARC, scientists have also identified two types of leptin-responsive neurons: the Agouti-related peptide (AgRP) neurons, which stimulate appetite and the pro-opiomelanocortin (POMC) neurons, which curb appetite.

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"Still other studies had indicated that, by way of the ARC, leptin also had a function in both blood-sugar control and in activity levels. We hypothesized that, in both cases, the POMC neurons were involved," says Bjorbaek.

He reveals that with a view to testing their hypothesis, the research team studied a group of leptin-receptor-deficient laboratory mice.

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"The animals were severely obese and profoundly diabetic. Using Cre-Lox technology we were able to genetically and selectively re-express leptin receptors only in the POMC neurons. When leptin receptor activity was restored to just this very small group of neurons, the mice began eating about 30 percent fewer calories and lost a modest amount of weight," he says.

Bjorbaek further reveals that the animals' blood sugar levels returned to normal independent of any change in weight or eating habits, and their activity levels spontaneously doubled.

The researcher concedes that more studies are required to explain the mechanisms at play.

Source-ANI
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