Targeting the LEAP2-Ghrelin System in Chronic Conditions
Introduction to Ghrelin
A recent article in Science highlights the potential of targeting the LEAP2-ghrelin system as a therapeutic approach for chronic conditions like obesity and diabetes. Ghrelin, commonly known as the “hunger hormone,” was first identified by researchers two decades ago. Initially, it was believed that blocking ghrelin could suppress appetite and promote weight loss. However, studies focusing solely on ghrelin did not yield the expected results.
Renewed Interest in Ghrelin
After twenty years, ghrelin has regained attention. Researchers in California have discovered that indirectly targeting the ghrelin pathway may provide a means to manage conditions such as diabetes and obesity. Their study focused on the genetic changes following a stomach-reduction procedure in obese mice, a method often used in humans for weight control. Among the identified genes, one notable gene encodes LEAP2, a protein produced in the liver and small intestine. The stomach-reduction procedure resulted in a remarkable 52-fold increase in LEAP2 expression.
LEAP2 and Ghrelin Interaction
This significant increase led researchers to further investigate the relationship between LEAP2 and ghrelin. The studies revealed that LEAP2 can inhibit ghrelin activity. Ghrelin plays a role in stimulating glucose production, which helps maintain blood sugar levels during periods of low food intake. When ghrelin was administered to starved mice, there was an increase in glucose production, which was suppressed when LEAP2 was introduced.
Further Confirmation of LEAP2’s Role
To solidify their findings, the researchers created mice that overproduced LEAP2. After a week on a low-calorie diet, these mice exhibited significantly low blood glucose levels, confirming LEAP2’s ability to inhibit glucose synthesis induced by ghrelin.
Implications for Treatment
The implications of these findings are substantial. One immediate possibility is the regulation of blood glucose levels in diabetic patients by blocking LEAP2’s inhibitory effect on ghrelin. Additionally, researchers believe that targeting LEAP2 could also aid in combating anorexia and obesity. Many individuals who lose weight often regain it due to increased appetite, potentially driven by elevated ghrelin levels. There is potential for LEAP2 to act as an appetite suppressant by reducing ghrelin levels.
The Need for Further Research
While the prospects of utilizing LEAP2 to manage chronic diseases are promising, extensive research is necessary to fully understand ghrelin’s role in these conditions. Only with a clearer understanding of these mechanisms can scientists consider targeting molecules like LEAP2 as viable treatment options.
Written by Natasha Tetlow, PhD
Reference: Leslie, Mitch. Gut molecule that blocks ‘hunger hormone’ may spur new treatments for diabetes, anorexia. Science Health. 2017. Available at: doi:10.1126/science.aar6974.